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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Serie: Adhesion and Adhesives - Fundamental and Applied Aspects
- Sprache: Englisch
This important and unique book comprises 12 chapters divided into three parts examining the fundamental aspects, bioadhesive formulations, and drug delivery applications. Understanding the phenomenon of bioadhesion i.e. its theories or mechanism(s) are of critical importance in developing optimum bioadhesive polymers (used in bioadhesives). Such bioadhesive polymers are the key for exhibiting the process of bioadhesion, controlled/sustained release of drugs, and drug targeting. The use of bioadhesives restricts the delivery system to the site of interest and thus offers a useful and efficient technique for targeting a drug to the desired location for a prolonged duration. This book addresses the various relevant aspects of bioadhesives in drug delivery in an easily accessible and unified manner. The book containing 12 chapters written by eminent researchers from many parts of the globe is divided into three parts: Part 1: Fundamental Aspects; Part 2: Bioadhesive Formulations; Part 3: Drug Delivery Applications. The topics covered include: Theories and mechanisms of bioadhesion; bioadhesive polymers for drug delivery applications; methods for characterization of bioadhesiveness of drug delivery systems; bioadhesive films and drug delivery applications; bioadhesive nanoparticles; bioadhesive hydrogels and applications; ocular biodhesive drug delivery systems; buccal bioadhesive drug delivery systems; gastrointestinal bioadhesive drug delivery systems; nasal bioadhesive drug delivery systems; vaginal drug delivery systems; pulmonary bioadhesive drug delivery systems.
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Veröffentlichungsjahr: 2020
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Table of Contents
Cover
Preface
Part 1: FUNDAMENTAL ASPECTS
1 Introduction, Theories and Mechanisms of Bioadhesion
1.1 Introduction
1.2 Bioadhesive Interactions
1.3 The Mechanistic Approach to Bioadhesion
1.4 Factors Controlling Bioadhesion
1.5 Theories of Bioadhesion
1.6 Stages of Mucoadhesion
1.7 Modulation of Mucoadhesion
1.8 Adhesion Promoters
1.9 Surface Free Energy Analysis of Bioadhesion
1.10 Molecular Biology in Bioadhesion
1.11 Bioadhesives from Marine Sources
1.12 Mucoadhesive Drug Delivery Systems
1.13 Summary
References
2 Bioadhesive Polymers for Drug Delivery Applications
2.1 Introduction
2.2 Bioadhesive/Mucoadhesive Drug Delivery Systems
2.3 Mechanism of Bioadhesion
2.4 Requirements for an Ideal Bioadhesive/ Mucoadhesive Polymer
2.5 Factors Affecting Bioadhesion/Mucoadhesion
2.6 Bioadhesive Polymers for Drug Delivery Applications
2.7 Prospects of Bioadhesive/Mucoadhesive Polymers in Bioadhesive Drug Delivery
2.8 Summary
Acknowledgements
References
3
In Vitro, Ex Vivo
and
In Vivo
Methods for Characterization of Bioadhesiveness of Drug Delivery Systems
3.1 Introduction
3.2 Mechanisms of Bioadhesion
3.3 Bioadhesive Drug Delivery Systems (BDDS)
3.4 Methods for Testing Bioadhesive Property of BDDS
3.5 Summary
References
Part 2: BIOADHESIVE FORMULATIONS
4 Bioadhesive Films for Drug Delivery Systems
4.1 Introduction
4.2 Theories of Bioadhesion
4.3 Bioadhesive Film-Forming Agents
4.4 Drug Delivery Applications of Bioadhesive Films
4.5 Current and Novel Bioadhesive Film Fabrication Techniques
4.6 Evaluation of Bioadhesive Films
4.7 Summary
4.8 Acknowledgements
References
5 Redox-Responsive Disulphide Bioadhesive Polymeric Nanoparticles for Colon-Targeted Drug Delivery
5.1 Introduction
5.2 Mechanism of Disulphide Bond Formation
5.3 Disulphide Polymers for Colon Drug Delivery
5.4 Colon-Targeted Drug Delivery (CTDD)
5.5 Nanoformulations of Disulphide Polymers
5.6 Summary
Acknowledgements
References
6 Bioadhesive Hydrogels and Their Applications
6.1 Introduction
6.2 Bioadhesive Hydrogel Films
6.3 Bioadhesive Hydrogels for Gastrointestinal Delivery
6.4 Bioadhesive Hydrogels Administered through Injection
6.5 Bioadhesive Hydrogels for Vaginal Delivery
6.6 Bioadhesive Hydrogels for Rectal Delivery
6.7 Mucoadhesive Hydrogels Based Nanoparticles
6.8 Patents and Future Perspectives
6.9 Summary
References
Part 3: DRUG DELIVERY APPLICATIONS
7 Ocular Bioadhesive Drug Delivery Systems and Their Applications
7.1 Introduction
7.2 Anatomy and Physiology of the Eye
7.3 Various Bioadhesive/Mucoadhesive Polymers for Ocular Delivery
7.4 Summary
References
8 Buccal Bioadhesive Drug Delivery Systems and Their Applications
8.1 Introduction
8.2 Theories of Bioadhesion
8.3 Factors Affecting Bioadhesion
8.4 Mechanism of Buccal Absorption
8.5 Buccal Bioadhesive Drug Delivery Systems
8.6 Quality Control Tests of Buccal Bioadhesive Dosage Forms
8.7 Marketed Formulations
8.8 Summary
References
9 Gastrointestinal Bioadhesive Drug Delivery Systems and Their Applications
Abbreviations
9.1 Introduction
9.2 The Mucus Layer
9.3 Gastrointestinal Bioadhesive Drug Delivery Systems
9.4 Summary
References
10 Nasal Bioadhesive Drug Delivery Systems and Their Applications
10.1 Introduction
10.2 Challenges in Nasal Drug Delivery Formulations
10.3 Mucoadhesion
10.4 Summary
References
11 Vaginal Bioadhesive Drug Delivery Systems and Their Applications
11.1 Introduction
11.2 Vaginal Anatomy and Physiology
11.3 Vaginal Absorption of Drug
11.4 Conventional Drug Delivery Systems for Vaginal Application
11.5 Mucoadhesive Drug Delivery Systems
11.6 Recent Advancements in Vaginal Drug Delivery Applications
11.7 Summary
References
12 Pulmonary Bioadhesive Drug Delivery Systems and Their Applications
12.1 Introduction to Pulmonary Drug Delivery Systems
12.2 Bioadhesives in Pulmonary Drug Delivery Systems
12.3 Development of Pulmonary Bioadhesive Drug Delivery Systems
12.4 Progress and Clinical Challenges for Bioadhesive Drug Delivery with Future Prospects
12.5 Future Prospects and Summary
References
Index
Also of Interest
End User License Agreement
List of Tables
Chapter 3
Table 3.1 Proposed theoretical considerations in mechanisms of mucoadhesion [...
