Studies on nanogel drug delivery systems

It was aimed to develop and characterize nanogel drug delivery systems with various methods, loading of IL-2 to suitable formulations, in vitro evaluation of these IL-2 loaded formulations and to determine wound healing effect of selected IL-2 loaded nanogel formulation on insicision wounds in rats in this study.It was tried to prepare nanogel formulations using chitosan, dextran and natural polimer pullulan by chemical, high temperature application at acidic medium and ionic gelation methods respectively. Prepared nanogel formulations using last two method characterized by AFM, SEM, TEM, particle size, zeta potentials and suitable formulations were selected for further studies. IL-2 was then loaded to selected formulations. The loading capacity of nanogel formulations were determined using ELISA test. The release experiments from nanogel formulations were performed using Franz type diffusion cells and dialysis membrane with the pore size of 25000 Da at a medium of pH 7.4 phosphate buffer.Male Wistar rats were used for in vivo tests. The incision wounds were made and 300 µL of formulations were applied once a day with the dose of 500000 IU/mL. The wound healing effects of IL-2 loaded and unloaded nanogels were evaluated by determining the MDA (malondialdehyte), GSH (glutation) levels of wound tissues after 5th and 7th days.The most suitable artificial neural network modelling was developed using parameters for IL-2 free nanogel formulations (stirring rate, chitosan percentage, BSA percentage and TPP percentage as input parameters and particle size as output parameter).It was determined that prepared drug free chitosan-BSA nanogel formulations were more homogenous than that of chitosan-TPP formulations. Similarly, IL-2 loaded chitosan-BSA nanogel formulations were found to be more homogenous than that of chitosan-TPP formulations. Drug loading capacity was 100% for both chitosan-BSA and chitosan-TPP nanogels. Based on in vitro release studies, IL-2 release from nanogels was occured as rapidly at the beginning (burst effect) and slowly after second hour.Chitosan-TPP nanogels were not found to be very sticky after morphologic investigations and physical observations where as chitosan-BSA nanogels were quite sticky.IL-2 loaded chitosan-TPP nanogel formulations were found to be suitable for improving wound healing because they decreases the MDA levels and increases the GSH levels of wound tissues comparing to control group.All results showed that prepared chitosan-TPP nanogel can be effective for the treatment of wound healing.Keywords: Nanogels, Interleukin-2, chitosan-TPP nanogel, chitosan-BSA nanogel, wound healing, artificial neural network