Advancements in application of chitosan and cyclodextrins in biomedicine and pharmaceutics: recent progress and future trends

Abstract

The global community is faced with numerous health concerns such as cancer, cardiovascular and neurological diseases, diabetes, joint pain, osteoporosis, among others. With the advancement of research in the fields of materials chemistry and medicine, pharmaceutical technology and biomedical analysis have entered a new stage of development. The utilization of natural oligosaccharides and polysaccharides in pharmaceutical/biomedical studies has gained significant attention. Over the past decade, several studies have shown that chitosan and cyclodextrin have promising biomedical implications in background analysis, ongoing development, and critical applications in biomedical and pharmaceutical research fields. This review introduces different types of saccharides/natural biopolymers such as chitosan and cyclodextrin and discusses their wide-ranging applications in the biomedical/pharmaceutical research area. Recent research advances in pharmaceutics and drug delivery based on cyclodextrin, and their response to smart stimuli, as well as the biological functions of cyclodextrin and chitosan, such as the immunomodulatory effects, antioxidant, and antibacterial properties, have also been discussed, along with their applications in tissue engineering, wound dressing, and drug delivery systems. Finally, the innovative applications of chitosan and cyclodextrin in the pharmaceutical/biomedicine were reviewed, and current challenges, research/technological gaps, and future development opportunities were surveyed.

Introduction

Oligosaccharides and polysaccharides are a diverse group of natural polymers with important biological functions.1 The highest class of functional oligosaccharides are considered carbohydrates, whose monosaccharide units are fructose, galactose, glucose and/or xylose.2 These molecules are called prebiotics because they promote the growth of beneficial bacteria, especially Bifidobacterium species. These beneficial oligosaccharides have physical and physiological benefits that help improve consumers’ health. In this way, the application of oligosaccharides as additives in beneficial nutraceuticals has great potential to make major advances in the quality of nutraceuticals affecting the user’s health.

Functional oligosaccharides offer various health benefits and can be used as nutrients, medicine, animal feed, beauty products, immune-stimulating, and prebiotics.3,4 In expansion, known functional oligosaccharides incorporate arabinose–oligosaccharides, arabinogalactan–oligosaccharides, arabinoxylo–oligosaccharides, galacturonic–oligosaccharides and human draining oligosaccharides (HMOs). In particular, cyclodextrins, made from starch with modifications in the product, are a class of macrocyclic oligosaccharides.5,6 Cyclodextrins are cyclic α-(1/4)-glucans that polymerize levels of 6, 7, and 8 monosaccharide units, respectively. Macrocyclic carbohydrates are widely associated with supramolecular chemistry products, drug carriers, atomic reactors, and artificial devices.7 Since the 1950s, cyclodextrins have been recognized for their physicochemical properties and potential to enhance the solubility, stability, and bioavailability of molecular therapies. They can serve as multi-functional drug carriers through the formation of inclusion complexes or CyD/drug conjugates, making them attractive for drug delivery applications. The unique biocompatibility and functional capabilities of cyclodextrins and their derivatives have led to their development for biomedical materials. Beneficial oligosaccharides have been shown to promote intestinal regeneration and reduce8 the risk of intestinal diseases, obesity, cancer, body weight, and type 2 diabetes. As a result, they are recommended as important nutrients for metabolic diseases.9

Polysaccharides have various functional groups including hydroxyl, amino, carboxylate, sulfate and ester groups. Certain polysaccharides and their derivatives, such as alginate, starch, and particularly chitosan, exhibit mucosal adhesion properties due to modifications in hydrogen bonding, electrostatic attraction, and hydrophobic interactions.10

Polysaccharides like cellulose, xylan, and chitosan are structural components of plant cell walls and the shells of fish and reptiles. Other polysaccharides like glycogen, amylose, and amylopectin are important for sugar storage in bacteria and plants.11 Chitosan has attracted major scientific and industrial interests since the late 1970s. Because of its particular macromolecular structure, biocompatibility, biodegradability and other intrinsic functional properties, chitosan and its derivatives have practical applications in pharmacy, medicine, and chemistry.25 There has been notable advancement in understanding how certain compounds are synthesized in living organisms.12 This understanding has helped in discovering new types of sugars by exploring genetic information and has opened up possibilities to modify these sugars in a way that improves their medicinal properties.13 Many polysaccharides have anticancer activity.14

Usually, the way it works is by making the macrophages in the host become active.15 Sugar-based carbohydrates, which are used in biomedical applications to improve the ratio, are also used in unconventional applications.16 In biomedical applications, PEG (polyethylene glycol) is known as a safe and consistent material that can enhance the relaxation of some paramagnetic substances such as gadolinium diethylenetriaminepentacetate (Gd-DTPA) or ferrite.17 However, researchers have studied how saccharides affect T1 and T2 relativities as possible options.18 Polysaccharides like heparin, pullulan, and chitosan are used to target tumor cells.19 Small sugars can be used as a source of energy in living organisms.

These small sugars can be broken down easily and quickly to provide fuel for cells. Additionally, glycan is now being used in nanotechnology to prepare materials for purposes such as tissue engineering, drug delivery, inhibiting enzymes, and creating biosensors.16,20–22 The one important use the carbohydrates in medical science is their ability to be recognized and taken into cells by lectins on the surface of mammalian cells. Also having multiple valence or charge states is a common characteristic of transition metal elements.23 Scientists discovered that when multiple patterns of a substance join together on a specific target, it can increase the attachment strength between carbohydrates and protein receptors, this is called a multivalent ligand.24

This study aimed to explore the use of oligosaccharides derived from natural sources and bioactive polysaccharides. The review introduced various types of saccharides, defined natural biopolymers such as cyclodextrin and chitosan, and discussed their wide applications in biomedical fields that have received attention from researchers. Recent research advances in pharmaceutics, especially in drug delivery based on the response of cyclodextrin to smart stimuli, were also discussed. The review covered the biological functions of cyclodextrin and chitosan, including their antimicrobial, anti-oxidative, and immunomodulatory effects, as well as their applications in tissue engineering, wound dressing, and drug delivery systems. Innovative applications of saccharides were investigated. Finally, current challenges and future development opportunities were discussed. To aid in understanding the procedure, a summary is provided in Fig. 1.

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Farnaz Bahavarniaa, Mohammad Hasanzadeh, Parinaz Bahavarniac and Nasrin Shadjou, Advancements in application of chitosan and cyclodextrins in biomedicine and pharmaceutics: recent progress and future trends, RSC Adv., 2024, 14, 13384.

Read also our introduction article on Chitosan here:

Video: Chitosan as a natural excipient