Table 3.2 The main factors affecting bioadhesive interactions between BDDS an...
Chapter 4
Table 4.1 Chemical names and applications of some bioadhesive film-forming ag...
Table 4.2 Comparison of film preparation using casting and extrusion techniqu...
Chapter 6
Table 6.1 Different mucoadhesive polymeric systems and their application.
Table 6.2 Main types of hydrogel-based products applied via different routes ...
Table 6.3 Self-healing, pH-sensitive and temperature-sensitive mussel inspire...
Table 6.4 Patents filed by different inventors on bioadhesive hydrogels.
Chapter 8
Table 8.1 Drugs, mucoadhesive polymers and dosage forms.
Table 8.2 Commercially available buccal bioadhesive products.
Chapter 10
Table 10.1 Marketed nasal drug formulations.
Table 10.2 Factors affecting mucoadhesive interactions.
Table 10.3 Theories proposed for mucoadhesive interactions.
Table 10.4 Summary of different mucoadhesive materials used in formulation of...
Chapter 11
Table 11.1
In situ
gelling formulations for vaginal applications.
Table 11.2 Polymer nanoparticles for vaginal drug delivery.
Chapter 12
Table 12.1 Nanoparticles in respiratory applications [39].
List of Illustrations
Chapter 1
Figure 1.1 Various factors affecting mucoadhesion.
Figure 1.2 Interaction between water molecules and mussel adhesive protein....
Figure 1.3 Spreading of bioadhesive liquid over a typical soft tissue surfac...
Figure 1.4 Interactions resulting from inter-diffusion of polymer chains of ...
Figure 1.5 Regions that represent rupture of the mucoadhesive bond.
Chapter 3
Figure 3.1 Modified balance used to measure mucoadhesive strength
Figure 3.2 Modified two-arm balance to measure the tensile strength
Figure 3.3 Schematic diagram illustrating bioadhesion measurement by the mod...
Figure 3.4 Schematic representation of bioadhesion testing by measuring the ...
Figure 3.5 Schematic illustration of
in vitro
testing of bioadhesion
Figure 3.6 Experimental set-up to study the intestinal transit of microspher...
Chapter 4
Figure 4.1 Contact angle between a pharmaceutical dosage form and mucous mem...
Figure 4.2 Mucoadhesion by inter-diffusion of the bioadhesive polymer film a...
Figure 4.3 Topical medicated adhesive patch/film in different models
Figure 4.4 Working mechanism of a film-forming system.
Figure 4.5 Bioadhesive film strength test assembly.
Figure 4.6 Schematic representation of a vertical Franz diffusion cell.
Chapter 5
Scheme 5.1 Oxidative mechanism by DMSO. The rate of reaction is dependent on...
Figure 5.1 Anatomy of the human GIT.
Figure 5.2 Structures of (a) thiolated pectin, (b) pectin–cysteine conjugate...
Figure 5.3 Chemical structures of SA thiomers (a) alginate-4-ATP, (b) algina...
Figure 5.4 Structure of pCA–HT–chitosan conjugate.
Figure 5.5 Reaction mechanism of thiolated HA by amide bond formation and co...
Figure 5.6 Synthesis of (a) thiourea–PVA conjugate, (b) 3-mercaptopropionic–...
Chapter 6
Figure 6.1 Different classification criteria for categorization of hydrogels...
Figure 6.2 The precursor components of the adhesive, PDA and PEI, define the...
Figure 6.3 Schematic of injectable citrate-based mussel-inspired bioadhesive...
Chapter 7
Figure 7.1 Randomly tangled polymer network for long lasting mucoadhesion.
Figure 7.2 Aligned polymer network for higher corneal coverage.
Figure 7.3 Mechanism of mucoadhesion of sodium hyaluronate.
Figure 7.4 Preparation of purified alginate from brown algae.
Chapter 8
Figure 8.1 Buccal cavity.
Figure 8.2 Structure of buccal cavity.
Figure 8.3 Diffusion of bioadhesive polymer into mucous membrane.
Figure 8.4 Effect of contact angle on bioadhesive polymer adhesion.
Figure 8.5 Fracture in dosage form after adhesion with mucous membrane.
Figure 8.6 Process of bioadhesion.
Figure 8.7 Dehydration of mucus membrane and hydration of formulation.
Figure 8.8 Modified Wilhelmy Plate Apparatus.
Chapter 9
Figure 9.1 Example of mucoadhesive tablet [38].
Figure 9.2 Non-specific mucoadhesion and elimination of micro/nanoparticles ...
Figure 9.3 GI mucoadhesive patches in a capsule [3].
Figure 9.4 A microsphere patch [3].
Figure 9.5 (a) GI insulin patches in capsule, (b) insulin patches in the GIT...
Chapter 10
Figure 10.1 (a) Areas of Nasal Cavity, (b) Possible drug delivery through na...
Figure 10.2 Superior turbinate region.
Figure 10.3 Cells in human nasal epithelium. There are mainly four types of ...
Chapter 11
Figure 11.1 Transverse section of vagina [18].
Chapter 12
Figure 12.1 Advantages of nanoparticles as drug delivery agents.
Figure 12.2 Advantages of microparticles as drug delivery agents.
Figure 12.3 Advantages of liposomes as drug delivery agents.
Guide
Cover
Table of Contents
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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106
Adhesion and Adhesives: Fundamental and Applied Aspects
The topics to be covered include, but not limited to, basic and theoretical aspects of adhesion; modeling of adhesion phenomena; mechanisms of adhesion; surface and interfacial analysis and characterization; unraveling of events at interfaces; characterization of interphases; adhesion of thin films and coatings; adhesion aspects in reinforced composites; formation, characterization and durability of adhesive joints; surface preparation methods; polymer surface modification; biological adhesion; particle adhesion; adhesion of metallized plastics; adhesion of diamond-like films; adhesion promoters; contact angle, wettability and adhesion; superhydrophobicity and superhydrophilicity. With regards to adhesives, the Series will include, but not limited to, green adhesives; novel and high-performance adhesives; and medical adhesive applications.
