Applications of Nanocomposite Materials in Drug Delivery

Inamuddin, Abdullah M. Asiri, Ali Mohammad, Dr. Inamuddin

• Publisher: Woodhead Publishing
• Year: 2018
• Print ISBN:
  9780128137413
• eBook ISBN:
  9780128137581
• Topic: Technology & Engineering
• Subtopic: Chemical & Biochemical Engineering
• Index: Technology & Engineering

Applications of Nanocomposite in Drug Delivery discusses and explores the applications of nanocomposites in the area of drug delivery. Starting with a scientific understanding of drug delivery fundamentals, the book explores the utility of nanocomposites in the area of controlled, transdermal, osteo-articular tuberculosis and stimulus sensitive drug delivery applications. The book intricately details and discusses a variety of methods for their preparation, while also highlighting specific applications of nanocomposites in targeted drug delivery. - Discusses nanocomposite and nanotechnology for drug delivery - Outlines the mechanisms involved in targeted drug delivery using nanocomposites - Includes synthesis methods for nanocomposites used in controlled drug delivery - Lists various applications of nanocomposites in drug delivery

1

Chitosan-based nanocomposites for drug delivery

Patrícia H. Yassue-Cordeiro¹, Patrícia Severino², Eliana B. Souto³, Eliezer L. Gomes⁴, Cristiana M.P. Yoshida⁴, Mariana A. de Moraes⁴ and Classius F. da Silva⁴, ¹Departamento de Engenharia Química, Universidade Estadual de Maringá, Maringá, Brazil, ²Instituto de Tecnologia e Pesquisa, Universidade Tiradentes, Aracaju, Brazil, ³Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal, ⁴Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brazil

Abstract

Chitosan (CS) is a semi-synthetic biopolymer obtained from chitin that is the second most abundant biopolymer. Many devices produced from CS have been widely used for drug delivery systems and biomaterials. Biocompatibility, biodegradability, nonallergenicity, and antimicrobial activity are advantageous properties of CS; moreover, CS has also exhibited healing properties. Some properties can be potentiated by using the CS to produce CS-based nanocomposites. In this sense, this chapter intends to give some CS nanodevices with different kind of fillers (reinforcements) and their application to the drug delivery systems. Fillers such as nanoparticles, nanolayer, and nanofibrous are discussed.

Keywords

Chitosan; chitosan-based nanocomposites; drug delivery systems; biomaterials; nanocomposite particles; nanocomposites films; nanocomposites scaffolds

1.1 Introduction

This chapter is divided into six sections. This first section is the Introduction to the addressed topics in this chapter. The second section presents some statistical data of publications concerning nanocomposites, drug delivery, and chitosan (CS). The third section summarizes some general concepts about CS and its chemical, physical, and biological properties. The fourth section illustrates the overview aspects to produce some CS devices such as particles, films, and scaffolds that can be used as a matrix to the nanocomposites. The fifth section presents the filler materials that can be used to prepare CS-based nanocomposites for drug delivery; this section has been divided into three sub-sections, where the fillers were classified as nanoparticles (NPs), nanofibrous, and nanolayers. The last and sixth section is the conclusion providing the summary of CS-based nanocomposite for drug delivery systems.

1.2 An overview of papers about chitosan-based nanocomposite for drug delivery

The number of academic papers about nanocomposites has increased significantly in recent years. Fig. 1.1A shows the number of scientific articles resulting out from searches conducted on the Scopus (www.scopus.com) that is the most outstanding abstract and citation database of peer-reviewed literature. The search field chosen to obtain the data were article title, abstract, and keywords. We restricted the search to the scientific journals and conference proceedings published in the English language during the last 15 years, covering the period 2002–2016. Moreover, we improved our search by using “*” as a wildcard to find plural and inflected forms of words; then the first search was Nanocomposite* which could be “Nanocomposite” or “Nanocomposites.” During the last 15 years, the number of papers jumped from 1169 in 2002 to 12,670 in 2016, that is an increase of more than 10 times (Fig. 1.1A). The total papers appeared were 103,378. By refining the search, it was included another term to the search field that was “Drug Delivery.” This search presented the same tendency, and the numbers jumped from 3 in 2002 to 247 in 2016, that represents an increase of more than 80 times. On the other hand, the total number of papers in this refining search was about 2% of the whole papers about nanocomposites.

