Rational Design of Biodegradable Polymeric Nanoparticles: From Formulation Parameters to Particle Properties
Biodegradable polymer nanoparticles have transformed the landscape of nanotherapeutics, enabling the clinical translation of numerous delivery platforms. Yet, persistent challenges - including low drug loading, premature cargo release and variable therapeutic performance - continue to limit clinical efficacy.[1] In this regard, we systematically investigated how process parameters and formulation variables govern the structural characteristics of such assemblies. Specifically, we evaluate the influence of the formulation strategy (film hydration, solvent switch, and nanoprecipitation), polymer chemistry and concentration, solvent composition, dispersion medium, and organic-to-aqueous phase ratio (OAPR) on nanoparticle size, size distribution, and surface charge. Using poly(ethylene oxide)-b-poly(lactic acid) (PEO-b-PLA) and poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL), nanoparticles were prepared by the three approaches and characterized by scattering and imaging. Formulation strategy emerged as a determinant factor on nanoparticle size. Film hydration produced the largest particles (PEO-b-PLA, 454 nm), whereas nanoprecipitation yielded the smallest (PEO-b-PCL, 26 nm). We further show that modulating solvent selection and mixtures, precise and linear tuning of nanoparticle size within the sub-100 nm range could be reached. These findings provide a rational framework for engineering robust nanocarriers with tunable dimensions.