Amine-functionalized poly(lactic-co-glycolic acid) nanoparticles for improved cellular uptake and tumor penetration

Amine-functionalized poly(lactic-co-glycolic acid) (PLGA-NH₂) nanoparticles (NPs) were developed for the delivery of phloretin. PLGA-NH₂/phloretin NPs with 237nm mean diameter, narrow size distribution, and around -6mV zeta potential were fabricated by a modified emulsification-solvent evaporation method. The results of solid state studies revealed that drug was successfully incorporated into the polymeric NPs. The initial particle size of developed NPs was maintained after 24h incubation in human serum albumin (HSA) solution, fetal bovine serum (FBS), and phosphate buffered saline (PBS). Sustained and higher drug release patterns at acidic pH (pH 5.5), compared with neutral pH (pH 7.4), from PLGA-NH₂ NPs were observed. The experimental data of flow cytometry and confocal laser scanning microscopy (CLSM) studies suggested that PLGA-NH₂ NPs may have an improved cellular accumulation efficiency, compared with PLGA NPs, in Hep-2 cells (human laryngeal carcinoma). Also, PLGA-NH₂ NPs exhibited enhanced growth inhibitory effects rather than PLGA NPs in Hep-2 spheroid model. By introducing a simple strategy based on amine-functionalization of PLGA NPs (without installing complicated functional moieties), improved cellular uptake and antitumor efficacies without severe toxicity, compared with unmodified PLGA NPs, have been accomplished.