Figure 1.1 Academic papers published per year according to Scopus database: (A) general search, (B) refined search.

Fig. 1.1B shows the last search that was refined to Nanocomposite* AND “drug delivery” AND “Chit*.” The term “Chit*” could find even “chitosan” and “chitin,” as the definition of chitin and CS depends on the authors, we decided to include both. The number of papers was null between 2002 and 2006; the first papers was just found in 2002. Moreover, the tendency of the number of papers has increased between 2006 and 2016 being the last year the maximum, 40 papers. It is important to mention that China, India, and United States, together, have more than half of the papers for the first (Nanocomposite*) and second search (Nanocomposite* AND “drug delivery”). On the other hand, when the term Chit* was added, Iran comes to the third position and United States becomes the sixth.

1.3 Chitosan

CS is a biopolymer derived from chitin by partial deacetylation of acetyl groups in alkaline media. Fig. 1.2 shows that CS is a copolymer that has two units: (1) β-(1-4)-2-acetoamido-D-glucose (also named N-acetyl-D-glucosamine or GlcNAc), (2) and β-(1-4)-2-amino-D-glucose (also named D-glucosamine or GlcN). The term “chitosan” is usually employed when the GlcN units are more than 60%. The glucosamine and N-acetyl-glucosamine monomers are randomly distributed. The degree of acetylation and molar mass are two fundamental parameters that can affect the properties and functionality of CS. These properties include solubility, viscosity, the reactivity of proteinaceous material, coagulation, and heavy metal ion chelation [1]. CS can dissolve in dilute acids such as acetic acid, formic acid, and others. The solubilization occurs by protonation of the NH₂ functional group to ${\mathrm{NH}}_3^{+}$

, and the cationic CS molecule interacts with negatively charged surfaces that modify its physicochemical characteristics [2].

Figure 1.2 Symbolic reaction of chitin deacetylation to produce chitosan.

1.3.1 Chemical and physical properties of chitosan

CS is characterized by excellent chemical and biological properties that can be used in a wide range of applications, such as food, cosmetics, water treatment, membranes, environmental protection, materials development, biomedicine, tissue engineering, and others. The biocompatibility, biodegradability, nonallergenicity, film forming capacity, and antibacterial activity are advantageous properties of CS [3,4].

In the solid state, CS is semi-crystalline polymer presenting different crystalline polymorphic forms [5]. It is characterized by an extended twofold helical structure, differing in packing density and water content. The hydrated “tendon” CS can be quite easily converted into the anhydrous crystalline form by annealing [6] or transformation by CS/monocarboxylic salt [7].

Apart from amino groups, CS has two hydroxyl groups for appropriate chemical modifications. CS could undergo different reactions such as etherification, esterification, and cross-linking [8]. CS forms water-soluble salts with inorganic and organic acids [9] and it has a strong affinity to bind with metal ions. Immersing a tendon CS in various metal salt solutions such as Cd²⁺, Cr³⁺, Hg²⁺, Pb²⁺, Zn²⁺, or Cu²⁺ ions give X-ray diffraction patterns where the primary amino group is one of the ligands [10]. The intrinsic pKa value of CS depends on the degree of acetylation, ionic strength, and the charge neutralization of –NH₂ groups [11].