Series Editor: Dr. K.L. MittalP.O. Box 1280, Hopewell Junction, NY 12533, USAEmail: [email protected]
Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])
Bioadhesives in Drug Delivery
Edited by
K.L. Mittal, I. S. Bakshi and J. K. Narang
This edition first published 2020 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© 2020 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
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For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
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Library of Congress Cataloging-in-Publication Data
ISBN 978-1-119-64019-6
Cover image: Pixabay.ComCover design by Russell Richardson
Preface
Even a cursory look at the literature will evince that currently there is much interest and brisk research activity in developing efficient target drug delivery routes and systems, and bioadhesives offer many virtues and advantages in this endeavor. Naturally, understanding the phenomenon of bioadhesion, i.e., its theories or mechanism (s) is of critical importance and pertinence in developing optimum boadhesive polymers (used in bioadhesives). Such bioadhesive polymers are the key for exhibiting the process of bioadhesion, controlled/sustained release of drug, and drug targeting. Use of bioadhesives restricts the delivery system to the site of interest and thus offers a useful and efficient technique for targeting a drug to the desired location for a prolonged duration. The information on this important topic of bioadhesives in drug delivery is scattered in many diverse publication media. This book addresses the various relevant aspects of bioadhesives in drug delivery in an easily accessible and unified manner, and thus fills the lacuna in the literature.
The book, containing 12 chapters by eminent researchers from many parts of the globe, is divided into three parts: Part 1: Fundamental Aspects; Part 2: Bioadhesive Formulations; and Part 3: Drug Delivery Applications. The topics covered include: Theories and mechanisms of bioadhesion; bioadhesive polymers for drug delivery applications; methods for characterization of bioadhesiveness of drug delivery systems; bioadhesive films and drug delivery applications ; bioadhesive nanoparticles; bioadhesive hydrogels and applications; ocular bioadhesive drug delivery systems; buccal bioadhesive drug delivery systems; gastrointestinal bioadhesive drug delivery systems; nasal bioadhesive drug delivery systems; vaginal drug delivery systems; and pulmonary bioadhesive drug delivery systems. It should be recorded here that all chapters were rigorously reviewed and all were suitably revised (some twice or thrice). So the material presented in this book is of archival value and meets the highest standard of publication.
The book is profusely referenced and copiously illustrated. This book should be of immense interest and usefulness to biologists, pharmaceutical scientists, polymer chemists; adhesive technologists, materials scientists and those interested in biomaterials, target drug delivery, and controlled drug delivery. Also advanced research students should find this book as a Baedeker to this immensely important area of bioadhesives in drug delivery. As more advanced and more efficient bioadhesives are developed, new application vistas will emerge.
Now comes the pleasant task of thanking all those who made this book possible. First and foremost, our sincere and heart-felt thanks go to the authors for their interest, enthusiasm, cooperation and sharing their valuable research experience in the form of written accounts, without which this book would not have seen the light of day. We will be remiss if we fail to extend our thanks to Martin Scrivener (publisher) for his whole-hearted interest in and unwavering support for this book project.
Kash MittalP.O. Box 1280Hopewell Jct., NY, [email protected]
Inderbir Singh BakshiChitkara College of PharmacyChitkara UniversityRajpura, Patiala, Punjab, India
Jasjeet Kaur NarangKhalsa College of PharmacyAmritsar, Punjab, IndiaApril 2020
Part 1FUNDAMENTAL ASPECTS
1Introduction, Theories and Mechanisms of Bioadhesion
Kamla Pathak1* and Rishabha Malviya2
1 Pharmacy College Saifai, Uttar Pradesh University of Medical Sciences, Etawah, Uttar Pradesh, India
2 Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
Abstract
Bioadhesion refers to adherence of macromolecules (synthetic and natural) to the mucosal layer of the body. The second generation bioadhesives, the biological mucoadhesives, have depicted specific interaction with biological cell surface as well as with the mucin. In this chapter, theories of bioadhesion which include wetting, diffusion, electronic, adsorption, and fracture theories have been described which are important for assessment of bioadhesion. These theories clearly explain the fundamental mechanisms of attachment and elaborate on the formation of bioadhesive bonds. This compilation also summarizes the mechanistic approach to bioadhesion which is a three-step phenomenon, namely: wetting and swelling of mucoadhesive polymer, interpenetration of polymer chains, and finally the formation of weak chemical bonds. Furthermore, various properties of mucoadhesive polymers, the mechanism(s) controlling bioadhesion, the factors affecting mucoadhesion, mucosal interaction, and biological mucoadhesives have also been elaborated.
Keywords: Bioadhesion, theories, mechanisms, factors affecting mucoadhesion, mucosal interaction, biological mucoadhesives
1.1 Introduction
Bioadhesion can be explained as the attachment of synthetic or natural macromolecules to the mucus and/or epithelial surface for extended period of time. The bond between two materials is governed by interfacial forces. Bioadhesion is quite similar to the conventional adhesion process [1]. The only difference is that bioadhesion involves special characteristics of biological organisms and surfaces. The phenomenon of bioadhesion can be classified into specific and non-specific bioadhesion [2]. The specific bioadhesion invloves mostly polymers or some biological molecules that allow the bioadhesion at cell surface or mucus. For example, lectins, the carbohydrate binding proteins derived from plant sources, have the ability to recognize a particular type of sugar molecule(s) and adhere to it. The adhesion of bacteria to the human gut may be attributed to the interaction of a lectin-like structure (present on the bacterial cell surface) and mucin. The adhering property of the lectins to the cell surface is remarkable and thus these are known to be bioadhesive. Tomato lectin is a good example of a specific bioadhesive. Tomato lectin is a complex glycoprotein that can specifically adhere to the short arrays of N-acetylglucosamine [3]. Bacterial adhesins, fimbrin, wheat germ (Phaseolus vulgaris) agglutinin, etc. are some other specific bioadhesive lectins. The non-specific bioadhesive molecules (polycarbophil, chitosan, carbopol, and carbomers) have the ability to bind with both the cell surface and the mucosal layer [4]. The property of bioadhesion has also been observed in the group of marine animals known as ascidians. The development of bioadhesives inspired from marine animals is a promising approach to generate new tissue-compatible medical components like non-fouling surfaces.
