Bioadhesives in Drug Delivery

K. L. Mittal, Inderbir Singh Bakshi, Jasjit Kaur Narang, K. L. Mittal, Inderbir Singh Bakshi, Jasjit Kaur Narang, K. L. Mittal, Inderbir Singh Bakshi, Jasjit Kaur Narang

• Publisher: Wiley-Scrivener
• Year: 2020
• Print ISBN: 9781119640196
• eBook ISBN: 9781119640264
• Edition: 1
• Topic: Technology & Engineering
• Subtopic: Materials Science
• Index: Technology & Engineering

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.

Part 1
FUNDAMENTAL ASPECTS

1
Introduction, 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 durabilit...

Table of contents

• Cover
• Table of Contents
• Preface
• Part 1: FUNDAMENTAL ASPECTS
• Part 2: BIOADHESIVE FORMULATIONS
• Part 3: DRUG DELIVERY APPLICATIONS
• Index
• Also of Interest
• End User License Agreement