Formulation of functionalized PLGA nanoparticles with folic acid-conjugated chitosan for carboplatin encapsulation

Abstract

Poly(d,l-lactic-co-glycolic acid), or PLGA, is the most frequently used biodegradable and biocompatible polymer in preparation of nanoparticles for biomedical applications. In this work nanoparticles composed of PLGA were prepared to produce nanocarriers for a platinum-based antitumoral drug: carboplatin. The carboplatin-loaded PLGA nanoparticles were obtained by nanoprecipitation method, using TPGS (D-α-tocopheryl polyethylene glycol succinate) as stabilizer and acetone as organic phase. In order to improve the delivery of carboplatin to cancer cells, folic acid-conjugated chitosan-coated (FA-CS) PLGA nanoparticles were also prepared, using 22 factorial design with center point for unmodified and surface modified nanoparticles. For PLGA nanoparticles, the results showed that mean particle size is dependent of time, amplitude of sonication, volume and concentration of TPGS aqueous solution (according to a linear model), while PDI and zeta potential are constants. The optimized formulation (121.0 nm, PDI = 0.120 and −34.0 mV) was stable over a period of 60 days when stored at 10 °C, with entrapment efficiency (EE) = 5%, drug loading = 0.37% and nanoparticle yield = 77%. Also, it was possible to improve these parameters (EE = 39.5%, drug loading = 2.6% and yield = 91%) by reduction of dialysis (24–2 h) and acetone evaporation (24–1 h) time. For surface modified PLGA nanoparticles, mean particle size and PDI are dependent of stirring time and concentration of FA-CS solution (according to a quadratic model), while zeta potential is also dependent of these factors but according to a linear model. The optimal formulation showed particles with size of 178.0 nm, PDI = 0.20, zeta potential = 46.0 mV, EE = 35.5%, drug loading = 1.8% and nanoparticle yield = 92%. Encapsulation of carboplatin was confirmed by UV–Vis spectroscopy using a derivatization technique with orto-phenylenediamine. In conclusion, the results obtained in this work demonstrated that formulation variables can be explored to obtain the optimal preparation conditions of PLGA nanoparticles.