Modified nanoprecipitation method for preparation of cytarabine-loaded PLGA nanoparticles

The present investigation was aimed at developing cytarabine-loaded poly(lactide-coglycolide) (PLGA)-based biodegradable nanoparticles by a modified nanoprecipitation which would have sustained release of the drug. Nine batches were prepared as per 3(2) factorial design to optimize volume of the co-solvent (0.22-0.37 ml) and volume of non-solvent (1.7-3.0 ml). A second 3(2) factorial design was used for optimization of drug: polymer ratio (1:5) and stirring time (30 min) based on the two responses, mean particle size (125 ± 2.5 nm), and percentage entrapment efficiency (21.8 ± 2.0%) of the Cyt-PLGA nanoparticles. Optimized formulation showed a zeta potential of -29.7 mV indicating good stability; 50% w/w of sucrose in Cyt-PLGA NP was added successfully as cryoprotectant during lyophilization for freeze-dried NPs and showed good dispersibility with minimum increase in their mean particle sizes. The DSC thermograms concluded that in the prepared PLGA NP, the drug was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. In vitro drug release from the pure drug was complete within 2 h, but was sustained up to 24 h from PLGA nanoparticles with Fickian diffusion. Stability studies showed that the developed PLGA NPs should be stored in the freeze-dried state at 2-8°C where they would remain stable in terms of both mean particle size and drug content for 2 months.