Application of Nanocarriers to Improve the Bioavailability of Poorly Water-Soluble Drugs

Abstract

ABSTRACT Over 40% of newly discovered chemical entities and nearly 90% of pipeline molecules exhibit poor aqueous solubility, posing a significant hurdle in modern biopharmaceutics. These Biopharmaceutics Classification System (BCS) Class II and IV molecules demonstrate suboptimal therapeutic efficacy due to poor dissolution rates, low systemic bioavailability, and high patient to-patient variability. Nanotechnology-based drug delivery platforms have emerged as a definitive solution to overcome these biopharmaceutical limitations. This review provides a comprehensive analysis of various nanocarrier architectures, including polymeric nanoparticles, solid lipid nanoparticles (SLNs), liposomes, nanoemulsions, and polymeric micelles, designed specifically to enhance the dissolution and absorption of hydrophobic therapeutics. We systematically evaluate the underlying physicochemical and biological mechanisms governing bioavailability enhancement, such as particle size reduction, amorphous state stabilization, lymphatic transport pathways, and prolonged gastrointestinal residence time. Furthermore, this paper highlights critical formulation variables, manufacturing methodologies, and scaling constraints while providing a deep critical assessment of current literature gaps, clinical translation challenges, and regulatory bottlenecks. By integrating technical insights across mechanical and chemical enhancement methods, this review establishes a comprehensive framework for design optimization of advanced nanomedicines.

KEYWORDS: Nanocarriers, Bioavailability Enhancement, Poorly Water Soluble Drugs, BCS Class II, Liposomes, Polymeric Nanoparticles, Dissolution Kinetics.