Encapsulation of drug into biopolymeric matrices based on modified xanthan gum and chitosan microparticles

Abstract

The drug delivery concept is defined as a method of routing a drug or an active compound to achieve a therapeutic effect in the living body. Past a few decades, the scope of drug delivery has been extended due to the improvement in nanotechnology. Nano or micro structures offer superior drug delivery systems (DDSs) for enhanced management and treatment of various diseases. Conventional approaches on drug delivery systems are losing their charm to smart and controlled DDSs which enable reducing applying dosage frequency, less systemic side effects and maintaining sufficient drug concentration in targeted organs. In order to improve the therapeutic effect of active molecules, DDSs are designed to guide them towards to selected region in the body without undesirable side effects. Many polymers have been tailored and used as drug carriers due enhance drug loading, control the drug release, and deliver the drug into the selected area in the body. Chitosan is a natural cationic polysaccharide obtained by deacetylation of chitin. Chitosan is receiving a lot of interest in the encapsulation of drugs and bioactive compounds due to its biocompatibility, low toxicity and biodegradability. The positive surface charge of chitosan makes it suitable for drug delivery and clinical applications. Crosslinking of chitosan can be delivered by both ionic and covalent cross-linkers. However, due to their toxicity, most chemical cross-linkers described in the literature, such as formaldehyde, glutaraldehyde, glyoxal, and epichlorohydrin, can cause problems in clinical usage. Xanthan gum (XG) is a negatively charged natural polymer that is produced from a gram-negative bacteria called Xanthomonas campestris via enzymatic biosynthesis. It can be classified as a microbial polysaccharide due to its resource. Important features of xanthan gum are non-toxicity, biocompatibility, remarkable viscosity and swelling properties. Due to its features, XG is widely used in drug delivery, tissue engineering and cosmetic applications. The anionic nature of XG makes it a good candidate for interacting with positively charged chitosan and forming polyelectrolyte complexes which are widely used in encapsulation or entrapment of natural active molecules such as essential oils. The aim of this study is to develop and optimize a safe encapsulation system for drug delivery in the human body. Trans-cinnamaldehyde (TC) is a natural active molecule extracted from cinnamon oil which is known for its antibacterial and antifungal activity. Like many phytochemicals, TC is also very vulnerable to losing its activity via degradation and volatilization. Encapsulation of TC provides a protection to this active molecule against enzymatic and pH-related degradations and also enhances its chemical stability. Encapsulation of trans-cinnamaldehyde with natural polymers and optimizing the release rate of active molecules of the system at different pH values can be used in controlling human pathogens in the gastrointestinal tract (GIT) without causing toxic effects. In this thesis, xanthan gum was modified by sodium periodate oxidation and dialdehyde xanthan gum (DXG) was obtained to use as a safe alternative crosslinker for chitosan. Sodium periodate oxidation is an effective method for introducing dialdehyde groups into the polymer backbone since the modification of xanthan gum. This modification involves converting glucopyranose units of xanthan gum to aldehyde and creating extra functional sites for covalent cross-linking. The oxidation procedure of xanthan gum is based on creating C-C cleavage between C2-C3 glucosidic bond by oxidizing hydroxy groups on them in the presence of sodium periodate (NaIO4). This generated cleavage then led to the formation of two aldehyde groups in each oxidized monomeric unit. Introduced aldehyde groups can react with amine groups of chitosan by Schiff base reaction and form imine bonds. Covalent cross-linking allows chitosan to release less active molecules in acidic pH such as gastric fluid and release more active molecules at neutral pH such as intestinal fluid where it is intended to use. In this thesis, dialdehyde xanthan gum was synthesized with an oxidization degree of 29.4 %. Microparticles were synthesized by changing the concentrations of DXG while keeping the concentration of chitosan constant and optimized in terms of size, encapsulation efficiency and loading capacity. Obtained microparticles were characterized by FTIR, DSC, SEM and DLS measurements. Release studies of trans-cinnamaldehyde loaded microparticles were investigated as a function of pH values in buffer solutions. Trans-cinnamaldehyde loaded dialdehyde xanthan gum-chitosan microparticles have been shown 80.06 % encapsulation efficiency, over 6.0 µm size with 0.310 PDI value. Loading of trans-cinnamaldehyde into synthesized microparticles has been proved via FTIR and DSC analysis. The surface roughness of particles has been demonstrated by SEM analysis. The release profile of synthesized microparticles indicated that the particles showed slower release in acidic conditions and faster release in neutral conditions, compared to its control groups.