Advances in Novel Formulations for Drug Delivery E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
ADVANCES in NOVEL FORMULATIONS for DRUG DELIVERY The 27 chapters describe novel strategies for drug/nutraceutical delivery and embrace the development of formulations with herbal ingredients, while also highlighting disease therapeutics. Drug delivery technology has witnessed many advancements purported to cater to the customized needs of its ultimate beneficiaries--the patients. Today, dosage forms are not confined to conventional tablets, capsules, or injectables, but have evolved to cover novel drug carriers such as particulates, vesicles, and many others. Nanotechnological advancements have played a major role in this paradigm shift in ways of delivering active pharmaceutical ingredients. A new dimension in the use of food as medicine has also gained prominence in recent years. A portmanteau of nutrition and pharmaceuticals is "nutraceuticals," also known as functional foods and dietary supplements. The technologies which were earlier included in drug delivery have been attempted for the delivery of nutraceuticals as well. Herbal actives have received increased attention due to their low risk-to-benefit ratio. The field of drug delivery is quite dynamic in nature, as witnessed by its evolution from conventional dosage forms to nanotechnology-assisted drug products. A variety of formulations via different drug delivery routes have been developed to treat/cure/mitigate diseases or disorders. This book, comprising of 27 chapters, is a thorough compilation of information relevant to drug delivery systems with an emphasis on products based on nanotechnology. Audience Researchers, scientists, industry professionals, formulators and product developers, regulatory agencies in a variety of settings including novel drug delivery research laboratories, pharmaceutical, and pharmacy industries, biomedical sciences, food and nutraceuticals manufacturers, and nanotechnology.
