HSPiP Guided and QbD Optimization of Core-Shell Polymeric Nanoparticles for Enhancing the Delivery of Nutraceutical Bioactive Compound

Silymarin is an antioxidant compound with multiple proven pharmacological benefits, but it faces several obstacles that hinder its full efficacy, including poor solubility and bioavailability, as well as a short half-life. Therefore, encapsulating SM in core-shell polymeric nanocapsules can overcome those obstacles and control its release, thereby improving SM properties overall. The HSPIP computational screening approach is a sustainable and inexpensive alternative to the standard wet-lab screening method, which is exceedingly costly, time-consuming, and associated with significant chemical and solvent usage. In this study, the HSPIP computational screening method was used to calculate the solubility of SM in 13 different liquid lipids. QbD (quality by design) was further used to optimize formulation parameters, resulting in the optimized formula SM-PLGA-PNCs. SM-PLGA-PNCs resulted in particle size of 58.09 ± 0.79, zeta potential of 16.4 ± 1.3, PDI of 0.246 ± 0.001, and EE% 98.3±0.006. It was characterized by TEM, which revealed a morphology of uniformly sized spherical capsules, with no visible agglomerates. Additionally, FTIR was conducted to evaluate drug interactions and chemical properties, and showed compatibility between SM and the polymer, confirming the successful encapsulation of SM in SM-PLGA-PNCs. An XRD study was also conducted, confirming the FTIR results. Moreover, an in-vitro release study comparing the SM suspension and SM-PLGA-PNCs demonstrated the controlled-release effect of the optimized formula relative to the SM suspension.