Drug Delivery Aspects

Volume 4: Expectations and Realities of Multifunctional Drug Delivery Systems

Ranjita Shegokar

• Publisher: Elsevier
• Year: 2020
• Print ISBN: 9780128212226
• eBook ISBN: 9780128218501
• Topic: Tecnologia e ingegneria
• Subtopic: Biotecnologia in medicina

Drug Delivery Aspects reviews additional features of drug delivery systems, along with the standard formulation development, like preclinical testing, conversion into solid dosage forms, roles of excipients and polymers used on stability and sterile processing. There is a focus on formulation engineering and related large scale (GMP) manufacturing, regulatory, and functional aspects of drug delivery systems. A detailed discussion on biologics and vaccines gives insights to readers on new developments in this direction.The series Expectations and Realities of Multifunctional Drug Delivery Systems examines the fabrication, optimization, biological aspects, regulatory and clinical success of wide range of drug delivery carriers. This series reviews multifunctionality and applications of drug delivery systems, industrial trends, regulatory challenges and in vivo success stories. Throughout the volumes discussions on diverse aspects of drug delivery carriers, such as clinical, engineering, and regulatory, facilitate insight sharing across expertise area and form a link for collaborations between industry-academic scientists and clinical researchers.Expectations and Realities of Multifunctional Drug Delivery Systems connects formulation scientists, regulatory experts, engineers, clinical experts and regulatory stake holders. The wide scope of the book ensures it as a valuable reference resource for researchers in both academia and the pharmaceutical industry who want to learn more about drug delivery systems.- Encompasses engineering and large-scale manufacturing of nanocarriers- Considers preclinical, regulatory and ethical guidelines on nanoparticles- Contains in-depth discussions on delivery of biologics, vaccines and sterilisation- Industrial view on solid dispersions, milling techniques

Chapter 1

Versatile hyaluronic acid nanoparticles for improved drug delivery

Mona M.A. Abdel-Mottaleb^a,b; Hend Abd-Allah^a; Riham I. El-Gogary^a; Maha Nasr^{a a} Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
^b PEPITE EA4267, Univ. Bourgogne Franche-Comté, Besançon, France

Abstract

Hyaluronic acid's (HAs) amazing characteristics, including its consistency, biocompatibility, and hydrophilicity, have made it an excellent ingredient in cosmetic dermatology and skin-care products. Moreover, its unique viscoelasticity and limited immunogenicity augmented its use for viscosupplementation in osteoarthritis treatment, as a surgical aid in ophthalmology, and for surgical wound regeneration in dermatology. In addition, HA has currently been explored as a drug delivery agent for different routes such as nasal, pulmonary, ophthalmic, topical, and parenteral. Hence the use of nanotechnology would combine the outstanding properties of HA with the different advantages of nanoparticles such as enhanced therapeutic effects and targetability. In this chapter, the use of HA nanoparticles as a versatile drug delivery system are discussed by highlighting the different production techniques based on the chemical and biological properties of HA, as well as considering some of the their prominent medical applications.

Keywords

Hyaluronic acid; Nanoparticles; Skin; Tissue regeneration

1 Introduction

Although more than 80 years have passed since the discovery of hyaluronic acid (HA), it still surprises researchers with its unique physicochemical properties and physiological roles in the human body. HA was first discovered by Karl Meyer and John Palmer in 1954 [1]. They isolated an unknown material from the vitreous bodyof a bovine eye, containing two sugar molecules including “uronic acid.” So, by connecting the substitute name for the vitreous—“hyaloid”—with the name of a component of that polysaccharide—“uronic acid”—the name of HA was adopted for this material. HA was first used commercially as a substitute for egg white in bakery products. Later on, its first medical application for humans was initiated as a vitreous replacement during eye surgery in the late 1950s [2].

HA belongs to a group of substances called mucopolysaccharides belonging to the glycosaminoglycans (GAGs) family [1, 2]. HA includes several thousand repeating disaccharides molecules in the backbone. The molecular weight of HA molecules differs owing to the variable number of these repeating disaccharide units in each molecule, its molecular weight ranges from 1 to 10,000 kDa [3]. HA has an unusual mechanism of biosynthesis and exceptional physical properties. Sodium hyaluronate is the predominant form of HA at physiological pH. Sodium hyaluronate and HA are collectively referred to as hyaluronan. Due to the fact that HA exists as a polyanion, it can self-associate and can also bind water molecules giving it a stiff, viscous quality with jelly-like consistency that causes it to behave like a lubricant [2].