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Table of Contents
Cover
Series Page
Title Page
Copyright Page
Preface
Part I: NOVEL DRUG CARRIERS AND THERAPEUTICS
1 Nanoarchitectured Materials: Their Applications and Present Scenarios in Drug Delivery
1.1 Introduction
1.2 Liposomes
1.3 Nanoparticles
1.4 Nanoemulsions
1.5 Dendrimers
1.6 Aquasomes
1.7 Nanogel
1.8 Quantum Dots
1.9 Carbon Nanotubes
References
2 Nanopharmaceuticals for Drug Delivery
2.1 Introduction
2.2 What Are Nanopharmaceuticals and What Do They Do?
2.3 Nanopharmaceuticals Importance
2.4 Nanotechnology
2.5 Pharmaceutical Companies and Nanotechnology
2.6 Applications and Advantages of Nanopharmaceuticals as Drug Carriers
2.7 Characteristics of Nanoparticles in Nanopharmaceuticals
2.8 Targeted Drug Delivery
2.9 Types of Nanoparticles
2.10 Nanoparticle Preparation Methods
2.11 Evaluation of Nanoparticles
2.12 Efficiency of Drug Entrapment
2.13 Particle Shape
2.14 Size of the Particles
2.15 Zeta Potential
2.16 Rise of Nanopharmaceuticals
2.17 Nanopharmaceuticals Approval Regulations (FDA Rules & Regulations)
2.18 Conclusions and Prospects for the Future
References
3 Applications and Prospects of Nanopharmaceuticals Delivery
3.1 Introduction
3.2 Nanopharmaceuticals
3.3 Development of Nanopharmaceuticals
3.4 Clinical Applications of Nanotechnology
3.5 Nanopharmaceuticals Delivery—Recent Applications
3.6 Nanotechnology in Neurodegenerative Disorders Treatment
3.7 Future Perspective
3.8 Issues with Current Nanopharmaceutical Concepts
3.9 Conclusion
References
4 Nanomedicine Regulation and Future Prospects
4.1 Introduction
4.2 Importance of Regulation of Nanomedicine
4.3 Regulatory Challenges Faced by Nanomaterial in Medicine
4.4 Nanomedicine Future Aspects
4.5 Challenges that Threaten the Future of Nanomedicine
4.6 Future Prospects for Nanomedicine
References
5 Nanotechnology Application in Drug Delivery for Medicinal Plants
5.1 Introduction
5.2 Nanoherbals
5.3 Conclusion
References
6 Nanosystems Trends in Nutraceutical Delivery
6.1 Introduction
6.2 Classification of Nutraceuticals
6.3 Biopharmaceutical Issues Associated with Nutraceuticals
6.4 Nanosystems for Delivery of Nutraceuticals
6.5 Challenges
6.6 Market Potential
6.7 Conclusion and Perspective
References
7 Nanoencapsulated Systems for Delivery of Phytopharmaceuticals
7.1 Introduction
7.2 Conclusions
References
8 Topical Drug Delivery Using Liposomes and Liquid Crystalline Phases for Skin Cancer Therapy
8.1 Introduction
8.2 Liposomes for Topical Application
8.3 Liquid Crystals and Liquid Crystalline Nanodispersions for Topical Application
8.4 Physical Methods Applied to Nanoparticles Delivery
8.5 Conclusions and Perspectives
Acknowledgements
References
9 Vesicular Drug Delivery in Arthritis Treatment
9.1 Introduction
9.2 Skin Penetration Pathways
9.3 Principles of Drug Permeation Through Skin
9.4 Problems Associated with Conventional Dosage Forms
9.5 Novel Treatment Strategies for Arthritis
9.6 Conclusion and Future Perspectives
References
10 Perspectives of Novel Drug Delivery in Mycoses
10.1 Introduction
10.2 Role of Conventional Drugs in Antifungal Therapy
10.3 Mechanism of Action of Conventional Antifungals
10.4 Summary of Nanoparticles and Their Role in Antifungal Therapy
10.5 Other Drug Delivery Systems
10.6 Conclusion
References
11 Nano-Based Drug Delivery in Eliminating Tuberculosis
11.1 Introduction
11.2 Antitubercular Therapy
11.3 Therapies Based on Nanotechnology
11.4 Routes of Administration of Nanoparticles
11.5 Conclusion
References
12 Promising Approaches in Drug Delivery Against Resistant Bacteria
12.1 Introduction
12.2 Drug Delivery Systems
12.3 Biofilm Disruption
12.4 Conclusion
References
13 Emulgels: A Novel Approach for Enhanced Topical Drug Delivery Systems
13.1 Introduction
13.2 Approaches Used for Topical Drug Delivery
13.3 Factors Affecting Topical Absorption of Drug
13.4 Drug Delivery Across the Skin
13.5 Emulgels
13.6 Conclusions
References
14 Electrospun Nanofibers in Drug Delivery
14.1 Introduction
14.2 Electrospinning Setup
14.3 Polymers Used to Produce Electrospun Nanofibers
14.4 Drug Release
14.5 Matrix Type NFs
14.6 Core-Shell Nanofibers
14.7 Electrospun Nanofiber for Drug Delivery Applications
14.8 Conclusion
References
Part II: DRUG CARRIERS IN DRUG DELIVERY
15 Role of Nanotechnology-Based Materials in Drug Delivery
15.1 Introduction
15.2 Nano-Based Drug Delivery Systems
15.3 Types of Nanoparticles
15.4 Advantages of Nanoparticles
15.5 Toxicity of Nanoparticles
15.6 Conclusion
References
16 Nanomedicine Drug Delivery System
16.1 Introduction
16.2 Background
16.3 Five Overlapping Subthemes of Nanomedicine
16.4 How Nanomedicine Work?
16.5 Nanomedicine for Screening of Individuals with Serious Diseases
16.6 Objectives of Nanomedicine
16.7 Advantages of Nanomedicine
16.8 Physiological Principles for Nanomedicines
16.9 Nanotoxicology from Nanomedicines
16.10 Nanomedicine Applications
16.11 Toxicological and Ethical Issues in Nanomedicine
16.12 Conclusions
References
17 Nanocarriers-Based Topical Formulations for Acne Treatment
17.1 Introduction
17.2 Acne Therapeutics
17.3 Efficacy and Safety of Nanotechnology-Based Acne Therapeutics
17.4 Improvement of Acne Therapy by Nanocarrier-Based Formulations
17.5 Conclusion
References
18 Emerging Trends of Ocular Drug Delivery
18.1 Introduction
18.2 Barriers to Ocular Drug Delivery
18.3 Classical Drug Delivery Technology
18.4 Novel Interventions for Ocular Drug Delivery
18.5 Applied Nanotechnology for Ocular Drug Delivery
18.6 Conclusion
References
19 Microspheres: An Overview on Recent Advances in Novel Drug Delivery System
19.1 Introduction
19.2 Advantages of Novel Drug Delivery System
19.3 Classification of Novel Drug Delivery System
References
20 Drug Delivery Systems and Oral Biofilm
20.1 Introduction
20.2 Oral Biofilm
20.3 Drug Delivery Systems
20.4 Applications of Drug Delivery Systems for Treatment of Oral Biofilm Infection
20.5 Conclusion
References
21 Oral Drug Delivery System: An Overview on Recent Advances in Novel Drug Delivery System
21.1 Introduction
21.2 Oral Drug Administration Sites
21.3 Factors Affecting Drug Absorption
21.4 Drug Delivery for Periodontitis
21.5 Oral Periodontitis Drug Delivery System
21.6 Teeth Treatments
21.7 Periodontal Local Drug Delivery
21.8 Carriers of Oral and Periodontitis Drug Delivery System
21.9 Mucoadhesive Drug Delivery System/Buccal Adhesive Drug Delivery System
References
22 Cancer Nanotheranostics: A Review
22.1 Introduction
22.2 Conclusion
References
23 Nanomedicine in Lung Cancer Therapy
23.1 Introduction
23.2 Nanotechnology
23.3 Nanomedicines for Lung Cancer Therapy
23.4 Evaluation of Nanoformulations
23.5 Application of Nanoformulations
23.6 Marketed Therapies
23.7 Challenges
23.8 Potential
23.9 Future Scope
23.10 Conclusion
References
24 Delivering Herbal Drugs Using Nanotechnology
24.1 Introduction
24.2 Methods of Preparation of Nanoparticles
24.3 Novel Drug Delivery Systems (NDDS) for Herbal Drugs
24.4 Conclusion
References
25 Nanoherbals Drug Delivery System for Treatment of Chronic Asthma
25.1 Introduction
25.2 Mechanism of Asthma Physiopathology
25.3 Asthma Etiology
25.4 Severity of Asthma
25.5 Asthma Phenotypes
25.6 Asthma Epidemiology
25.7 Asthma Treatment
25.8 Need of Natural Products as Alternative
25.9 Selected Medicinal Plants in Asthma Treatment
25.10 Potentials of Nanotechnology in Asthma Drug Delivery
25.11 Nanoherbals as Asthma Drug Delivery System
25.12 Future Prospectus of Nanoherbal Drug Delivery
25.13 Conclusion
References
26 Nutrients Delivery for Management and Prevention of Diseases
26.1 Introduction
26.2 Nutrients in Management and Prevention of Disease
26.3 Phenolic Nutraceuticals
26.4 Routes for Nutrients Delivery
26.5 Nanoparticle-Based Nutrients Delivery System
26.6 Protein-Based Nanoscale Delivery of Nutrients
26.7 Micelles
26.8 Advantages of Nanomaterials in Nutraceuticals
26.9 Safety and Toxicity of Nanostructures Applied in Food Systems
26.10 Conclusion
References
27 Nanonutraceuticals for Drug Delivery
27.1 Introduction
27.2 Approaches to Enhance Oral Bioavailability of Nutraceuticals
27.3 Carriers for Nutraceutical Delivery
27.4 Nanotechnology in Food Sector
27.5 Delivery of Nutraceuticals
27.6 Constraints in Nanodrug Delivery Systems
27.7 Conclusion
Acknowledgments
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Pros and cons of liposomes.
Table 1.2 Types of liposomes and their composition and applications.
Table 1.3 Application of dendrimers.
Chapter 3
Table 3.1 Various challenges of nanopharmaceuticals.
Chapter 5
Table 5.1 Effect of
Curcuma longa
nanocompounds.
Table 5.2 Effect of
Gingko biloba
nanocompounds.
Table 5.3 Effect of
Artemisia
nanocompounds.
Table 5.4 Effect of
Silybum marianum
nanocompounds.
Table 5.5 Biological effects of silymarin nanostructures.
Table 5.6 Summary of the effects of other plant nanoformulations.
Chapter 6
Table 6.1 Common nutraceuticals and their health benefits.
Table 6.2 Nanosystems for improved nutraceutical properties.
Table 6.3 Commercially available nanonutraceuticals.
Table 6.4 Clinical trials on nanonutraceuticals.
Chapter 7
Table 7.1 Frequently used techniques to nanoencapsulation plant compounds or e...
Table 7.2 Parameters detected by nanocapsule characterization techniques.
Table 7.3 Biological evaluation of nanoencapsulates loaded with phytopharmaceu...
Chapter 8
Table 8.1 Liposome formulations application in skin cancer.
Chapter 9
Table 9.1 Conventional dosage forms for the treatment of rheumatoid arthritis.
Table 9.2 Novel vesicular carriers for topical delivery.
Table 9.3 Marketed products based on vesicular carriers.
Chapter 13
Table 13.1 Use of various oils in emulgel formulations.
Table 13.2 Improved results of drug employed with different oil systems incorp...
Table 13.3 Various gelling agents used in emulgel formulation.
Table 13.4 Penetration enhancers used in emulgels with their quantity and dosa...
Table 13.5 Recent advancements of Emulgels with different categories of drugs ...
Table 13.6 List of marketed formulations.
Table 13.7 Drugs used in the preparation of nanoemulgel.
Chapter 15
Table 15.1 Therapeutic applications of polymeric nanoparticles.
Table 15.2 Therapeutic applications of dendrimers.
Table 15.3 Therapeutic applications of polymeric micelles.
Table 15.4 Therapeutic applications of liposomes.
