Formulation, optimization, hemocompatibility and pharmacokinetic evaluation of PLGA nanoparticles containing paclitaxel

OBJECTIVE: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use. SIGNIFICANCE: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use. METHODS AND RESULTS: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2 nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box-Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5 ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation. CONCLUSION: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.