1.1.1 Historical Perspective
The use of mucoadhesive polymers for the development of pharmaceutical formulations was reported back in 1947, when attempts were made to develop a mucosal drug delivery of penicillin using gum tragacanth and dental adhesive powders [5, 6]. Improved results were reported when carboxymethyl cellulose and petrolatum were used for the development of the formulation. This research led to the development of a mucoadhesive delivery system comprising of finely ground sodium carboxymethyl cellulose, pectin and gelatin. The formulation was marketed as Orahesive® (Fagron Inc., St. Paul, MN, USA) followed by Orabase® (Colgate Oral Pharmaceuticals, Inc., USA), which is a blend of polymethylene/ mineral oil base. This was followed by the development of a system where a polyethylene sheet was laminated to a blend of sodium carboxymethyl cellulose and polyisobutylene which provided an added advantage of protecting the mucoadhesive layer by the polyethylene backing from the physical interference of the external environment [6-8].
Over the years, various other polymers, e.g., sodium alginate, guar gum, sodium carboxymethyl cellulose, poly(ethylene glycol)s, karaya gum, hydroxyethyl cellulose, methyl cellulose and retene were found to exhibit mucoadhesive property. During the 1980s poly (acrylic acid), hydroxypro-pyl cellulose and sodium carboxymethyl cellulose were widely explored for the development of mucoadhesive formulations. Since then the use of acrylate polymers for the development of mucoadhesive formulations has increased manifold. Various researchers have investigated the mucoadhesive property of different polymers with varying molecular architecture [9-11]. The voluminous research has concluded that a polymer will exhibit sufficient bioadhesive property if it can form strong intermolecular hydrogen bonds with the mucosal layer, can penetrate into the mucus network or tissue crevices, can readily wet the mucosal layer and has sufficiently long chain. When designed as a matrix (base) the mucoadhesive polymeric matrix should rapidly adhere to the mucosal layer without any change in the physical property of the delivery matrix, offer minimal interference from the release of the active agent, be biodegradable without producing any toxic by-products, inhibit the enzymes present at the delivery site, and enhance the penetration of the active agent if the active agent is meant to be absorbed from the delivery site [12].
1.1.2 Bioadhesion in Biological Systems
In biological systems, bioadhesion can be classified into three types: Type 1: Adhesion between two biological components, for example in platelet aggregation and wound healing; Type 2: Adhesion of a biological component to an artificial substrate, for example, cell adhesion to culture dishes and biofilm formation on prosthetic devices and inserts; and Type 3: Adhesion of an artificial material to a biological substrate, for example, adhesion of synthetic hydrogels to soft tissues [13]. Bioadhesion also refers to the utilization of bioadhesive materials to connect two surfaces together which can be beneficial in the surgical and dental applications. Hence, the interest in the bioadhesion research has resulted in the development of new therapies, biomaterials, and other technological products such as bio-sensors. The literature documents the use of bioadhesive polymeric systems for the development of products for various biomedical applications which include denture adhesives and surgical glue. However, bioadhesion between the materials can be deleterious as well, which is referred to as biofouling [14]. Bioadhesives can also be obtained from living organisms. Example of naturally occurring bioadhesive is mussel adhesive protein (MAP) secreted by mussel, which is comprised of multiple threads that get attached to the glass surface [15].
1.1.3 Bioadhesive/Mucoadhesive
The primary goal of development of bioadhesives is to duplicate, mimic, or improve biological adhesives. A bioadhesive material should exhibit durability of adhesion comparable to the natural bioadhesion where required, biodegradability, and non-toxicity. In pharmaceutical sciences, when the adhesive attachment is to mucus or a mucous membrane, the phenomenon is referred to as mucoadhesion. It is the adhesion of polymeric material to a mucosal membrane and is an attractive interaction between mucosal membrane and pharmaceutical dosage form [16]. The polymeric material containing an active pharmaceutical ingredient gets attached to a specifically targeted mucosa for an enhanced period of time as compared to the active pharmaceutical ingredient (API) alone. The extended API residence time on the mucosal surface increases the permeation and also the bio-availability for some APIs. It is very difficult to differentiate between adhesion of molecules to the mucus layer and adhesion of molecules to cell surface, and some bioadhesive molecules bind to both cell surface as well as to mucus layer [17].
Medical researchers deal with the pervasive aspect of the formation of biofilm and bioadhesion on solid surfaces. This phenomenon is equally applicable to catheters and contact lenses. The solid-liquid interface is of great importance because of its involvement in several biological processes. In dental applications, adhesive materials are used to treat tooth damage initiated due to caries and also to secure brackets within the teeth during the orthodontic treatment. In ophthalmology, an anti-adhesive is used in intracorneal implants and intraocular lenses. For the formulation of longer duration wear contact lenses, materials that will bind selectively to specific proteins are used for minimizing the bacterial adhesion [18].
1.1.4 Factors Affecting Mucoadhesion
1.1.4.1 Molecular Weight of Polymer
For successful adhesion, a minimum molecular weight of 100,000 daltons is required [13]. In case of a linear polymer, the adhesive property is directly dependent on the molecular weight, but in a non-linear polymer, the adhesive property may or may not depend on the molecular weight.
1.1.4.2 Concentration of Polymer Used
The concentration of polymer must be optimum. After an optimum level, the adhesive strength decreases substantially due to the separation of coiled polymeric portion so that the length of the polymer chain available for permeation becomes limited.
1.1.4.3 Flexibility of Polymer Chains
Flexibility of the polymer chains basically dictates the diffusion coefficient and viscosity. Therefore, the higher the polymer flexibility, the greater will be the diffusion in the mucus network.
1.1.4.4 Swelling
The swelling property depends on the concentration of polymer, presence of water, and the ionic strength. The polymers used in mucoadhesion need hydration to develop and form a macromolecular mesh of required size.
1.1.4.5 pH at Polymer-Mucus Interface
The pH influences the charge on the mucosal surface. The surface charges of both mucus and polymers are affected by the pH. The charge density of the mucus membrane would be different depending on the pH, because of difference in the dissociation of functional group on carbohydrate and amino acids of the polypeptide.
1.1.4.6 Mucin Turnover Rate
High turnover of mucin occurs most of the time but it is not beneficial because it limits the residence time of the adhesive polymer. The polymer tends to detach from the mucus layer even though the polymer bears good bioadhesive property.
1.1.4.7 Stereochemistry
The electron-rich groups such as -OH, -COOH etc. are present in many bioadhesive polymers. These groups cause electronic cloud over functional groups that may be active and responsible for adhesion. The molecular configuration dictates the extent of interaction between the substrate and polymer. Additionally, the orientation of molecules is also responsible for the overall lowering of free energy after binding. Figure 1.1 presents a schematic diagram depicting the factors affecting mucoadhesion.
Figure 1.1 Various factors affecting mucoadhesion.
