Stimuli-responsive chitosan-based hydrogels for antibiotic delivery

Abstract

This study aims to investigate hydrogels fabricated via green approaches for drug delivery application. Biocompatible polymer-based drug delivery systems (DDS) have gained popularity in recent years because of their ability to improve the efficacy and safety of drug delivery by providing targeted and sustained release of drugs to reduce the frequency of dosing, making it more convenient for patients. Chitosan is one of the polymers commonly used for this purpose due to their higher water retention and porosity, which create space for loading medicine into the matrix. However, the potential utilization of endogenous and exogenous stimuli controlling drug release still remains challenging. Therefore, this research is focusing develop chitosan hydrogels used for targeted and controlled amoxicillin release. This study is divided into two main parts. Firstly, the fabrication and characterization of γ-irradiated chitosan (CS)/ polyvinyl alcohol (PVA) hydrogels were conducted to figure out the optimal ratio of CS and PVA under different gamma irradiation doses from 10 kGy to 30 kGy. At the ratio of CS/PVA of 50/50, the gel contents, thermal stabilities, mechanical strengths, and swelling degrees significantly increased as compared to those of the neat PVA and CS hydrogels at 25 kGy. Based on the protonate and de-protonate of amino groups on CS backbones in an acidic or basic environment, those γ-irradiated CS/PVA hydrogels were explored as pH-responsive drug carriers. The percentage release of amoxicillin (Amox) was estimated at 85 % and 50 % at pH 2.1 and 7.4 in PBS media. Meanwhile, the amount of Amox was around 34 % at pH 5.5 in DI water. Secondly, ultrasound (US) triggered DDS based on CS/EGDE hydrogel was investigated. The release of Amox from the hydrogel matrix was triggered by US under different US powers (0, 10, 20, and 35 W) at 43 kHz using CS solutions of concentrations ranging from 1.5 wt% to 3 wt%. The greater Amox release was observed in 2% CS compared to 1.5, 2.5, and 3 wt% because of drug-encapsulated effectiveness, crosslink density, and the effect of US on the polymer matrix. Viscoelasticity of CS/EGDE/Amox hydrogel with or without US was carried out to evaluate the softening effect of US on CS/EGDE/Amox hydrogel for lower CS content at 1.5 and 2 wt%, meanwhile at 2.5 or 3 wt% of CS remained unchanged G' value at 0.01 % strain. Moreover, the hydrogels at higher CS concentrations like 2.5 and 3 wt% became somewhat rigid after US irradiation for 120 mins. To study the Amox release mechanism, several models consisting of zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas were applied. It indicated that Amox release is mediated by a non-Fickian transport mechanism which means the release depended on both diffusion and swellable porous matrix.