Study On Chitosan And Chondroitin Sulfate Polyelectrolyte Nanoparticles

In this paper, preparation of chitosan chondroitin sulfate polyelectrolyte nanoparticles materials using chitosan and chondroitin sulfate, using baicalin as model drug to study on the application of the polyelectrolyte nanoparticles in drug delivery system. Baicalin is a kind of flavonoids, has extensive pharmacological effects, insoluble in water, low bioavailability. The baicalin is made of polyelectrolyte nanoparticles can improve the solubility of baicalin, accelerate the improvement of Baicalin in vitro release, in vivo absorption, increased bioavailability.First determine the polyelectrolyte nanoparticles dropping method for chondroitin sulfate solution is dripped into the chitosan solution. Then the average particle size, Zeta potential and encapsulation efficiency as index, the concentration of baicalin, chondroitin sulfate and the dosage of chitosan, chitosan concentration, chitosan solution pH, solution of chitosan in acetic acid content and speed and other factors of single factor test. To determine the initial proposal:baicalin concentration was less than2.5mg/mL; chitosan concentration was1.5～3mg/mL,0.2%acetic acid content; chondroitin sulfate and chitosan dosage ratio is less than7:10; chitosan solution pH is5.5; the speed700r/min. Determination of baicalin concentration, chondroitin sulfate and the dosage of chitosan, chitosan concentration, chitosan solution pH value is an important factor affecting the drug loaded polyelectrolyte nanoparticles according to the single factor test results.Then, in order to further optimize the preparation of drug loaded polyelectrolyte nanoparticles, with the average particle size, Zeta potential and the entrapment efficiency as the evaluation index, the effects of drug loaded polyelectrolyte nanoparticles3important factors (the concentration of baicalin concentration, chondroitin sulfate and the dosage of chitosan, chitosan solution) of central composite experimental design. Ultimately determine the optimal process is as follows:the concentration of baicalin solution is2.05mg/mL, the concentration of chitosan solution for2.01mg/mL and chondroitin sulfate and the dosage of chitosan is59.02%. Drug loaded polyelectrolyte nanoparticles prepared according to the optimal process, average grain diameter is168.22±2.08nm, Zeta potential was28.40±0.37mv, the entrapment efficiency was83.18 ±0.84%. At the end of the freeze drying process of drug loaded polyelectrolyte nanoparticles were optimized, determining the cryoprotectant mannitol and glucose were5%and2.5%.Simulating in vivo environment, studied different pH media download drug polyelectrolyte nanoparticles and drug release of baicalin by dialysis method. The experimental results show that:release model under different pH media are in accord with the Riger-Peppas equation. In pH4.0medium, release release of drug loaded polyelectrolyte nanoparticles was better than that of baicalin TC, the polyelectrolyte nanoparticles have to speed up the performance of drug release. The ionic strength in pH4.0phosphate buffer effects on the drug loaded polyelectrolyte nanoparticles, in vitro release results showed that, with increasing ionic strength of the release medium, the drug loaded polyelectrolyte nanoparticles release profiles.By gavage, respectively, the drug loaded polyelectrolyte nanoparticles lyophilized powder suspension (30mg/kg, baicalin/body weight of rats) and baicalin technical suspension (60mg/kg) in rats in vivo pharmacokinetics, determination results were processed by3p97software for the experiment, determined the optimal atrioventricular model the pharmacokinetic parameters were calculated. The experimental results show that:drug loaded polyelectrolyte nanoparticles and Baicalin in the distribution process. Rats were fitted to the two compartment model, two AUC respectively11.9741(μg/mL)*h and2.1925(μg/mL)*h, the dosage of different, AUC increased by10times, the polyelectrolyte nanoparticles can significantly improve the absorption of Baicalin, significantly improve the bioavailability of baicalin. Removal of drug loaded polyelectrolyte nanoparticles and baicalin TC rate CL (s) were2.50542mg/kg/h/(μg/mL) and27.3654mg/kg/h/(μg/mL), T1/2β were4.8597h and3.3071h, the drug loaded polyelectrolyte nanoparticles can prolong the baicalin in the body to eliminate, the release of drug.