Table 15.5 Therapeutic applications of nanocrystals.
Table 15.6 Therapeutic applications of gold nanoparticles.
Table 15.7 Therapeutic applications of carbon nanotubes.
Table 15.8 Therapeutic applications of magnetic nanoparticles.
Chapter 17
Table 17.1 Acne topical therapeutics based on nanotechnology.
Table 17.2 Safety and efficacy of anti-acne drugs entrapped loaded in nanocarr...
Table 17.3 Major contributions of anti-acne agents loaded in nanocarriers.
Chapter 18
Table 18.1 Some new interventions to increase efficacy of ocular drug delivery...
Table 18.2 Ocular barriers and effect on ocular drug delivery.
Table 18.3 Some important reports on nanosphere-based ocular drug delivery.
Chapter 20
Table 20.1 Main stages of oral biofilm formation.
Table 20.2 Oral bacteria microbiome.
Table 20.3 Oral bacteria related to oral diseases.
Table 20.4 Application of the DDS in oral infectious diseases.
Chapter 22
Table 22.1 Lipid and polymer-based cancer nanotheranostics.
Table 22.2 Magnetic cancer nanotheranostics.
Table 22.3 Quantum dot-based cancer nanotheranostics.
Table 22.4 Metal-derived cancer nanotheranostics.
Chapter 23
Table 23.1 Type of nanomedicines and their applications in chemotherapy.
Table 23.2 Commercial nanomedicines with indications.
Chapter 24
Table 24.1 Herbal formulations based on liposomal drug delivery system.
Table 24.2 Herbal formulations based on phytosomal drug delivery system.
Table 24.3 Herbal formulations based on transferosome drug delivery system.
Table 24.4 Herbal formulations based on niosome drug delivery system.
Table 24.5 Herbal formulations based on ethosomal drug delivery system.
Table 24.6 Herbal formulations based on dendrimer drug delivery system.
Table 24.7 Herbal formulations based on SNEDDS drug delivery system.
Table 24.8 Herbal formulations based on SMEDDS drug delivery system.
Chapter 25
Table 25.1 Available nanoherbals for asthma [89].
Chapter 26
Table 26.1 Few examples of encapsulated nutrients for treatment of diseases.
Chapter 27
Table 27.1 Delivery of nutraceuticals through various types of nanoparticles [...
List of Illustrations
Chapter 3
Figure 3.1 Different diagnostic applications of nanopharmaceuticals.
Chapter 6
Figure 6.1 Food source and nanosystems for nutraceuticals delivery. NE, nanoem...
Chapter 7
Figure 7.1 Nanoparticle type: noncapsular and nanospheres.
Chapter 8
Figure 8.1 Schematic illustration of liposome production by lipid phase inject...
Figure 8.2 Schematically depicted polymorphism of phospholipid aggregates.
Figure 8.3 Schematic representation of physical methods application in the ski...
Chapter 11
Figure 11.1 Advantages of nanoparticles.
Figure 11.2 Disadvantages of nanoparticles.
Figure 11.3 Nanoparticles used for antitubercular therapy.
Chapter 13
Figure 13.1 Various approaches for topical drug delivery.
Figure 13.2 Structure of emulgel.
Figure 13.3 Advantages of emulgel.
Figure 13.4 Preparation for emulgel.
Chapter 14
Figure 14.1 Overviews of the electrospinning process and its customised drug r...
Figure 14.2 Scanning electron microscope image of (a) poly-ε-caprolactone/gela...
Chapter 15
Figure 15.1 Types of nanomaterials used for drug delivery [16].
Figure 15.2 Structure of dendrimers [28].
Figure 15.3 Structure of polymeric micelles [47].
Figure 15.4 Types of liposomes [56].
Figure 15.5 Structure of quantum dots [65].
Figure 15.6 Structure of gold nanoparticles [86].
Figure 15.7 Advantages of nanoparticles [5, 87, 135, 136].
Chapter 16
Figure 16.1 Nanomedicine application areas.
Chapter 17
Figure 17.1 Pilosebaceous unit and acne etiology. Created in Biorender. PSU: p...
Chapter 18
Figure 18.1 Novel intervention of ocular drug delivery.
Chapter 20
Figure 20.1 Caries-preventive strategies that can reduce the risk of dental ca...
Chapter 23
Figure 23.1 Classification of nanotechnology.
Figure 23.2 Examples of nanocarrier system.
Figure 23.3 Nanoparticles.
Figure 23.4 Micelle.
Figure 23.5 Dendrimer.
Figure 23.6 Liposome.
Figure 23.7 (a) Single-walled carbon nanotube and (b) Multiwalled carbon nanot...
Figure 23.8 Quantum dot.
Chapter 24
Figure 24.1 Types of novel herbal drug delivery systems.
Chapter 25
Figure 25.1 Structure of nanoparticles.
Figure 25.2 Various nanomedicine approaches in lung diseases.
Figure 25.3 Mechanism of nanoherbal drug delivery for asthma treatment.
Chapter 26
Figure 26.1 Physiological factors affecting nutrients intake [21].
Figure 26.2 Physiochemical/nutraceutical factors affecting nutrients intake [2...
Chapter 27
Figure 27.1 Advantages of nanosizing.
Guide
Cover Page
Series Page
Title Page
Copyright Page
Preface
Table of Contents
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
Advances in Novel Formulations for Drug Delivery
Edited by
Raj K. Keservani
Faculty of B. Pharmacy, CSM Group of Institutions, Prayagraj, India
Rajesh Kumar Kesharwani
Department of Computer Application, Nehru Gram Bharati (Deemed to be University), Prayagraj, India
and
Anil K. Sharma
School of Medical and Allied Sciences, GD Goenka University, Gurugram, India
This edition first published 2023 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA© 2023 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-394-16643-5
Cover image: Pixabay.ComCover design by Russell Richardson
Preface
Drug delivery technology has witnessed a number of advancements purported to cater to the customized needs of its ultimate beneficiaries—the patients. Nowadays, dosage forms are not confined to conventional tablets, capsules or injectables, but have evolved to cover novel drug carriers such as particulates, vesicles and many others. Nanotechnological advancements have played a major role in this paradigm shift in ways of delivering active pharmaceutical ingredients; as researchers across the globe continue striving to provide site-specific (targeted) drug in the treatment of diseases.
A new dimension in the use of food as medicine has also gained prominence in recent years. A portmanteau of nutrition and pharmaceuticals is “nutraceuticals,” also known as functional foods and dietary supplements. The technologies which were earlier included in drug delivery parlance have been attempted for delivery of nutraceuticals as well. Herbal actives have received increased attention due to their low risk to benefit ratio.
