Polymeric Nanoparticles for Oral, Parenteral and Transdermal Drug Delivery: Design Principles, Performance Optimization, and Translational Challenges

Polymeric nanoparticles have emerged as versatile and efficient drug delivery platforms capable of addressing the limitations associated with conventional dosage forms across oral, parenteral, and transdermal routes of administration. Their nanoscale dimensions, structural flexibility, and tunable physicochemical properties enable enhanced drug solubility, protection from degradation, controlled release, and targeted delivery. This review provides a comprehensive analysis of polymeric nanoparticles, emphasizing formulation design principles, preparation techniques, and physicochemical characterization strategies that govern their biological performance. Route-specific optimization approaches are discussed in detail, highlighting how polymer composition, particle size, surface modification, and release behavior can be tailored to overcome physiological barriers unique to each route of administration. Furthermore, the review critically examines biological interactions, pharmacokinetic behavior, therapeutic applications, and safety considerations of polymeric nanoparticle-based systems. Special attention is given to regulatory, manufacturing, and scale-up challenges that currently hinder clinical translation. By integrating formulation science with translational perspectives, this review aims to provide a consolidated framework for the rational design and successful clinical advancement of polymeric nanoparticle-based drug delivery systems.