Design and evaluation of biodegradable polymer-drug delivery systems

Thesis Abstract

The increasing demand for targeted, efficient, and biocompatible drug delivery systems has propelled research into biodegradable polymers as promising carriers for controlled therapeutic release. Despite significant advancements, challenges remain in optimizing polymer composition, drug-polymer interactions, and degradation profiles to enhance bioavailability and minimize adverse effects. This study aims to design, synthesize, and evaluate novel biodegradable polymer-drug delivery systems with improved performance for pharmaceutical applications. The specific objectives include synthesizing biodegradable polymers based on poly(lactic-co-glycolic acid) (PLGA) with tailored properties, immobilizing model drugs including doxycycline and insulin onto these carriers, and assessing their physicochemical, mechanical, and in vitro biological characteristics. The research adopts a mixed-methods approach, combining experimental synthesis and characterization with quantitative analysis of drug release profiles and biological efficacy. The study employs a design science research methodology to develop polymer formulations, integrating principles from the Theory of Polymer Degradation and Diffusion Models to inform scaffold design. The target population comprises laboratory-based synthesis and testing units, with a sample size of 30 distinct polymer formulations generated via a factorial design. Data collection instruments include Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and High-Performance Liquid Chromatography (HPLC). The validity and reliability of these instruments derive from calibration procedures, replicate analyses, and inter-operator assessments. Data analysis involves multivariate regression analysis to model drug release kinetics and ANOVA to compare performance across formulations. Additional analytical tools include kinetic modeling using zero-order, first-order, and Higuchi models, while degradation profiles are examined through weight loss measurements and morphological changes observed via SEM. The study hypothesizes that tailored polymer compositions will significantly influence drug encapsulation efficiency, release rate, and degradation behavior, with potential optimization achieved through iterative formulation adjustments. Expected findings indicate that specific copolymer ratios in PLGA can modulate the degradation time frame and achieve sustained drug release over periods of 14 to 30 days, with insulin-loaded systems demonstrating increased biocompatibility and stable release profiles. Comparisons between formulations are anticipated to reveal statistically significant differences (p < 0.05) in drug release kinetics, corroborated by regression models highlighting the influence of polymer hydrophilicity and molecular weight. The biological assessment predicts improved cellular compatibility and reduced inflammatory response in vitro, as evidenced by MTT cytotoxicity assays and cytokine profiling. This research contributes to existing knowledge by elucidating structure-property relationships in biodegradable polymer matrices and developing an optimized formulation platform for controlled drug delivery and tissue engineering applications. It advances theoretical understanding through the application of degradation/diffusion models and provides a practical framework for tailored carrier design. The main conclusion emphasizes the critical role of precise polymer synthesis parameters and drug-polymer interactions in achieving desirable release and degradation profiles. Recommendations include further in vivo validation of the optimized formulations, exploration of alternative biodegradable polymers such as polycaprolactone, and integration of stimuli-responsive elements for site-specific delivery. This study lays a foundation for translating laboratory findings into biomedical innovations that address current limitations in drug delivery systems, ultimately contributing toward personalized and sustainable therapeutic solutions.