HA was found to be abundantly distributed in cellular surfaces, in the basic extracellular substances of the connective tissues of vertebrates, in the synovial fluid of joints, in the vitreous humor of the eye, and in the tissue of the umbilical cord; all this attracted significant attention regarding its medical applications [4]. Although HA has a very simple structure, almost everything else concerning the molecule is unusual. Sometimes its role is mechanical and structural, such as in synovial fluid, the vitreous humor, or the umbilical cord. In other cases, it can interact in low concentrations with cells to trigger important cellular responses. HA's characteristics, including its consistency, biocompatibility, and hydrophilicity, have made it an excellent moisturizer in cosmetic dermatology and skin-care products. Moreover, its unique viscoelasticity and limited immunogenicity have led it to be used for viscosupplementation in osteoarthritis treatment, as a surgical aid in ophthalmology, and for surgical wound regeneration in dermatology. In addition, HA has currently been explored as a drug delivery agent for different routes such as nasal, pulmonary, ophthalmic, topical, and parenteral [2]. Hence the use of nanotechnology would combine the outstanding properties of HA being biocompatible, biodegradable, nontoxic, and able to bind specific receptors with the different advantages of nanoparticles such as enhanced therapeutic effects and targetability. In this chapter, the use of HA nanoparticles as a versatile drug delivery system will be discussed by highlighting the different production techniques based on the chemical and biological properties of HA.

2 Hyaluronic acid

2.1 Chemistry

The exact chemical structure of HA was determined by Weissman and Meyer in 1954. As already noted, HA belongs to a group of substances called mucopolysaccharides belonging to the GAGs family. It is an unbranched nonsulfated GAG composed of repeating disaccharides [β-1,4-d-glucuronic acid (known as uronic acid) and β-1,3-N-acetyl-d-glucosamide], as shown in Fig. 1.1. Both sugars are spatially related to glucose in the beta configuration, thus allowing all its bulky groups (the hydroxyls, the carboxylate moiety and the anomeric carbon on the adjacent sugar) to be in sterically favorable equatorial positions, while all the small hydrogen atoms occupy the less sterically favorable axial positions. Thus, the structure of the disaccharide is energetically very stable [3].

Fig. 1.1 Chemical structure of hyaluronic acid unit.

The HA backbone is stiffened in physiological solution via a combination of internal hydrogen bonds, interactions with solvents, and the chemical structure of the disaccharide. HA molecular investigations suggested that the axial hydrogen atoms form a nonpolar face (relatively hydrophobic) and the equatorial side chains form a more polar face (hydrophilic) which leads to a twisted ribbon structure for HA called a coiled structure [4].

Owing to this conformational behavior as well as its high molecular weight, the solutions of HA are very viscous and elastic. At very low concentrations, chains entangle with each other, leading to a mild viscosity (molecular weight dependent). However, HA solutions at higher concentrations have a higher than expected viscosity due to greater HA chain entanglement that is shear-dependent. For instance, a 1% solution of high molecular weight HA can behave like jelly, but when shear stress is applied, it will easily shear thinly and can be administered via a fine needle [2]. HA is therefore a “pseudo-plastic” material. This rheological property (concentration and molecular weight dependent) of HA solutions has made it ideal as a lubricant in biomedical applications. There is evidence that hyaluronan separates most tissue surfaces that slide along each other. The extremely lubricious properties of hyaluronan, meanwhile, have been shown to reduce postoperative adhesion formation following abdominal and orthopedic surgery.

HA has several interesting medical, pharmaceutical, food, and cosmetic uses in its naturally occurring linear form. However, chemical modifications of the HA structure represent a strategy to extend the possible applications of the polymer, obtaining better performing products that can satisfy specific demands and can be characterized by a longer half-life. During the design of novel synthetic derivatives, particular attention is paid to avoid the loss of native HA properties such as biocompatibility, biodegradability, and mucoadhesivity [5]. HA can be chemically modified by crosslinking or conjugation reactions. These chemical modifications mainly involve two functional sites of the biopolymer: the hydroxyl (probably the primary alcoholic function of the N-acetyl-d-glucosamine) and the carboxyl groups [6]. Furthermore, synthetic modifications can be performed after the deacetylation of HAN-acetyl groups [7].

Conjugation reactions usually consist of adding a monofunctional molecule onto one HA chain by a single covalent bond, while...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1: Versatile hyaluronic acid nanoparticles for improved drug delivery
• Chapter 2: Preclinical testing—Understanding the basics first
• Chapter 3: Aqueous polymeric coatings: New opportunities in drug delivery systems
• Chapter 4: Large-scale manufacturing of nanoparticles—An industrial outlook
• Chapter 5: The role of polymers and excipients in developing amorphous solid dispersions: An industrial perspective
• Chapter 6: Biologics: Delivery options and formulation strategies
• Chapter 7: Ethical issues in research and development of nanoparticles
• Chapter 8: Sterilization of pharmaceutical dosage forms
• Chapter 9: Vaccine delivery strategies against botulism
• Chapter 10: Nanotechnological approaches for delivery of antiinflammatory drugs
• Chapter 11: Food to medicine transformation of stilbenoid vesicular and lipid-based nanocarriers: Technological advances
• Index