Preparation And Targeting Release Behavior Of Drug Loaded Carbohydrate Polymer Nanoparticles

In recent years, oral colon targeting drug delivery system(OCDDS) has attracted many attentions due to its advantages, such as higher availability and reduced side effects. Among all published OCDDS, systems based on natural polymers got much more attentions.In this study, two typical natural polymers, namely konjac glucomannan and sodium alginate, which can be hydrolyzed by colonic enzyme, were chosen as raw materials. Electrospray which has been reported to produce polymer particles with controllable and monodisperse in size was modified to synthesize OCDDS. Then the feasibility for preparation of OCDDS in nano-size with the two polymers as raw materials and diclofenac sodium as model drug through a modified electrospray setup was investigated. The parameters and production process for preparation of OCDDS in nano-size were optimized and studied in detail, and the relationship between release profiles of model drug from OCDDS with particle size as well as cross-linking process was discussed. The main results are as follows:(1) Diclofenac sodium-loaded Konjac glucomannan/Alginate(KGM/SA) nanoparticles were successfully prepared with the modified electrospray setup when the mixture of ethanol and water was applied as the solvent of the two polymers.(2) Both the electrospray parameters and solvent composition have significantly effect on the particle size. The optimized conditions were: voltage of 14.8kV, working distance 1.5cm and the flow rate 0.4mL/h; the ratio of Konjac glucomannan to Sodium alginate 0.075:0.075w/v%, the ratio of model drug to carrier polymers 1:2w/w%, the concentration of ethanol 27.5 v/v%, the solvent evaporation temperature 47?, and evaporation height 20 cm, respectively. Under those conditions, the spherical nanoparticles(249.3±44.6nm) with relatively narrow size distribution were successfully produced. The entrapment efficiency(EE) and loading capacity(LC) of OCDDS were up to 93.72±2.65% and 31.24±0.89%, respectively.(3) In vitro drug release study indicated that:(1)the system has achieved the purpose of colon targeting and sustained release of drug, which could effectively reduce the irritation and improve the bioavailability of drugs which exhibited the typical characteristics of OCDDS.(2) Particle size influenced the drug release properties effectively, and the mechanism of drug release would not be varied by the particle size although the release rate of nanoparticles was much faster than that of microparticles. So it is not necessary to tune chemical property and the composition of OCDDS to tailor release rate, we may only control particle size to meet tailored release profile for a variety of applications in medical fields.(4) The characteristics of colon targeting and sustained release of KGM/SA particles will not be changed although the drug release pattern can be adjusted and controlled easily with the type of cross-linking agent, which implied that it is possible to develop a series of OCDDS with KGM/SA also.