Comparative Advances in Natural and Synthetic Polymer based Drug Delivery Systems for Diabetes Mellitus

Abstract

Background: Diabetes affects approximately 537 million people worldwide. As such, there is a growing need for treatment options that go beyond pharmacotherapy alone. Drug delivery systems (DDS) made from polymers have been developed to address some of the challenges commonly associated with drug delivery, including low bioavailability, inconsistent absorption rates, and high frequency of administration.

Objective: The purpose of this review is to compare natural polymers (i.e., chitosan, alginate, gelatin, hyaluronic acid, and dextran) to synthetic polymers (i.e., PLGA, PEG, PLA, PCL, and dendrimers) when used for insulin delivery, encapsulation of oral hypoglycaemic drugs, and glucose-responsive formulations.

Methods: The literature was searched using PubMed, Scopus, and Web of Science databases for articles published between 2010 and 2025, yielding numerous relevant articles.

Results: Natural polymers exhibit greater biocompatibility and mucoadhesion than synthetic polymers; however, they are limited by variability between batches and heterogeneity in structure. Conversely, synthetic polymers typically contain tunable degradation profiles and reproducibility as well as stimulusresponsiveness. Concerns associated with synthetic polymers include immunogenicity, and complexity of preparation. Hybrid formulations that contain both natural and synthetic polymers exhibit synergistic benefits and reduce the HbA1c by 1.4% to 2.5%.

Conclusion: Continued innovation in the development of smart, glucose-responsive, and personalised polymer-based DDS has the potential to revolutionise the treatment of diabetes. Additionally, regulatory alignment and strategies for scaling up manufacturing processes were identified as critical priorities.