Chitosan-Based Microparticulate Systems to Enhance the Bioavailability of Natural Products: Mechanistic Insights and Pharmaceutical Applications

Chitosan-based microencapsulation systems are emerging as promising, biocompatible carriers designed to overcome major pharmacokinetic limitations of natural therapeutic agents. Many phytochemicals exhibit poor water solubility, rapid degradation, and low intestinal absorption. As a biodegradable and mucoadhesive biopolymer, chitosan offers distinct advantages by controlling drug release, protecting compounds from enzymatic breakdown, and enhancing passive absorption through the paracellular pathway. These properties make chitosan suitable for delivering diverse bioactive molecules, including alkaloids, phenolics, and botanical extracts. This review examines the fundamental mechanisms and therapeutic significance of chitosan-based microstructures (microspheres and microcapsules) for transporting natural compounds. Key formulation parameters—such as molecular weight, degree of cross-linking, and microparticle size—are evaluated for their impact on drug loading and release behavior. Evidence shows that chitosan microencapsulation enhances therapeutic outcomes in various applications, including cancer therapy, gastrointestinal disorders, orthopedic regeneration, and tissue repair. The review also discusses advanced strategies, including surface functionalization and hybrid composite systems, developed to further improve chitosan’s performance. Despite substantial progress, clinical translation remains hindered by variability in material quality and regulatory constraints. Addressing these challenges through standardized characterization methods and scalable manufacturing approaches is essential for advancing chitosan microcarriers into clinically viable platforms for natural product therapeutics.