Mucoadhesive Materials and Drug Delivery Systems

Vitaliy V. Khutoryanskiy

• Publisher: Wiley
• Year: 2014
• Print ISBN:
  9781119941439
• eBook ISBN:
  9781118794395
• Edition: 1
• Topic: Scienze fisiche
• Subtopic: Chimica organica

Mucoadhesion defined as attachment of synthetic or natural materials to mucosal tissues has been widely exploited in pharmaceutical forms. This multi-author book provides an up-to-date account of current research on mucoadhesive materials and drug delivery systems. The introductory section describes the structure and physiology of various mucosal surfaces (oral, nasal, ocular, gastrointestinal and vaginal mucosa). This is followed by chapters on the various methods used to study mucoadhesion and to characterise mucoadhesive properties of various dosage forms. The final section will summarise information on traditional and novel types of mucoadhesive materials, such as chitosan, thiomers, and liposome-based formulations.

This book is unique as there is currently no modern book considering mucoadhesion - all other existing books on the topic are either narrowly focused or more than 10 years old. Furthermore, each contributor offers specialist perspectives from a variety of global locations in both industrial and academic research centres.

Section One
Structure and Physiology of Mucosal Surfaces in Relation to Drug Delivery

1
Oral Mucosa: Physiological and Physicochemical Aspects

Gleb E. Yakubov^1,2, Hannah Gibbins³, Gordon B. Proctor³ and Guy H. Carpenter³

¹School of Chemical Engineering The University of Queensland Australia

²Australian Research Council Centre of Excellence in Plant Cell Walls The University of Queensland Australia

³Salivary Research Unit King's College London Dental Institute UK

1.1 Anatomical and Histological Aspects of Oral Cavity Tissues

1.1.1 Tissue Architecture

Like no other mucosae, the oral cavity comprises the widest range of different tissues and types of mucosal linings. The oral cavity comprises soft oral tissues of gums, buccal surfaces, hard palate, the tongue, and lips. Teeth are by contrast made of biomineralised material with outer enamel containing up to 96% hydroxyapatite, with water and protein accounting for the remaining 4%. Such diversity stems from the multiple physiological functions of the mouth and environmental stresses that it is subject to. Temperature variations, mechanical action, food processing, defence against microorganisms and toxins (e.g. nicotine) are some of those environmental conditions that oral surfaces cope with to provide key physiological functions, such as the digestive, sensing, protective and barrier functions of the underlying tissues, pathogen resistance and immunity.

The epithelium of the mouth varies considerably. In areas of high abrasion, such as the hard palate and the tongue, the top layer of epithelial cells is highly keratinised and the rete processes that hold the lamina propria to the epithelium are more apparent (Figure 1.1). In other areas, such as the cheek and under the tongue, the epithelium is not so keratinised. Oral epithelium is comprised of tightly packed layers of epithelial cells originating from the basal layer. As cells proliferate from the basal layer they start to differentiate into larger flattened squamous epithelial cells. As part of the differentiation process cells increase levels of intracellular transglutaminase. This enzyme helps to cross-link proteins within the cell into the cell wall, forming a tough proteinaceous coat that is impermeable to water and osmotic changes. Under the basal layer of epithelial cells is the lamina propria containing a rich capillary bed and fibroblasts forming the connective tissue (collagen). Depending on the location, function and proximity to the external environmental, the mechanical strength and permeability of oral mucosa may exhibit considerable variation. This variation is typically achieved through the level of keratinisation within the epithelium. The keratinised tissues (i.e. masticatory mucosa) are relatively tough, for example the hard palate and gums where the granular layer is enriched with keratin filaments. The nonkeratinised tissues (i.e. mucosal linings) are softer and more permeable, for example the floor of the mouth and buccal (i.e. cheek) surfaces. The tongue is an example of specialised mucosa; it consists of both keratinised and nonkeratinised regions. The raised bumps seen on the tip of the tongue are keratinised and have occasional taste buds. However, most taste buds are present further back on the tongue within the circumvallate papilla. The permeability of oral mucosa depends on the level of keratinisation, thickness and lipid content. The lipid content of keratinised oral tissues has some distinctive patterns compared to skin. The hard palate epidermis contains about 10-fold lower levels of cholesteryl esters and linoleate-rich acylceramide (CER1), and a 10-fold higher level of triacylglycerols. The palate epidermis also contains some significant amounts of phospholypids, such as sphingomyelin, phosphatedylcholine and phosphatedylserine, that are totally absent in the skin epidermis. Despite being less permeable compared to nonkeratinised linings, keratinised oral tissues are still some 10 times more permeable than skin due to lipid composition and the level of hydration. The thickness of the epithelium in the oral mucosa also varies, with the buccal mucosa having a 580 ± 90 μm thick epithelium compared to a 190 ± 40 μm thin epithelium of the floor of mouth (for comparison the thickness of typical skin epidermis is in the range between 100 and 120 μm). For mucoadhesive applications it is also important to consider that turnover rate is higher for nonkeratinised tissues than for keratinised ones [1–6].

Figure 1.1 Section of human hard palate mucosa stained by haematoxylin and eosin. The purple-stained epithelium overlies the pink lamina propria and the submucosal layer. (Image courtesy of Prof Peter Morgan, King's College London, UK.)

Many mucosal surfaces act as an ecological niche for microorganisms, and oral cavity is not an exception. In fact, it hosts a unique and complex microbial ecosystem, with up to 10 000 microbial species belonging to firmicutes, bacteroidetes, proteobacteria and actinobacteria phyla in the ratio approximately 40 : 30 : 20 : 5, with the remaining ∼5% being other bacterial phyla, candida fungi and some protozoa. Bacterial species are represented by both aerobic and anaerobic species (e.g. Fusobacterium nucleatum), with survival of the latter depending on their association with aerobic species [7].

The current review focuses on the structure and function of mucosa on soft oral tissues, since soft surfaces are key targets for oral transmucosal drug carriers. For a comprehensive review on oral microbiology the reader is referred to a book by Marsh and Martin, [8], and for a more detailed account of tooth surfaces and salivary tooth pellicle to a recent edition of ‘Oral Biology’ by Berkovitz [9].

1.1.2 Innervation

The mouth is richly innervated mostly by sensory nerves although some autonomic efferents innervate the blood vessels and the minor salivary glands. The sensory nerves innervate the mucosa to detect touch, temperature, damage and tastes. The facial nerve (cranial nerve (CN VII), the glossopharyngeal nerve (CN IX), and the trigeminal nerve (CN V) innervate the oral cavity [10]. Taste buds in the posterior one-third of the tongue receive innervation from the glossopharyngeal nerve, while those in the anterior two-thirds receive innervation from the chorda tympani branch of the facial nerve [11]. Specifically, chorda tympani fibres innervate fungiform papillae and the facial nerve fib...

Table of contents

• Cover
• Title Page
• Copyright
• About the Editor
• List of Contributors
• Preface
• Section One: Structure and Physiology of Mucosal Surfaces in Relation to Drug Delivery
• Section Two: Understanding of Mucoadhesion and Methods of Investigation
• Section Three: Mucoadhesive Materials
• Index
• End User License Agreement