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

Abstract

Over 40% of newly discovered chemical entities and nearly 90% of pipelinemolecules exhibit poor aqueous solubility, posing a significant hurdle inmodern 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 biopharmaceuticallimitations. This review provides a comprehensive analysis of variousnanocarrier architectures, including polymeric nanoparticles, solid lipidnanoparticles (SLNs), liposomes, nanoemulsions, and polymeric micelles,designed specifically to enhance the dissolution and absorption of hydrophobic therapeutics. We systematically evaluate the underlyingphysicochemical and biological mechanisms governing bioavailabilityenhancement, 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 advancednanomedicines.  KEYWORDS: Nanocarriers, Bioavailability Enhancement, Poorly Water-Soluble Drugs, BCS Class II, Liposomes, Polymeric Nanoparticles,Dissolution Kinetics.