The health of an individual should allow the performance of routine roles/responsibilities in a smooth manner. Any physiological disease/disorder may lead to impairment of the normal functioning of the human body. Since the beginning of human civilization, humans have acquired knowledge about medicines derived from mother nature, and researchers across the globe have served mankind by developing a number of natural and synthetic/ semi-synthetic medicines. Nowadays, food is also considered as a medicine, which has opened several avenues of possibilities in the domain of nutraceuticals, functional foods and dietary supplements. The field of drug delivery is quite dynamic in nature, as witnessed by its evolution from conventional dosage forms to nanotechnology-assisted drug products. A variety of formulations via different drug delivery routes have been developed with the objective to treat/cure/mitigate diseases or disorders.
This book is a compilation of information relevant to drug delivery systems with an emphasis on products based on nanotechnology. The contributors are from a diverse pool of academic and industrial researchers from different geographical locations across the globe. The 27 chapters described below compile novel strategies for drug delivery and embrace the development of formulations with herbal ingredients. Several chapters also highlight disease therapeutics.
Chapter 1
gives an overview of nanotechnology-based drug delivery systems. Several nanomaterials, such as liposomes, nanoparticles, aquasomes, nanogels, nanoemulsions, nanotubes, quantum dots, etc., are described that were found to have important roles in drug delivery to humans and animals. The general features, types and applications in drug delivery have been mentioned where applicable.
Chapter 2
discusses the incorporation of nanotechnology into the medical profession, which has resulted in the emergence of new multidisciplinary fields of nanomedicine such as nanopharmaceuticals. The formulation and evaluation of nanopharmaceuticals are addressed from a regulatory perspective for market authorization of the same.
Chapter 3
discusses current and future scenarios of nanopharmaceuticals. Potential challenges in commercialization of nanotechnology-based products are listed; and therapeutic applications of nanopharmaceuticals with site-specific drug delivery are also mentioned.
Chapter 4
offers a detailed description of the regulatory status of nanomedicines. It delineates the threats and opportunities for successful licensing in different markets. Newer approaches, such as personalized medicines, nano-robots and devices, lab-on-a-chip technologies and gene/protein delivery, are also mentioned in the latter half of the chapter.
Chapter 5
discusses several highly effective herbal pharmaceuticals produced at nanoscale level with improved bioavailability,
in-vitro
,
in-vivo
, and clinical efficacy. Phytoconstituents with pharmacological activity are also discussed in detail.
Chapter 6
describes the use of nanotechnology as a tool to deliver nutraceuticals. It also focuses on the drawbacks associated with nutraceuticals and presents different nanosystems (lipid, polymeric or inorganic) that have been used to improve their biopharmaceutical and health properties.
Chapter 7
offers relevant information on herbal actives confined in nanosystems. The types, preparation and applications for improved bioavailability and reduction in toxicity are discussed.
Chapter 8
entails topical drug delivery approaches for treatment of skin cancer. In particular, the chapter describes liposomes and liquid crystals as topical formulations which are derived using nanotechnology.
Chapter 9
presents an overview of vesicular carriers for control of arthritis. Vesicular systems are particularly significant for targeted delivery of drugs due to their ability to carry the drug to a particular site or organ of action, thus lowering its concentration in other sites of the body. Various pharmaceutical carriers, such as particulate systems, polymeric micelles, and macro- and micromolecules, are presented in the form of a novel drug delivery system.
Chapter 10
is about the use of novel drug delivery systems for fungal infestations. Nanotechnology in drug delivery has opened new paths in antifungal therapy, especially in the immunocompromised population, where drug toxicity has been a major concern.
Chapter 11
outlines various nanotechnology-based therapeutic approaches against tuberculosis (TB) and the challenges to their implementation. The chapter begins with an introduction to TB, its etiology and traditional therapeutic regimen. Subsequent text deliberates on nanotechnology in the treatment/control of TB.
Chapter 12
addresses the issue of drug-resistant bacterial infections via nanotechnological interventions. It includes recent advances in stimuli-responsive antibiotic-loaded nanoparticles which deliver targeted therapy by recognizing the presence of bacteria. Surface engineering the nanoparticles enables customizing the biological and physical properties of nanoparticles as well as attaching specific ligands.
Chapter 13
details the use of emulgels as a topical delivery system for treatment of different ailments. Emulgel is one of the innovative formulations commonly utilized for fungal infections, acne, psoriasis and other topical diseases. The chapter begins with an introduction to emulgels and then discusses the types, formulation aspects, evaluation and applications.
Chapter 14
is about a special nanotechnological advancement known as electrospun nanofibers. Electrospinning is a versatile technique for fabricating native tissue-like nanofibrous scaffolds. The chapter introduces this nanocarrier along with the types, polymers used for its formulation and therapeutic applications.
Chapter 15
contains basic information on nanotechnology, the need for emerging nanotechnologies, and the classifications of nanoparticles. The authors discuss different types of nanotechnology-based materials used in drug delivery, such as liposomes, dendrimers and micelles, and their properties and applications. The chapter also discusses the merits of nanoparticles over traditional drug carriers and the toxicity potential of these nanometric artefacts.
Chapter 16
describes nanomedicines and covers various aspects concerning their historical progress, rationale and mechanism of action, applications, toxicity and ethical concerns. It presents a concise audit of nanomedicines that accentuates different viewpoints related, for example, to presentation, foundation, objective, physiological standards of nanomedicine, etc. The chapter also delves into the concept of nanotoxicology from nanomedicines and non-clinical nanoparticles.
Chapter 17
entails the topical applications of nanocarriers in treatment of acne. The chapter begins with an introduction to acne therapeutics and then moves on to nanocarriers. Afterwards, a toxicity profile based on animal and clinicals studies as evaluation criteria is given. A vis-a-via comparison of conventional and nanocarrier-based dosage forms is presented in subsequent sections of the chapter.
Chapter 18
offers an overview of ocular drug delivery incorporating nanotechnology principles. The authors provide information on the anatomy of the eye with prevailing drug delivery systems. The successive text is relevant to applications of various nanotechnology-based drug carriers for treatment of ocular diseases.
Chapter 19
discusses microparticulate drug carriers in detail. Following their introduction to microspheres, the authors present an exhaustive overview of their advantages, types, evaluation characteristics and applications.
Chapter 20
focuses on drug carriers in oral biofilm infectious diseases. The authors discuss the role of biofilms in oral cavity infections. Furthermore, novel drug carriers are mentioned in relation to their utility in countering oral biofilm infections. The information provided will be helpful in identifying the most effective treatment using drug delivery systems, which has definitely become a trend in dentistry and the oral health sector.
Chapter 21
discusses oral drug delivery in a detailed fashion. The authors describe the inherent physicochemical properties of oral biomembranes and drug molecules, which are in fact vital variables in the success of any delivery system. Thereafter, the chapter discusses different drug delivery systems purported to address health concerns of the oral cavity. This is followed by specific information on muco/bioadhesive drug delivery systems.
Chapter 22
endeavours to inform the reader about recent advances in the field of cancer diagnostics and therapeutics. It reviews various polymeric/ non-polymeric theranostic nanosized systems and the opportunities they provide for the treatment of cancer.
