Mechanistic Design and Engineering of Nanocarrier Systems for Targeted Drug Delivery: Fabrication Strategies and Therapeutic Applications

Abstract

Despite significant advances in technology and medical sciences, and substantial investment in drug discovery by the pharmaceutical industry, the clinical success of therapeutic agents for cancer and chronic diseases remains limited. Poor aqueous solubility, low bioavailability, rapid systemic clearance, and restricted access to target tissues continue to compromise therapeutic outcomes. Nanocarrier-based drug delivery systems have emerged as rationally engineered platforms capable of overcoming these limitations through controlled release, enhanced tissue accumulation, and improved pharmacokinetic profiles. This review provides a critical overview of recent developments in the mechanistic design, fabrication strategies, and therapeutic relevance of polymeric, lipid-based, inorganic, and hybrid nanocarriers for spatially and temporally controlled drug delivery. Particular emphasis is placed on understanding structure–function relationships that govern drug encapsulation, stability, safety, biological interactions, barrier penetration, and target specificity, including strategies to overcome the tumour microenvironment and the blood–brain barrier. Fundamental fabrication approaches such as nanoprecipitation, double emulsion techniques, surface functionalization, and stimuli-responsive systems are discussed in relation to therapeutic performance. Translational considerations including scale-up feasibility, regulatory challenges, and safety assessment are also addressed. Although substantial preclinical progress has been achieved, further standardization and integration of quality-by-design principles are essential to enable reliable clinical translation and precision therapeutics.