Analysis of drug release models from biodegradable nanomodified chitosan based materials

Abstract

Background: The problem of drug delivery to the tissue-damaged area of the human body remains relevant. Hydroxyapatite (HA), as one of the best known calcium phosphate (CaP) compounds, is used as an inorganic component of composite materials for drug loading. The organic components in composite materials are biopolymers such as alginate, agarose, chitosan (CS), collagen, and gelatin. Selected C60 nanoparticles are widely used as antibacterial agents and can strengthen the structure of composites. Microwave (MW) irradiation is an exposure method that shortens the synthesis time by significantly increasing the number of nucleation centers, which results the reducing the size of the crystallites formed, which affects the adsorption capacity of the product. Objectives: Most forms of drug delivery systems demonstrate rapid release of ceftriaxone (CFT) and anasthesin (ANA) within 2 days, characterized by a "burst release" that may cause overdose in the first hours of use. The aim of this work was to investigate and compare the drug release kinetics from convectionally and MW-synthesized CS matrices modified with HA, multiphasic CaP, and fullerene C60 nanoparticles for long-term bone tissue regeneration. Materials and methods: The study was performed by high-performance liquid chromatography (HPLC) using an Agilent 1200 device with a DAD detector (λ = 210–270 nm) and a C18 chromatographic column (Zorbax SB-C18 4.6×150 mm, 5 μm) at ambient temperature. Results: HA is a good adsorbent, but a poorly soluble substance, so the pharmacokinetics of ANA release was mainly determined by the degree of adsorption of the drug on the surface of the material and its diffusion potential. CS and C60 in the composition provide a prolonged release of ANA for up to 18 days. The release of CFT from CaP/CS matrices depends on the method of its introduction into the composite - during synthesis or saturation after synthesis. The saturation method is characterized by a fast release range of 24–48 hours, and adding during synthesis delays active release to 48–72 hours (start of degradation). The release index took values from n = 0.56 to n = 0.92, which corresponds to the release kinetics that does not follow Fick's law, and close to the first-order release kinetics model. Conclusions: Synthesized composites based on a CS matrix modified with nanostructured CaP particles and fullerene C60 are potential carriers of CFT and ANA with the function of their long-term release in areas of bone tissue injury.

Keywords

• chitosan
• hydroxyapatite
• fullerene c60
• drug release
• nanoparticles