Chapter 23
covers the applications and scope of nanomedicines in the treatment of pulmonary tumor (lung cancer). The nanotechnology-based interventions and applications used for cancer treatment are elaborated on. In addition, the existing marketed formulations are also mentioned.
Chapter 24
elaborates on nanotechnology-derived herbal formulations. It summarizes information on various novel techniques used for improving the safety and efficacy of phytomedicines, type of active ingredients, biological activity and application of novel formulation of herbal drugs to achieve a better therapeutic response.
Chapter 25
focuses on herbal nano-formulations meant for curing asthma. It discusses the current scenario in the treatment of asthma, the mechanism involved in asthma physiopathology and epidemiology, the use of herbal nano-formulations in asthma drug delivery system, their delivery route and efficiency. It is suggested that herbal-based nano-drug delivery is effective in the treatment of asthma with easier dissolution without any toxicity or incompatibility.
Chapter 26
highlights the role of nutrients in the prevention and treatment of diseases. The chapter describes beneficial plant constituents, such as poly-phenols, curcumin, proteins and carbohydrates, as medicines to combat diseases like cancer and nervous disorders. The nanometric carriers having these phytoconstituents are also described. In addition, regulatory perspectives on the clinical trials of herbals are also mentioned.
Chapter 27
reviews a variety of nutraceuticals for possible use in formulating nanocarriers. The chapter focuses on the benefits and new dimensions provided by nanomaterials and nanotechnology in the food and health sectors by improving treatment strategies and quality of life. In addition, a general introduction to nanocarriers for nutraceuticals is presented, which includes a list of approaches for bioavailability enhancement and barriers to the scale-up of nanomedicine as commercial products.
The Editors
December 2022
Part INOVEL DRUG CARRIERS AND THERAPEUTICS
1Nanoarchitectured Materials: Their Applications and Present Scenarios in Drug Delivery
Moreshwar P. Patil1 and Lalita S. Nemade1,2*
1Department of Pharmaceutics, MET institute of Pharmacy, Adgaon, University of Pune, Nashik, India
2Department of Pharmaceutics, Govindrao Nikam College of Pharmacy, University of Mumbai, Sawarde, India
Abstract
Nanotechnology is proposed to make a fundamental difference in drug production in the imminent years and will have a huge demeanor on life sciences, encircling drug delivery, diagnostics, nutraceuticals, and production of nanomaterials. The use of nanotechnology in medicine and, more specifically, drug delivery is bound to expand quickly. Engineered nanoparticles (NP) (<100 nm) are a key device to grasp a number of uses. For many years, pharmaceutical scientists have been employing nanoparticles to alleviate the toxicity and side effects of drugs. Exploration of such nanocarriers is active and yield more worthwhile therapeutic delivery via developments in material design, structural design, and cellular targeting. Several nanomaterials, such as liposomes, nanoparticles, aquasome, nanogels, nanoemulsion, nanotubes, quantum dots, and so on were found to have important roles in drug delivery to humans and animals.
Keywords: Nanotechnology, nanomaterials, therapeutic delivery, liposome, nanoemulsion
1.1 Introduction
Nanotechnology is one of the fastest developing areas of scientific research. Due to the advancement in nanotechnology, various nanomaterials exposed to humans in the form of different application. Technology progress has always had an impact on architecture means progress of science [1]. The revolution of nanotechnology is popular. Technology progress has always had an impact on architecture, means progress of science. The revolution of nanotechnology is popular concept in the scientific world. In addition, researchers have agreed this that it will offer great advances to design novel solution to treat the various diseases and health treating conditions in the modern Era.
Advance in the nanotechnology mainly directed by modifications in the observational methodology like advancement in the microscope. However the control of nanoscopic object is not easy on expected because the nanosize objects influences significantly on number of factors and also lead to thermal statistical fluctuations. They do not have independently and have substantial effect on one another. The interdisciplinary field of nanobiotechnology, which combines chemistry, biology engineering and medicine, is revolutionizing the development of drug delivery system.
Nanotechnology shown to bridge the barrier of biological and physical science by offering nanostructure and nanophase at different fields of science. Nanomaterial can well defined as material with size range between 1 and 100 nm, which impacts frontier of nanomedicine. Nanotechnology employs curative agents at the nanoscale level to develop nanomedicine. Nanomedicine is an emerging trend of implementing the use of knowledge and techniques of nanoscience in medical biology and disease prevention and remediation. Nanoscale drug delivery materials 10-9 to 10-7 can exhibit distinctive physical, electrical mechanical, and optical properties that differ from those observed in macroscopic and atomic realm [133]. And widely used in pharmaceutical for the sensitive detection of key biological molecules more precise and safer imaging of diseased tissue and novel form of therapeutics because nanoscale material developed with more efficient and less toxic, due to their less toxicity and high efficiency with enhanced distribution [43]. Nanoparticle can alienate into following main areas that is engineered nanoparticles and nonintentionally produced nanoparticles. The examples of nanoparticles are nanoemulsion, nanocapsules, liposome, nanoparticles, nanosomes, quantum dots, dendrimer, fullerene fluorescent dextran beads, soil particles (0.4–0.5 micron), and biopolymers. At present, people have started to play attention to nanomaterial development. Now the application of nanoarchitectured materials in medicine and pharmaceuticals have become a large subject area including nanomaterial that acts as biological memetics, nanomachines, nanofibered and polymeric nanostructured as biomaterial [133, 134]. In contemporary decades, biodegradable polymeric nanoparticles especially those developed with hydrophilic polymer like polyethyleneglycol (PEG), also named as circulating particle have been employed as potential drug delivery. Due to their capability to travel for longer span to target a specific organ, as carrier if DNS in gene therapy ND their capacity to carry proteins, peptides, and genes.
1.2 Liposomes
Liposomes are a liquid crystalline mesophase (lyotropic) liquid crystals involved relatively biocompatible and biodegradable constituents and contain an aqueous core confined in one or more bilayers of lipids of natural and/or synthetic origin. Liposomes offer an exceedingly flexible scaffold. Liposomes are designed in varieties from multilamellar vesicles (MLVs) having extent of many microns to tiny, unilamellar vesicles of sizes ranging 20 nm. Liposomes are promising systems for drug due to their size and hydrophobic and hydrophilic character (besides biocompatibility). The vesicle size is a key variant in assessing the circulatory half-lives of liposomes, and equally size, as well as number of bilayers influences the extent of drug entrapment within liposomes. Based on dimensions and number of bilayers, liposomes may categorized in two classes: (1) multilamellar vesicles (MLV) and (2) unilamellar vesicles. Unilamellar vesicles may further be differentiated into (1) large unilamellar vesicles (LUVs) and (2) small unilamellar vesicles (SUV). The merits and pitfalls of liposome drug carriers completely based on colloidal and physicochemical attributes like their natural signaling from end to end the cell casings and size, makeup, incorporation efficiency and stability. There are four main activities between liposomes and cells properties of liposomes.
