Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs’ size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.

Protein-based nanoparticles (NPs) are attracting increasing attention as sustainable platforms for advanced biomedical applications. However, achieving high encapsulation efficiencies without compromising nanoparticle stability and biocompatibility remains a key challenge for these bio-based delivery systems. In this context, bovine serum albumin (BSA) NPs crosslinked with genipin were developed as green and biocompatible nanocarriers with tunable physicochemical properties. The synthesis conditions were systematically optimized by varying reaction time, temperature, and the BSA:genipin ratio, with 24 h at room temperature and a 10:1 ratio yielding the most suitable NPs in terms of formation and colloidal stability. The optimized BSA NPs were then used to encapsulate sertraline and 5-fluorouracil, achieving encapsulation efficiencies of 82% and 40%, respectively. These results highlight the ability of this nanoplatform to incorporate bioactive compounds with distinct physicochemical characteristics, with the sertraline-loaded NPs showing particularly high loading efficiency for an albumin-based system. In vitro assays performed on normal prostate epithelial cells (PNT-2) and prostate cancer cells (22Rv1) showed that the BSA NPs modulated drug-induced cytotoxicity relative to free drugs, indicating a formulation-dependent biological response. These findings highlight the potential of genipin-crosslinked BSA NPs as a versatile and sustainable platform for drug delivery in cancer therapy.