Preparation and optimization of folic acid conjugated-chitosan functionalized PLGA nanoparticles for delivery of carboplatin

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

Carboplatin, a platinum-based antitumoral drug, represents a chemotherapeutic agent for newly diagnosed malignancies and it is effective for testicular, ovarian, bladder, head and neck cancers. However, low uptake of carboplatin by tumor cells is considered a key reason for its limited therapeutic efficacy [1]. 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, using TPGS (D-α-tocopheryl polyethylene glycol succinate) as stabilizer [2]. In order to improve the delivery of carboplatin to cancer cells, folic acid-conjugated chitosan-coated (FA-CS) PLGA nanoparticles were also prepared using experimental design [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 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. For surface modification, carboplatin-loaded PLGA nanoparticles suspension was mixed with FA-CS solutions in 1% acetic acid. For unmodified nanoparticles, the results showed that 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, with entrapment efficiency = 5% and nanoparticle yield = 77%. Also, it was possible to improve both parameters (EE = 37% and Yield = 87%) by reduction of dialysis (24 h to 2 h) and acetone evaporation (24 h to 1 h) time. Encapsulation of carboplatin was confirmed by UV-Vis spectroscopy using a derivatization technique with o-phenylenediamine. Mean particle size and polydispersity index are dependent of stirring time and concentration of FA-CS solution (according to a quadratic model), while zeta potential is also dependent but according to a linear model. REFERENCES – [1] S. Jose et al, Colloids and Surfaces B: Biointerfaces 142 (2016) 307-314. [2] O. S. Muddineti et al, Expert Opinion on Drug Delivery 14 (2017) 715-726. [3] J. Ji et al, Nanoscale Research Letters (2015) 10:453.