Liposomes can entrap both hydrophobic and hydrophilic compounds, avoid rottenness of the trapped combinations, and release the trapped at labeled targets. The characteristics of liposomes vary noticeably by lipid makeup, surface charge, size, and the technique of formulation, and these described in Table 1.1 [1].
Major complications in getting treatment using conventional chemotherapeutics are general bioavailability and noxiousness at the site of tumor (Loose drug is lethal to usual cells and attains peak plasma contents in 5 min resulting in bolus injection) [2]. To improve the biodistribution of such pharmaceuticals, reduce free toxicity of drug moiety, and promote accumulation of tumor on specific site [3, 4], investigations of drug delivery, preclinical testing techniques, method of clinical assessment, and marketable scale up have chiefly focused on liposome mainly containing phospholipid [5, 6]. Some nanoparticles and liposomes also might attain tumor-targeted perivascular build up modestly via passive extravasation concluded from the in vivo experiments [7–9].
In 1978, the first thermoresponsive liposome was made [10]. The efficiency of temperature-sensitive liposome was investigated by preclinical study and has verified its greater antitumor characteristics, as a consequence of its capability to deliver drug to the tumor at amounts up to 30-fold more than those feasible with free drug, and 3 to 5 higher than those of traditional liposomes [11, 12]. Kono et al., too, utilized polymers and assigned thermoresponsive liposomes made up of dioleoylphosphatidyl ethanolamine altered using copolymers of N-acryloylpyrrolidine and N-isopropylacrylamide to consign thermoresponsive liposome. These copolymer-altered liposomes were impregnated with calcein to study the release mechanism and bench top stability. The investigators revealed that the addition of the anchor-possessing PEG derivative in the thermoresponsive liposomes boosts the kinetics of drug release and temperature sensitivity [13]. Liposomes having dissimilar makeup may roughly attach to the surface of cell. In order to gene transfer, it was recognized that dioleylphosphatidyl ethanolamine (DOPE) is definitely the most proficient lipid for in vitro gene transfection for pH-sensitive liposomes or as a lipid supporter in cationic liposomes [14]. Brain tumors like glioblastomas, which are too aggressive, and using an appropriate warming device can avail breakdown of such tumor after hyperthermia handling procedure. In comparison, patient suffering from glioblastoma tumor is treated by brachytherapy, as well as radiotherapy. In randomized hyperthermia phase III trial in the presence or absence of hyperthermia procedure. To cure breast cancer, hyperthermia can also be a vital adjuvant. A modern meta-analysis approved by premature stage of breast cancer trialist group. Liposomes are a beneficial approach for pulmonary drug delivery because of poor solubilization capacity for less soluble drug permitting them more applicable for aerosolization. In ophthalmic drug delivery, by applying liposomal, vehicle delivery of drug may be recovered or diminished, which is based on the physicochemical characteristics of drug and lipid mixture used. More tissue safety and higher the activity of enzyme following safely to pulmonary application of liposome which contain catalase and superoxide dismutase [15].
Table 1.1 Pros and cons of liposomes.
Advantages
Disadvantages
Liposome increases the efficiency and therapeutic index of drug like actinomycin D
Not as much of solubility
1. Liposome significantly improved the stability through encapsulation process
Less half life
2. Liposomes are completely nontoxic, biocompatible, wholly biodegradable and nonimmunogenic of systemic and nonsystemic uses for their administration
Intermittently, phospholipid may endure degradation like oxidation and hydrolysis reactions
3. Ability to bypass the specific site
Unacceptable stability
4. Liposome minimizes the toxicity of encapsulated drug moiety like Taxol and amphotericin B
Sometimes drug moiety may fuse or leak from encapsulated material
5. Liposomes are helpful for the reduction of sensitive tissues to toxic drugs
Product price increases
6. To achieve active targeting liposome have flexible to connect with site specific
In comparison to free rifabutin with liposomal rifabutin, which gives the excellent improvement of activity alongside mycobacterium avium infection [16], also within corporation of rifampin in egg phosphotidyl choline liposome, the antitubercular effect substantially augmented. Liposome generally prepared with polymer, phosphotidyl choline shows the promptness of preparation, better compatibility wide range of compatibilities of drug modification in their solubility behavior of drug like cyclosporine A [17] smooth pharmacokinetic profile with greater oral absorption. Generally, they pose complications on oral delivery because of the unacceptable stability of the vesicles beneath the physiological location generally present in the GI tract. A variety of some antineoplastic liposomal preparation was found to be less toxic than the plain drug. Therefore, most of the liposomes that have shipped to the preclinical phase are in cancer cure [17–19].
Liposomal preparation archaeosomes are produced by using one or more lipids, mainly having ether bond that maybe (diether and/or tetraether) present in archaeobacterial membrane [20]. The archaeobacterial lipids offer excellent properties and more stabilities to different milieus (highest or lowest temperatures, aerobic atmosphere, acidic media, higher salinity) over traditional [21]. Though liposomes can be like biomembranes, till now they are considered as xenobiotic for the body. Hence, liposomes are known by the mononuclear phagocytic system (MPS) successive to coming in area of plasma proteins. Ultimately, liposomes are eliminated from the blood stream. Since from last two eras, several polyethylene glycol derivatives have been utilized to make the liposome more compatible to improve the competence in delivery of drug or gene. Major stabilized liposomes, also known as stealth liposomes or cryptosomes [22, 23], possess a precise amount of PEG-derivatized phospholipids, which improves the uptake by MPS, thus by extending the residence time and offering amply of period for such liposomes to trickle from the circulation across the leaky endothelium.
Liposomal preparation may be useful for the delivery of drug for their topical and oral drug targeting. They achieve through the mechanisms as follows [24]. To release the contents from liposome into the cell, they should attach to the cellular membranes and act to be fused by them. Occasionally, liposomes are occupied up by the cell and their phospholipids are fused into the cell membrane by which the drug is entrapped inside the liposome and released. In the case of phagocytic cell, liposomes are occupied, and the phospholipid walls are replaced by organelles this process named as lysosomes and trapped drug is released from the formulation.
Various types of liposomal preparation, with their composition and applications, are illustrated in Table 1.2.
In liposome, the number of ingredients is extant, but key component is cholesterol and phospholipid [25]. Frequently, phosphatidyl choline phospholipid is employed. Several other phospholipids, like phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl glycerol and phosphatidyl inositol may also be used for liposomal preparation. For the diverse application, cholesterol is mixed with a bilayer mixture [24, 25].
In poorly aqueous soluble drug, exclusively for parenteral delivery of drug, lipid-centered drug-delivery system preferred, which is named as emulsome [26]. Emulsomes hold the characteristics of emulsion, as well as liposomes. In emulsomes, the internal core is encompassed of triglycerides and fats, by accumulation of excessive comfortable amount of lecithin emulsomes are stabilized in form of o/w emulsion.
Table 1.2 Types of liposomes and their composition and applications.