1.3.2 Biological properties of chitosan

CS and derivatives with higher antimicrobial activities have been synthesized [12]. The CS blended with nylon-6 chelated with silver ions presented antibacterial properties against Gram-positive and Gram-negative bacteria [13]. Devlieghere et al. [14] quantified the antimicrobial effect of a commercial CS with high deacetylation degree (94%) and low molar mass on different psychrotrophic spoilage organisms and food pathogens. They concluded that Gram-negative bacteria were very susceptible to the applied CS while the sensitivity of Gram-positive was highly variable. CS -zinc complexes showed a broad spectrum of effective antimicrobial activities and had better antibacterial activity than antifungal activity [15]. Silva et al. [16] incorporated buriti oil in CS films and observed total microorganism barrier.

The antimicrobial activity of CS films and coatings were evaluated, noting that a quaternized CS, carboxymethyl CS, and quaternized carboxymethyl CS showed effective antimicrobial activities against to Escherichia coli and Staphylococcus aureus [17]. Seyfarth et al. [18] studied the antifungal activity of CS against Candida albicans, Candida krusei, and Candida glabrata. The first two were the most sensitive species. They concluded that antifungal activity was decreased with declining molar mass.

The wound healing process is another outstanding property of CS. Ueno et al. [19] studied the use of CS as an accelerator of wound healing in dogs. They suggested that CS can accelerate the infusion of polymorphonuclear cells (PMN) at the early stage of wound healing and increase the production of collagen by fibroblasts.

Howling et al. [20] demonstrated in vitro that CS has stimulatory effects on fibroblast pr...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of contributors
• Preface
• 1. Chitosan-based nanocomposites for drug delivery
• 2. Chitosan based nanocomposites for drug, gene delivery, and bioimaging applications
• 3. Alginate-inorganic composite particles as sustained drug delivery matrices
• 4. Applications of cellulose nanofibrils in drug delivery
• 5. Cyclodextrin-based nanosponges in drug delivery and cancer therapeutics: New perspectives for old problems
• 6. Development of injectable in situ gelling systems of doxycycline hyclate for controlled drug delivery system
• 7. Avidin-based nanoparticles for drug delivery
• 8. Carbon-based polymers for drug delivery
• 9. Carbon nanotube for targeted drug delivery
• 10. Polymer nanoparticle carriers in drug delivery systems: Research trend
• 11. Drug nanocrystals: Present, past and future
• 12. Drug delivery: Present, past, and future of medicine
• 13. Drug delivery for cardiac regeneration
• 14. Nanocomposite for cancer targeted drug delivery
• 15. Applications of nanocomposite materials in the delivery of anticancer drugs
• 16. Nanocomposite for transdermal drug delivery
• 17. Nanocomposites for therapeutic application in multiple sclerosis
• 18. Oral colon cancer targeting by chitosan nanocomposites
• 19. Potential of nanoparticles as drug delivery system for cancer treatment
• 20. Vesicular nanostructures for transdermal delivery
• 21. Nanoelectrospun matrices for localized drug delivery
• 22. Electrospun nanofiber scaffolds: Technology and applications
• 23. Hydrogel nanocomposite for controlled drug release
• 24. Mesoporous nanomaterials as carriers in drug delivery
• 25. Metal organic frameworks for drug delivery
• 26. Microwave synthesized nanocomposites for enhancing oral bioavailability of drugs
• 27. Montmorillonite clay nanocomposites for drug delivery
• 28. Nanocomposite microemulsions study of single-walled carbon nanotubes in arteries: Applications of nanocomposite materials in drug delivery
• 29. Nanoemulsion in drug delivery
• 30. Nanocomposite scaffolds for tissue engineering; properties, preparation and applications
• 31. Metal–ferrite nanocomposites for targeted drug delivery
• 32. Okra gum–alginate composites for controlled releasing drug delivery
• 33. Phase transition microemulsions as drug delivery systems
• 34. Polymer–ceramic nanocomposites for controlled drug delivery
• 35. Stimuli-responsive nanocomposites for drug delivery
• 36. Superparamagnetic nanoparticles for drug delivery
• 37. Superparamagnetic iron oxide nanoparticles for drug delivery
• Index