1.2 Bioadhesive Interactions
The bonding and attachment between adhesive polymers and biological surfaces generally occurs via interpenetration followed by secondary non-covalent bonding between them. It has been found that the secondary bonding mainly occurs via the formation of hydrogen bonds [19]. The bioadhesive polymers possess hydrophilic functional groups such as hydroxyl (-OH), sulfate (-SO4H), carboxyl (-COOH), and amino groups (-NH2) that can be considered favorable for target delivery. Therefore, mainly the hydrogen bonds contribute to the formation of a strong network. So the polymers that possess a high amount of hydrogen bonding groups can interact more strongly with the glycoproteins. Polymers that can be used as bioadhesives and can easily get adhered to the mucin epithelial surface should possess the following characteristics. Firstly, the polymer must be adhesive in nature so that it adheres when placed in water. Secondly, it should attach non-specifically, and non-covalently, and thus non-covalent interactions must occur for adhesion. Lastly, the polymer should bind specifically to the receptor sites on the cells or mucosal surfaces. The desirable key attributes of bioadhesive polymers include high molecular weight, appropriate surface tension to spread on mucus layer, and anionic surface charge [20].
1.3 The Mechanistic Approach to Bioadhesion
The mechanistic approach to bioadhesion can be related to the polymer based on its physico-chemical properties [21]. The three fundamental steps during the mucoadhesive process are as follows: firstly the wetting and swelling of the polymer should allow an intimate contact with the tissue; secondly, the interpenetration of the polymer chains and entanglement between the polymer and the mucin chains should be attained; and finally, the formation of weak chemical bonds should be possible [22]. The polymeric hydrogels also exhibit mucoadhesive property. Hydrogels possess enhanced mucoadhesive property and based on this property, the characteristics that define hydrogel as a promising system include: the presence of a high amount of hydrogen bonding chemical groups, such as hydroxyls and carboxyls, anionic surface charge, high polymer molecular weight, and high polymer chain flexibility. These characteristics induce spreading of hydrogels onto the mucus layer.
There are three main types of interactions between a polymer and the mucous layer. They are physical or mechanical bonds, secondary chemical bonds, and covalent chemical bonds. Physical bonds imply the entanglement of mucin glycoproteins with the polymer chains and the interpenetration of the mucin chains in the polymer matrix. This interpenetration of macromolecules will depend on their respective chain flexibilities and diffusion coefficients. Secondary chemical interactions include, van der Waals interactions and hydrogen bonding. Hydrogen bonding is probably the most important secondary chemical interaction in mucoadhesion because it forms link between the functional groups and the mucoadhesive polymer. Some of the functional groups such as hydroxyls, carboxyls, sulfate and amino groups involved in hydrogen bond formation will establish good mucoadhesive property. The polymers such as poly (vinyl alcohol), poly(acrylic acid), poly(hydroxyalkyl methacrylate) have shown good mucoadhesive property in the past. Formulations possessing mucoadhesive property can increase the retention time of dosage forms in the GI tract [23]. Even these types of forces are weak and only numerous interaction sites lead to strong mucoadhesion. Additionally, covalent bonds may form by chemical reaction between the mucoadhesive polymer and the mucus substrate. Though a stable bond is permanent, the mucus turnover and the epithelial desquamation would result in the detachment and loosening of the polymer from the tissue [24, 25].
1.4 Factors Controlling Bioadhesion
The mechanism of biological adhesion is controlled by various key factors that can be classified into four broad categories. These include chemical interactions, surface morphology, physiological factors, and physical or mechanical bonds.
1.4.1 Chemical Interactions
Chemical interactions between the protein and the surface are influenced by the charges on both protein and surface. The interaction between chemically active surfaces promotes the adhesion process. If the two chemically active surfaces are able to form bonds like covalent or ionic, then strong adhesion can occur. Similarly, if the mating surfaces form weak bonds such as dipole-dipole, hydrogen bonding or induced dipoles, then weaker adhesion will occur [26-28].
Interestingly, studies on the interaction between protein and solid surfaces have led to the assumption of uniform surfaces and existence of only a single type of interaction between the surface and protein. The strength of protein adsorption relies on polarity and the net charge on the protein. The protein and substrate can be positively charged, negatively charged, hydrophobic, or neutral hydrophilic. The bonding of a neutral hydrophilic portion of protein with the biological surface which possesses almost the same polarity is the basic reason behind weak adsorption mechanism [29]. Moderate adsorption occurs when there is ionic interaction between proteins and substrate surfaces. However, strong adsorption occurs only when the interactions occur between hydrophobic protein moieties and the substrate. Specific examples to illustrate chemical interactions are detailed below.
1.4.1.1 Mussel Adhesion
Mussel adhesion is one of the examples that show how the chemical composition of the surface changes the adhesion mechanism. The interaction between mussel and the underwater surfaces that involves the removal of weak layers (mostly water) occurs in two ways. In the first case, the underwater surface is non-polar. So, the water boundary layers interact via weak dispersion forces. Because the mussel adhesive protein is larger than the water molecule, the protein experiences larger dispersion interaction with a non-polar surface that leads to the removal of boundary water layer and adhesion of the protein (Figure 1.2). In the second case where the underwater surface is polar, the boundary layer of water cannot be easily displaced. So in this case the mussel adhesive protein utilizes its hydrophilic amino acid side chains, which consist of groups like aminoalkyl, hydroxyalkyl, phenolic to form strong hydrogen bonds. Therefore, the mussel adhesive protein is capable of displacing water and gets adhered to polar underwater surfaces as well [30, 31].
Figure 1.2 Interaction between water molecules and mussel adhesive protein.
1.4.1.2 Cell Adhesion to Biomaterials
Adhesion of cells to biomaterial surfaces is a complex phenomenon. It has been found that the microscale surface topography has a direct impact on cell proliferation and adhesion. The composition of chemical present on biomaterial surfaces plays an important role in the cell proliferation process and cell adhesion. Cell adhesion is affected by the integral group of cell surface receptors and thus it depends on the structural conformation of the extracellular matrix protein which seems to be sensitive to the surface [32].
1.4.2 Surface Morphology Effects
The adhesion of cells to the surfaces of synthetic biomaterials is significant in the designing and performance of body implants. When a biomaterial is placed into a living host, cells are not directly connected to the biomaterial surface. Instead, the biomaterial is enclosed into a protein layer. Various models have been utilized to study surface morphology effects on cell adhesion and on protein conformation [33]. Micro/nanoscale topography is important to characterize the adhesion of cells to biomaterials which is attained by different approaches. The first approach is the top-down or lithographic method or also known as a dry etching method. The second approach is the bottom-up or self-assembly process [34].