Type of liposome
Composition
Applications
Convectional liposome
Negatively charged or neutral phospholipids with cholesterol
Antimicrobial agent for their targeted delivery towards macrophages, vaccination
Cationic liposomes
Positively charged cationic lipids
Delivery of gene
Magnetic liposomes
Lesser amount of linear chain aldehyde and colloidal particles of magnetic iron oxide, cholesterol, phosphatidyl choline
Explicit targeting of antibodies to brain
pH-sensitive liposomes
Phospholipid-like phosphatidyl ethanolamine dioleoyl phosphatidyl ethanolamine
Tumor targeting, coated pit endocytosis
Long circulatory liposome
Neutral high transition temperature, lipid, cholesterol and 5–10% of polyethylene glycol
Careful flattening to pathological areas
Immunoliposomes
Long circulatory or conventional liposomes with attached anti-body or recognition sequence
Subject to receptor-mediated endocytosis, specific targeting
Liposomes linked with an antibody precise for the tumor antigen called as immunoliposomes. The antibody maybe close to the surface of a stealth liposome, the polyoxy ethylene covering of a stealth liposome or on the surface of a nonstealth liposome. These immunoliposomes, when injected into body, travels to the target site upon injection inside the body and make a depot in their location of action. This relieves undesired effects and enriches the drug delivery to the target tissue, in this manner its safety and efficacy was improving [27]. A several number of liposomal preparations of in numerable anticancer agents were found to have less toxicity than the free drug [28–31]. The substances inhibit the growth of repeating cells by engaging into the DNA called anthracyclines, thus, mainly destroying proliferating cells. Such cells are present in blood cells, also tumors, gastrointestinal mucosa, and hair; hence, this drug is in the highly toxic category. Commonly utilized and explored drug is doxirubicin hydrochloride. Mentioned acute toxicity and its dose are limited by its improving cardiotoxicity.
1.3 Nanoparticles
The major problem is delivery of drug or therapeutic compound to the specific target. So, for the last few eons, there has been generous research attention to the region of drug delivery by means of particulate delivery systems as carriers for small and large molecules. Delivery of the drug may be completed by the best of the traditional modes, such as oral administration, injections, and intravenous or per rectum. The only limitation of nanoparticles is the time period required and reactivity of drug. Particulate systems, like nanoparticles, have been used as a physical approach to improve and change the pharmacodynamics and pharmacokinetic properties of several drug molecules. In regular practice of nanomaterials, they improved the circulation and preserved the essential reactivity of the drug; it even abbreviated the timespan essential for the treatment. Nanoparticles are colloidal particles that range in size from 10 to 1000 nm in diameter, and developed by employing biodegradable polymers in which a therapeutic agent can be chemically coupled, encapsulated, adsorbed. They have been used in vivo for protection of the drug entity in the systemic circulation, restrain contact of the drug to the selected sites, and to deliver the drug at sustained and regulated rate to the site of action. Several polymers have been demoralized in the basis of nanoparticles for the delivery of drug to enlarge therapeutic value of drug through weakened side effects. A conventional application of drugs is characterized by and lack of selectivity, limited effectiveness, poor biodistribution [32], while nanoparticles can be used in targeted drug delivery at the site of disease to improve the uptake of poorly soluble drugs, the targeting of drugs to a specific site, drug bioavailability, biodistribution, and functionality. The source material for nanoparticles can be of the biological origin like lipids, dextran, phospholipids, chitosan, lactic acid or several polymers like carbon silica and metals. For the delivery of various drugs, such as nanoparticles, are adapted as nanocarrier. Further, to avoid the toxic side effects, it should be readily eliminated from body, and for this, the drug needs to be nonimmunogenic and nontoxic, which is used for nanoparticle preparation [32].
1.3.1 Nanoparticles in Drug Delivery
To compare the safety and efficacy of deoxycholate and liposomal formulation of amphoteresin zB (lipid) in neonates for the treatment of invasive fungal disease (IFD) [33]. DNA vaccination using PEI/γ PGA NPs loaded with a plasmid encrypting P. yoeliimerozoite surface protein 1 C terminus, administered through IV route in mice, has been revealed to seed an antigen-specific IgG response conquered by IgG1 and IgG2 band to motivate weak Th1 (IFN-γ and IL-12 p40) and robust Th2 (IL-4) cytokine responses [34].
Nanosomes also termed as probes encapsulated by biologically localized embedding (PEBBLEs) which embrace number of facets of medical uses like diagnosis, therapy, and targeting. This work has been carried out in the University of Michigan, USA by Raoul Kopelman’s group. For the treatment of several tumors especially CNS tumors nanosomes are being formulated. Using polyethylene glycol stucked with contrast element (gadolinium) and targeting antibody, they are abused to get the definite regions of brain inherent with the help of silica-coated iron oxide nanoparticles [35].
For the central nervous system, the most important factor limiting the development of new drugs is blood-brain barrier (BBB). The BBB is characterized by relatively impermeable endothelial cells with enzymatic activity, active efflux transport systems and tight junctions. It has been reported that poly (butyl cyanoacrylate) nanoparticles were able to deliver hexapeptide dalargin, doxorubicin, and other agents into the brain, which is significant because of the great difficulty for drugs to cross the BBB [36]. Many active targeting campaigns were related to the enhanced permeability and retention (EPR) effect, so mechanisms like passive and active targeting turn synergistically and result in a greater amount of nanostructures in the infected area than that in healthy tissues [37]. Targeted antimicrobial drug delivery to the site of infection, in particular intracellular infections, engaging with nanoparticles is an amazing prevision in treating contagious complaints [38, 39].
The magnetic nanoparticiles of vanncomycin investigated the magnetic nanoparticles of vancomycin for the detection of pathogen. Nanomaterial scan enter the human body through several ports, after oral uptake in the digestive system and after inhalation is the lungs. They can cross the blood test is barrier, as well as blood-brain barrier [40, 41]. Nowadays, several nanoparticles have been discovered to strive for several possibilities for drug delivery. Magnetic nanoparticles, in particular iron oxide (also called magnetite or Fe3O4) nanoparticles (MNPs) and their multifunctionalized foils are an important class of nanoscale materials that have attracted great interest for their potential applications in drug delivery and disease diagnosis. These types of nanoparticles (MNPs) have been emphasis on huge interest due to their potential applications in nanomedicine [42]. This includes the magnetic bioseparation, drug delivery, targeted therapy imaging, and biological detection.
Gold nanoparticles (AuNPs) have appeared as noticeable drug delivery vehicles. Few of the characteristics of AuNPs make it valuable for the application in drug delivery. AuNPs have a stable atomic core, great surface activity, nontoxic, electrical and thermal conductivity, strength, and elasticity. These have been synthesized with plentiful biomolecular coatings, which keep biological uses. The drug to be delivered is conjugated with AuNPs with ionic, covalent bond, or physical adsorption. The surface of the nanoparticle may be altered with many conjugates. For the treatment of cancer gold nanoparticles are hired. AuNPs have exceptional electrical and optical features; they are biocompatible and with little toxicity. They are also utilized as CT contrast agents, biosensors, and optical imaging agents [43].
