Study of the Copolymer Structure Effect on Physicochemical Characteristics and In Vitro Stability of PLGA- PEG Nanoparticles Loaded 9-Nitrocamptothecin

9-nitrocamptothecin (9-NC) is a semisynthetic and a low soluble analogue of camptothecin alkaloids that target nuclear enzyme topoisomerase I. The unsTable lactone form of 9-NC in biological fluids requires for its cytotoxic activity. To improve aqueous solubility and stability in biological media, 9-NC was loaded in polymeric nanoparticles. In this paper, we studied the effect of PEG percent (0, 5, 10, 15) in PLGA-PEG copolymer on physicochemical properties of nanocarriers. To acquire an optimum formulation, a Generalized Regression Neural Networks (GRNN) and a Multi-Layer Perceptron (MLP) as potent statistical methods were employed. The drug loaded parameters were the input vectors of the GRNN and included the amount of polymer and emulsifier, volume of external and internal phases. The nanoparticles drug loading constitutes the output vector of each network. In this way, GRNN and MLP are trained to investigate the functional influence of input variables on the output response.PLGA-PEG nanoparticles were prepared by nanopercipitation method. Zeta sizer, DSC, SEM and frantz diffusion cell were used to measure physicochemical properties of optimized formulations.The physicochemical properties of 9-NC nanoparticles influenced by PEG percent in PLGA-PEG copolymer. Drug loading increased which can be attributed to the hydrophobic nature of drug and amphiphilic nature of copolymer. The size of nanoparticle decreased by increasing the PEG percent in copolymer which can be attributed to emulsifing nature of PEG percent. Release rate decreased by increasing the percent of PEG in PLGA-PEG nanoparticles but in vitro stability increased. DSC thermograms and FT-IR results showed that 9-NC was encapsulated in PLGA-PEG nanoparticles in its amorphous form.According to artificial neural network (ANN) data, we found that PLGA-PEG (15%) had best physicochemical characteristic compare to other copolymer. The optimum formulation showed that these nanoparticles could be hopeful and potential carriers for delivery of unsTable and low soluble drugs especially anticancer agents.