1.4.3 Physiological Factors
Physiological factors also play a significant role in bioadhesion and are important in surgical procedures, e.g. when fibrin tissue adhesive is used in surgical applications. This adhesive is applied below the dermis for skin grafts, flaps and also for laparoscopic surgeries. These adhesives are generally packed in two different packages, which are mixed during the surgery. One package contains fibrinogen, plasma glutaminase and calcium chloride. The second package contains thrombin and anti-fibrinolytic agent. This bioadhesive works on the basis of the physiology of the blood coagulation process. Thrombin divides the protein fibrinogen into smaller subunits of fibrin during clotting. The smallest unit is fibrin which causes end-to-end polymerization. The cross-linking of subunits of fibrin results into clot formation in the presence of calcium [35, 36].
1.4.4 Physical and Mechanical Factors
The physical and mechanical factors in bioadhesion are generally affected by the interaction between the polymer chain. Wetting and interpenetration are the two factors that affect physical and mechanical interactions.
1.4.4.1 Wetting Phenomenon
For successful bioadhesion, interfacial free energy is an important determinant. In systems where bioadhesion takes place, the liquid environment plays an important role. The liquid environment influences the spreading of one material over another; for example, adherence of the adhesive polymer to the mucous layer of a biological membrane which is immersed in a liquid medium. At the time of adhesion, an interface between mucus, liquid and the polymer is formed and the liquid layer disappears thus forming a bond between polymer and mucus layer [37].
1.4.4.2 Interpenetration
In the initial stages of bioadhesion, interfacial contact and chemical bonding phenomena are the important considerations to maintain bioadhesion. On the other hand, the adhesive bond will be maintained by interpenetration of molecules between the two contacting surfaces. In the two contacting surfaces, if one is considered as a polymer which is involved in the process of adhesion then the inter-diffusion process involves the property of the single chains and their involvement in the opposing membrane. Similarly, in the case of the swelling polymers the inter-diffusion process is governed by the ratio of wet and dry weights [38].
1.5 Theories of Bioadhesion
The important parameters for assessing mucoadhesion are: (i) mucus substrate characteristics, (ii) composition of mucoadhesive material, (iii) functional characteristics of the substrate, and (iv) associated applied force between the mucoadhesive and the mucosal surface or the biological surface [39]. Bonding involved in the process occurs chiefly through both physical and weak chemical bonds. Physical or mechanical bonds result from entanglement of the adhesive material and the extended mucus chains. In this regard, mutual diffusion of the mucoadhesive polymer and mucin chains will result in the maximum attachment. Chemical bonding may be classified as a primary or secondary type. Primary bonds are due to covalent bonding while secondary bonds may be due to electrostatic, hydrophobic, or hydrogen bonds. Electrostatic interactions and hydrogen bonding appear to be important as a result of a large number of charged species e.g., hydroxyl (-OH), carboxyl (-COOH) and amino (-NH2) groups present on the mucosal surface. Hydrophobic bonding occurs when non-polar groups associate with each other in an aqueous solution due to the tendency of water molecules to exclude non-polar molecules. The van der Waals attraction between hydrophobic groups has binding energies between 1-10 kcal/mol, whereas hydrogen bonds between hydrophilic groups have energy of about 6 kcal/mol. Hydrophobic bonding is generally considered to be a key factor in bioadhesion. There are various putative theories in general to explain the fundamental mechanism(s) of attachment [40, 41]. In a particular system, one or more theories (wetting, diffusion, electronic, adsorption and fracture) can equally explain or contribute to the formation of bioadhesive bonds [42].
1.5.1 Wetting Theory
It is one of the oldest and well established theories of adhesion. This theory best describes the adhesion of liquids or low viscosity bioadhesives to a biological surface. The adhesion can be expressed in terms of surface and interfacial tensions [41]. When an interface is formed, there is a release of energy per cm2 that can be defined as the work of adhesion. The wetting theory deals with the contact angle and the thermodynamic work of adhesion [43]. The work of adhesion is given by Dupre’s equation (1.1) [13]:
Where Wa is the specific thermodynamic work of adhesion and γa, γb, and γab represent, the surface tension of the bioadhesive polymer, surface tension of the biological substrate, and the interfacial tension between the polymer and substrate, respectively. The work of cohesion is represented by equation (1.2):
When a bioadhesive material (a) spreads on a biological substrate (b), the spreading coefficient can be calculated by the following equation (1.3),
The value of Sa/b should be positive for the bioadhesive material to spread on the biological substrate. When a bioadhesive liquid a, spreads on the biological substrate b, the contact angle is given by equation (1.4).
Figure 1.3 shows the key components involved in spreading of bioadhesive liquid over a soft tissue surface [44].
Figure 1.3 Spreading of bioadhesive liquid over a typical soft tissue surface.
1.5.2 Diffusion Theory
According to this theory, the polymer chains bind to the mucus and comingle to a sufficient depth to create a semipermanent adhesive bond [45]. There is a close interaction of contact between the bioadhesive material and glycoprotein (present in the mucus membrane). The polymer chains penetrate the mucus; the exact depth to which these penetrate to achieve sufficient bioadhesion depends on the diffusion coefficient, time of contact, and other experimental variables. The diffusion coefficient depends on molecular weight and decreases rapidly as cross-link density increases [46]. This suggests that the flexibility and chain segment mobility of the bioadhesive polymer and mucus glycoprotein molecules are important parameters to control inter-diffusion. During chain interpenetration, a concentration gradient is established. The bioadhesive polymer chain penetration depends on the diffusion coefficient of the macromolecule and the chemical potential gradient. In the case of cross-linked polymers, the interpenetration of large chains occurs with great difficulty [47]. The exact penetration depth needed for good bioadhesive bonds is not clearly established, but it is estimated to be in the range of 0.2–0.5 μm. The mean diffusional depth (s) of the bioadhesive polymer segments is calculated by equation (1.5),
Where D is the diffusion coefficient and t is the contact time. Figure 1.4 is a schematic diagram for interdiffusion of the polymer chain and mucin chain.
Figure 1.4 Interactions resulting from inter-diffusion of polymer chains of bioadhesive system and mucus membrane. (a) Polymer chains before diffusion, (b) contact between polymer chains and mucin chains and (c) inter-diffusion of mucin chains and polymer chains.
1.5.3 Electronic Theory
According to this theory, transfer of electrons takes place when an adhesive polymer comes in contact with a mucus glycoprotein network because of differences in their electronic structures. This leads to the formation of an electrical double layer at the interface. Such a system behaves analogously to a capacitor, which is charged when two surfaces come in contact, and discharged when they are separated [19]. This theory is also applicable since both the biological substrate and the mucoadhesive material possess some electrical charges that are opposite to each other. Therefore, when these two materials come in contact, they transfer electrons, which form the electrical double layer at their interface. The attractive force present within this newly formed electrical double layer determines the mucoadhesive strength [1].
1.5.4 Adsorption Theory
According to this theory, after the initial contact of the two surfaces, the materials will adhere because of the surface forces acting between the atoms in the two surfaces. According to this theory, after the initial contact of the two surfaces, the mucoadhesive material will adsorb on the biological surface due to forces acting between them. In adsorption, the weak forces like van der Waals interaction play an important role at the interface [39]. The chemical bonds include primary and secondary bonds. Primary chemical bonds (covalent in nature) are undesirable in bioadhesion because of their high strength that causes the formation of permanent bonds. Secondary chemical bonds involve forces of attraction, including electrostatic forces, van der Waals forces and hydrogen and hydrophobic bonds [19].
1.5.5 Fracture Theory
The fracture theory of adhesion is related to the separation of two surfaces after adhesion [48]. The fracture strength σ is directly proportional to adhesion strength and is given by the following equation (1.6),
Where E is Young’s modulus of elasticity, ε is the fracture energy, and L is the critical crack length when two surfaces are separated. The work done by an elastomeric network to cause fracture, Gc, can be expressed as equation (1.7):
Figure 1.5 Regions that represent rupture of the mucoadhesive bond.
K is a constant which depends on the density of the mucoadhesive polymer, effective mass, length, the flexibility of a single mucin chain bond, and bond dissociation energy. Gc of an elastomeric network increases with molecular weight Me of the network strands [49]. Figure 1.5 is a schematic representation of the rupture of mucoadhesive bonds [50].
1.6 Stages of Mucoadhesion
For a better understanding of the broad concept of mucoadhesion, the process of mucoadhesion can be differentiated into three stages: wetting, interpenetration, and interaction of mucoadhesive with biological substrate. The mucoadhesive must wet the substrate to develop an intimate contact between the mating partners. The hydrophilic property of the mucoadhesive polymer is an important consideration in mucoadhesion because mucoadhesive interaction occurs in the presence of water (mucus consists of 95% water) [51]. Low contact angle between water and the polymer will encourage the hydration of the mucoadhesive polymer chains and increase the segmental mobility. Spreading of the mucoadhesive polymer over the mucus also promotes intimate contact. So, it is important that the mucoadhesive polymer chains are able to diffuse into the mucus network so that interdigitation between the interacting materials may occur. The mucoadhesive polymer must have an enough linear chain length to ensure interpenetration during mucoadhesion [51]. The segmental mobility of the mucoadhesive polymer chain is of great importance in inducing entanglement between the interacting agents. The proposed mechanism of adhesion of hydrocolloids suggests that upon hydration the synthetic mucoadhesive polymer molecules become more mobile and are even able to orient themselves at adhesive sites of the substrate. As the level of hydration increases, adhesion strength reduces since the mucoadhesive bonds become more extended. Based on the rate of diffusion of mucoadhesive polymer through mucus networks and the depth of penetration required for mucoadhesion, interdigitation alone cannot account for the mucoadhesive interaction because of the time dependency of the process. Therefore, secondary bond formation is assumed to play a significant role. Mucus layer acts as defensive covering to protect cells and control drug delivery.
1.7 Modulation of Mucoadhesion
A large number of variables influence the chemical and physical attributes of the mucin or mucoadhesive polymer that affect the extent of mucoadhesion. Depending on the mucoadhesive polymer, there is the possibility to modulate the mucoadhesive property of the complex system [52]. Surface free energy modulation can influence the interaction of mucin with mucosal liquids as listed below [53]:
Various substances interact with the mucin and are known as mucous thickening/thinning agents. Accumulation of agent (thickening/thinning) depends upon electrostatic charges and composition of the mucin.
Calcium precipitates mucin, and when mucin is used to vary the tonicity (osmotic pressure gradient) of the medium, it decreases shear stress. A higher value of shear stress shows better bioadhesion between polymer and mucus.
The level of hydration of mucoadhesive declines with a consequent reduction in tensile stress, and thus expanding the ionic nature of the medium.
The mucin can be altered by the action of mucolytic agents. The mucolytic agents decrease the thickness of mucus by adjusting the organization of mucus through a burst of disulfide bonds or by the proteolytic activity of the catalyst. Disulfide bond breaking leads to splitting of the disulfide bridges.
Structural breakdown of the mucus polypeptide by sodium deoxycholate and lysophosphatidylcholine.
Duodenogastric reflux causes alteration in the structure of mucin and leads to gastric ulcer.
Some disease states disturb the integrity of the mucin layer. For example, ulceration and irritation of the digestive system cause rupture of the mucin layer, while cystic fibrosis causes thickening of the mucin layer and may lead to hindrance to bronchi [
54
].
1.8 Adhesion Promoters
Adhesion promoters are used for the improvement of mucoadhesion. Adhesion promoters are used to modulate the macroscopic adhesion property of engineered hydrogels and affect the polymer chain dispersion. Tethered polymer chains are polymer chains with one of their terminals appended to a 2-dimensional surface. Attaching of long polychains on polyhydrogels and their copolymers can be accomplished by grafting reactions or by copolymerization. The hydrogels display mucoadhesive property because of enhanced anchoring of the chains with the mucosa. Engineered hydrogels include many distinguishing features: (i) one of their terminals is covalently bonded with the hydrogels that tends to increase the quality of adhesion bond, and (ii) charge of the tethered chains imparts capacity to cling to the surface [18].
1.9 Surface Free Energy Analysis of Bioadhesion
Surface free energy is an important physicochemical property responsible for bioadhesion. The surface offers the opportunity for potential bonds because the molecules and atoms present at the surface can react with the same or different types of atoms and molecules [55]. When water interacts with the surface molecules/atoms, it alters the surface free energy. Interactions occur through hydrogen bonds, van der Waals interaction, hydrophobic interaction, electrostatic and polar interaction. The work of adhesion can thus be explained as the work needed to detach the adhesive from the substratum and is equivalent to the sum of surface tension of liquid and surface free energy of solid minus interfacial free energy between the liquid and solid. It has been studied that the increase in the concentration of dihydroxyphenylalanine (DOPA) increases the bioadhesive interaction [56].
The literature depicts that biomaterials are utilized for cardiovascular devices. The main problem in the establishment of biocompatibility of cardiovascular devices is the interfacial interaction between biomaterial and blood. The reports by researchers also depict that there exists a relation between implant surface free energy, blood flow and thrombosis. High surface free energy promotes bioadhesion [55, 57].
1.10 Molecular Biology in Bioadhesion
In the field of molecular biology, bioadhesion refers to the ability of a living organism to adhere to a surface either permanently or temporarily. Molecular biology is beneficial in bioadhesion in terms of isolation of genes, the study of gene expression and gene function [58]. Tremendous research in recent years has led to advances in the sequencing of DNA, RNA as well as in the analysis of proteins. These recent advancements in technologies motivate the researchers to shift their study from a single gene to complete sets of genes followed by examining the genes that are expressed at a time. The advancements in molecular biology provide a large number of research techniques and devices that are productive for the researchers who may work on bioadhesion involving certain particular organisms. The bioadhesion research is based on the techniques used in biochemistry, histology and mechanics but there are certain model approaches for molecular biology [59]. The models are mussels, barnacles, sandcastle worms, flatworms, starfishes, etc. However, there are four different steps that show how to narrow the number of candidate transcripts involved in adhesion. These steps include (i) generation of transcriptome and differentially expressed cDNA that is enriched in adhesion-related transcripts; (ii) setting up a basic local alignment search tool (BLAST); (iii) performing an in-situ hybridization screen, and (iv) functional analysis of selected genes using RNA interference. These steps are detailed below.
For the generation of a transcriptome that consists of only adhesion-related genes of a living organism, it is very necessary to select only the particular type of tissue that contains bioadhesive organs. Selection of proper bioadhesive organs is necessary to minimize the complexity of the transcriptome while expressing genes and minimizing the cost. The steps for the generation of a transcriptome include isolation of total RNA and selection of polyRNA. After selection, the next step is fragmentation of RNA into 200-300 base pairs and reverse transcription into complementary DNA [60]. Then, sequencing adapters bind chemically by a standard protocol. On the other hand, strand-specific sequencing can be executed. Selection of particular size range base pairs (200) followed by polymerase chain reaction-based amplification leads to the generation of DNA [61]. Finally, bioinformatic data analysis is done which includes error correction, de-multiplexing, artifact removal, etc. In the end, all the data are assembled into a hypothetical transcript that finally results in the transcriptome of the organism that was selected [62].
Next is setting up a basic local alignment search tool (BLAST) which is basically a software for the analysis of sequence databases. This software has been widely used to find candidate genes for analysis by utilizing molecular approaches. From this software, adhesion-related transcripts of the organism can be analyzed as well as mass spectrometry results for peptide sequences can be compared with the predetermined transcriptome database [63].
In situ hybridization is a ubiquitous and simple method to detect the spatial and temporal genes expression present within a tissue. The purpose is to investigate different kinds of nucleic acids. The principle of in situ hybridization includes pretreatment (by paraformaldehyde and proteinase K) of the tissue or the organism with an adhesive organ that consists of staining the organisms [64]. After pretreatment of the tissue, digoxigenin-labeled RNA probe is added which gets bound to the complementary messenger RNA. The bound products are analyzed via an antibody (anti-digoxigenin complex) formation. Nitro blue tetrazolium chloride is added that leads to the formation of blue color in cells because of the bound anti-digoxigenin antibody. The blue staining reveals that the cells with the target gene expression are present in the adhesive organ. For evaluating whether a transcript is expressed into an adhesive organ of the organism or not, functional analysis of both protein and the gene is necessary. Of the various techniques to detect the role a gene, RNAi gives fast and direct results.
1.11 Bioadhesives from Marine Sources
The process of developing bioadhesives from marine animals is a promising strategy for generating new materials like advanced glues or fouling-resistant surfaces. To develop advanced glues or fouling-resistant surfaces, it is important to know about the structural, mechanical and molecular properties of the adhesive organs of selected species. Ascidians (sea squirts) are the groups of marine organisms that are considered interesting in the context of bioadhesion. The ascidians are important foulers, and the larvae as compared to adult ascidians show adhesive property. The ascidians are also important for the stepwise building of adhesive organ at both cellular and molecular levels [65]. Ascidians that develop adhesives are mostly marine vertebrates. This property results in their attachment to any surface that may undergo metamorphosis and results in permanently sessile adults [66]. They are popular as model organisms for developmental biology [67]. Adhesives developed from marine organisms can be useful in the medical field because these have distinctive ability to cure in wet environments and are also compatible with the tissues. Formation of multicomponent bioadhesives in marine organisms helps in their survival in unfavourable environmental conditions [68].
The secretions from the adhesive animals are based on proteins and vary widely between different adhesive organisms. As mussel byssus and barnacle have maximum adhesive secretions and contain different types of adhesive proteins. In the case of adult mussels, they bind to the surfaces after secreting a bundle of threads from the glands present in the foot of mussel. The first two proteins that are secreted on the surface of the substrate are Mfp/3 and Mfp/5. These proteins contain a high content of 3,4-dihydroxyphenyl-L-alanine (DOPA) [68]. However, in biomimetic engineering, catechol components that duplicate adhesive property are functionalized with synthetic polymers that possess sealant, coating and adhesive properties.
1.12 Mucoadhesive Drug Delivery Systems
These days mucoadhesion is garnering considerable attention for development of safe and useful commercial dosage forms. While single unit mucoadhesive dosage forms are yet to place themselves, particulate drug delivery systems like microparticles, microspheres, nanoparticles or liposomes have demonstrated some interesting and useful features like uniform circulation at the target site and reproducible medication adsorption [69, 70]. Different drug delivery carriers based on the mucoadhesive property of the polymers are discussed in the other chapters in this book.
1.13 Summary
An understanding of the fundamental mechanisms that govern bioadhesion is of great interest for researchers in various fields. One area of research focuses on natural adhesive materials produced by or extracted from plants, animals, fungi and bacteria. The second area of research in the field of bioadhesives focuses on man-made materials that aim to mimic the remarkable adherence capability of natural adhesives. To date, a variety of materials have been fabricated that find applications in drug delivery. The term mucoadhesion may be used synonymously with bioadhesion to describe these systems. The concept of bioadhesion opens a new area of research in the biomedical sciences and attracts pharmaceutical industries to develop new formulations for improved therapeutic effects.
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