1.4 Nanoemulsions
Nanoemulsion is a heterogeneous system and it comprises of two immiscible phases, one phase is oil phase other is aqueous phase, although the droplet is of submicron size range of 5 to 200 nm. It is thermodynamically stable, optically clear and transparent [44]. The inherently high colloid stability of nanoemulsions can be well understood from a consideration of their stearic stabilization when using nonionic surfactants and/or polymers) and how this is affected by the ratio of the adsorbed layer thickness to droplet radius [45]. Improvement in the solubility of drug is one of the most imperative tasks in the pitch of pharmaceutics. Approximately 40% of all new pharmacologically active molecules exhibits poor aqueous solubility, results in their less effective content in biofluids and hence, low bioavailability. It can be used through different ways such as oral route, pulmonary route. Nanoemulsions are habitually used comprising different surfactants in delivery of vaccine, DNA-encoded drugs, development of antibiotics, cosmetic, and topical dosage forms [44].
1.4.1 Advantages and Shortcomings of Nanoemulsions
The advantages and disadvantages of nanoemulsions are enlisted here [46, 47].
Advantages:
It is nontoxic as well as nonirritant.
It also deals with the taste concealment.
Nanoemulsions can deliver hydrophilic as well as lipophilic drugs moiety.
Nanoemulsions are kinetically and thermodynamically stable hence, aggregation, creaming, cracking, coalescence and flocculation do not take place.
Oral, parenteral, topical, transdermal and soon are the routes of administration of nanoemulsion.
Due to their nanodroplet surface area increases and rate of absorption and variability diminishes that significantly improved the rate and extent of the drug.
Nanoemulsions are apposite for both human as well as veterinary application.
It shelters the drug from degradation like hydrolysis and oxidation because of incorporation in oil-droplet.
Increases permeation of a drug via skin through nanoemulsion.
Shortcomings:
Use of huge amount of surfactants/cosurfactants is required for stabilization of nanoemulsion.
Its stability of nanoemulsion is distressed by pH and temperature.
In stability maybe because of the Oswald ripening effect.
1.4.2 Application of Nanoemulsion in Drug Delivery
Intranasal drug delivery system has now been considered as a trustworthy route of administration for the use of drugs after administration through parenteral and oral routes. Nasal mucosa is a therapeutically feasible channel for the administration of systemic drugs and also looks to be a beneficial approach to avoid the hurdles for the direct access of drugs to the specific target site [48]. Nanoemulsion formulation containing risperidone as drug for delivery of the drug to the brain through nose has been documented. It was concluded that this emulsion has much efficiency via the nasal rather than intravenous route. Drug delivery across the skin to the systemic circulation is comfortable for a number of clinical situations, which is why there has been extensive curiosity in this field [48, 49]. It delivers the excellence of steady state, controlled drug delivery over prolonged periods of time, as well as self-administration, which may not be achievable with the parenteral route of administration. Although oral delivery for diverse cancers caffeine has been utilized as a curative agent, for transdermal drug delivery, W/O caffeine have been designed. Appraisal of in vitro skin permeation profile between these and aqueous caffeine solutions showed crucial growth in permeability for the drugs loaded in nanoemulsion [50]. Gaur and others prepared formulation of bifonazole as nanoemulsion gel and concluded that nanoemulsion served as a better contraption to traverse the drug through the skin layer due to its very small size. When hydrophobic drug incorporates as gel formulation and gel provides a sustained effect to overcome the shorter half-life of the drug [51].
Nanoemulsions containing thalidomide have been prepared with a minimum dose of 25 mg results in plasma concentrations, which may be helpful as therapeutics [52]. However, a noteworthy reduction in the drug concentration in the nanoemulsion was seen in a case of 0.01% drug preparation after placing for 2 months which might be prevented by using polysorbate [80]. Chlorambucil, alipophilic anticancer agent, has been employed against breast and ovarian cancer. Carbamazepine, a commonly superfluous anticonvulsant drug without parenteral treatment for patients because of its less water solubility. Kelmann et al. (2007) have formulated a nanoemulsion for its intravenous delivery, which demonstrates promise for in vitro release kinetics. For the targeting and control drug delivery, the process of practice of nanoemulsion is an active development [53]. Nanoemulsions are oppressed as ocular drug delivery systems so as to offer a depot for the sustained release of drugs.
1.5 Dendrimers
Highly branched, synthetic monosuspended spherical macromolecules having nanosize are dendrimer, formulated by repeating synthetic procedures. Since the innovative research of Tomalia and Newkome [54, 55] on dendrimer creation in the initial 1980s, several research assemblages have backed synthetic performances and specific uses for this area.
Dendrimers with highly regular branching pattern infuses these dendritic architectures with well-defined numbers of periphery functional groups, with good opportunities of drug molecule for targeting moieties, and solubilizing groups on the surface in a multivalent fashion. Similarly, due to hydrophilic and hydrophobic cavities in inside the dendrimers make them expedient candidates as unimolecular micelles for the encapsulation of drug molecule inside the cavity of dendrimer [56]. In dendrimers, channeled drug delivery polymeric micelles offer a model. In polymeric micelles, the drug molecules may be confined within the inner hydrophobic and outer hydrophilic with improved aqueous solubility. However, the polymeric aggregates isolate into free chains, triggering the burst release of the drug under/at the critical micelle concentration. Newkome et al. have synthesized a dendritic unimolecular micelle having hydrophobic interior and hydrophilic surface functionality to bypass this trouble. Different from polymeric micelles, these unimolecular micelles do not separate because they are covalently linked. The internal hydrophobic cavities of such unimolecular micelles were found to solubilize several hydrophobic guest molecules [57]. Probably, the polyamidoamine (PAMAM) dendrimer is highly explored in delivery of drug. In another way, synthesis of PAMAM dendrimers originates from Michael addition reaction, which is amine functional core reacts with methylacrylate. This yields the synthesis of two new branches of peramine group with ester terminated dendrimer, which is known as a “half-generation” dendrimer. Further amidation of the methyl ester with ethylene diamine fallouts in a“full-generation”amine-terminated dendrimer. Reoccurrences of amidation and Michael addition and steps yields the next-higher “generation” dendrimer with additions to its size, molecular weight, number of terminal functional groups [58].
1.5.1 Synthesis of Dendrimers
Dendrimers may be created by two main methods. In the divergent method, the synthesis instigates from the core of the dendrimers to which the arms are attached by adding building blocks in an extensive and stepwise manner. This process enables dendrimers with incrementally cumulative generation numbers. Even so, only one type of reaction can be accomplished at each step, yielding an even exhibition of only one functional group on the exterior surface of dendrimer; besides, imperfections in consecutive groups may appear because of partial reactions or steric interference. Dendrons or small branches are synthesized beginning from the building blocks having surface groups; these relationships reduce afterward with a multivalent core.
1.5.2 Advantages of Dendrimers
Dendrimers have the following advantages:
