Preparation and optimization of vitamin E TPGS-functionalized PLGA nanoparticles for carboplatin encapsulation

Carboplatin, a platinum-based antineoplasic drug, represents an excellent chemotherapeutic agent for newly diagnosed malignancies and it is effective for testicular, ovarian, bladder, head and neck cancers [1]. However, low... [ view full abstract ]

Carboplatin, a platinum-based antineoplasic drug, represents an excellent chemotherapeutic agent for newly diagnosed malignancies and it is effective for testicular, ovarian, bladder, head and neck cancers [1]. However, low uptake of carboplatin by tumor cells is considered a key reason for its limited therapeutic efficacy [2]. In this work nanoparticles composed of poly(D-L-lactic-co-glycolic) acid (PLGA) were prepared to produce nanocarriers for carboplatin. The carboplatin loaded PLGA nanoparticles were formulated by nanoprecipitation method and experimental design, using TPGS (D-α-tocopheryl polyethylene glycol succinate) as stabilizer [3]. Briefly, PLGA was dissolved in acetone while an aqueous solution of carboplatin was prepared. Drug solution was added to the PLGA solution and the biphasic mixture was sonicated to give a primary w/o emulsion. This emulsified mixture was added to a solution containing TPGS and sonicated again to give a double emulsion (w/o/w). Following evaporation of acetone, a suspension of NPs was obtained and purified by ultracentrifugation (20,000 rpm for 15 min and 2 washes with distilled water) or dialysis (membrane with 3500 Da MWCO for 24 h). The results showed that average hydrodynamic diameter is dependent of time, amplitude of sonication, volume and concentration of TPGS aqueous solution (according to a linear model), while polydispersity index and zeta potential are constants (0.10-0.30 and -30 mV). Encapsulation of carboplatin was confirmed by UV-Vis spectroscopy using a derivatization technique with o-phenylenediamine. Dialysis was chosen as purification method because higher values were obtained for entrapment efficiency (5%) and nanoparticle yield (77%) in comparison to ultracentrifugation. Moreover, the optimized formulation (mean particle size = 121.0 nm, PDI = 0.120 and zeta potential = -34.0 mV) was stable over a period of 60 days when stored at 10°C. REFERENCES - [1] S. Jose et al, Colloids and Surfaces B: Biointerfaces 142 (2016) 307-314. [2] T. Sadhukha and S. Prabha, AAPS PharmSciTech 15 (2014) 1029-1038. [3] N. A. Peppas et al, Journal of Controlled Release 190 (2014) 29-74.