Investigation Of A Novel PECT Based Drug Delivery System Of IPF Loaded Amphiphilic Thermosensitive Hydrogel

Objectives To fabricate ibuprofen(IPF)-loaded a novel thermosensitive amphiphilic triblockcopolymer,poly(3-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)poly(ethyleneglycol)–poly(3-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)(PECT) using the nanometer precipitation technology. Its morphology observation, and its phase transition behavior, and to analyze its drug release characteristics;determination of in vitro cell biological safety and anti-inflammatory effect. Aimed at local slow-release preparation possesses characteristics, at the same time can have effective anti-inflammatory effect of gel to provide basic research.Methods 1. Through Scanning Electronic Microscope(SEM) and Transmission Electron microscopy(TEM), observing the PECT loaded of ibuprofen or not morphology under different condition;By adopting the method of small bottle flip the IPF/PECT water dispersion phase transition behavior;Determination of in vitro drug release curve. 2. Immunohistochemical method to identify the source of cells, grew well of 4 to 6 generation of HGFs used in the experiment.Different drug concentrations in vitro(IPF) based on PECT/PECT nanoparticles aqueous solution with HGFs training with methyl thiazolyl terazolium(MTT) in 48 h test of experimental group HGFs proliferation activity. 3. 1 ug/ml Pg- LPS PGE2 expression was significantly increased after the treatment HGFs, cell inflammation model was established successfully.ELISA method were used to detect inflammatory cells that PGE2 in supernatant fluid shows: IPF aqueous solution at different time points and IPF/PECT NPs anti-inflammatory effect than the control group.Results 1. Transmission electron microscopy(TEM) shows that: using the load of the preparation of nano precipitated ibuprofen nanoparticles(IPF/PECT NPs), made from producing frozen storage.IPF/PECT producing in double steaming water preparation of IPF/PECT NPs dispersion, under normal temperature for the solution, put a small bottle at 37 ? thermostat visible phase transition occurs in the solution for a minute.Scanning electron microscopy(SEM) showed that the IPF/PECT gel aperture size uniform, a no-load medicine gel pore size bigger, be helpful for drug release;drugs like linear release can reach more than 32 days, drug accumulation to release a quantity to 85%, no obvious interpretation of the phenomenon. 2. Determined by MTT method to detect the proliferation activity of HGFs: IPF/PECT and HGFs jointly develop different concentrations after 48 hours, the average each OD values were0.29±0.01 ? 0.28±0.01 ? 0.29±0.02 ? 0.29±0.03 ?0.29±0.03?0.29±0.03?0.28±0.02, the experimental group compared with the control group had no statistical significance(P? 0.05). 3. 1 ug/ml Pg- LPS PGE2 expression was significantly increased after the treatment HGFs, cell inflammation model was established successfully.ELISA method were used to detect inflammatory cells that PGE2 in supernatant fluid shows: IPF aqueous solution at different time points and IPF/PECT NPs anti-inflammatory effect than the control group;The same drug concentration of IPF/PECT NPs anti-inflammatory effect were better than the IPF aqueous solution, differences were statistically significant(P < 0.05).Conclusions 1. Precipitation using nanometer technology to the preparation of the load of ibuprofen new parents win min in situ gel.IPF and PECT quality than 5:10 0, drug-loading rate is optimal, morphological structure stability, sustained release effect is good. 2. Carrier for PECT after new slow-release drug had no effect on HGFs proliferation in vitro, has a good biocompatibility. 3. IPF/PECT at each time point compared with IPF anti-inflammatory effect, has obvious advantage, and with the extension of time, the anti-inflammatory effect of IPF/PECT group gradually strengthened.