Study On Sh-loaded Liposome/Thermosensitive Hydrogel Combination System For Intra-articular Administration

Sinomenine hydrochloride is the hydrochloride of sinomenine,an alkaloid monomer extractedfrom sinomenium acutum（Thunb.）Rehd et Wils, which is used to treat rheumatism, rheumatoid arthritis,anti-arrhythmia and other diseases in clinical for its definite therapeutic effect, however, sinomenine hasa short biological half-life, the commen form of the drug needs frequently administration, at the same time,it increases the release of histamine results in rash and other side effects. To overcome the shortcomings,Liposomes thermosensitive in situ gels of sinomenine for the treatment of RA by intra-articular injectionwas prepared in this article,hence improve the drug concentration in the target area, reduce its toxic sideeffects caused by systematic administration and prolong the action time.HPLC analysis method of sinomenine was set up for researching bulk drug pHysico-chemicalproperties and evaluating the quality of preparation in vitro. Method validation showed that the method isspecific, stable, and accurate.Investigated the solubility of sinomenine in water and different pH buffersaline as well as the apparent oil/water partition coefficient in the octanol-water system. The resultsshowed that the sinomenine has good solubility in water and has larger solubility in an alkalineenvironment.By single-factor test, evaluated the influence of prescription factors on the appearance andstability of sinomenine liposomes, and using central composite design to determine the optimalprescription with the encapsulation efficiency and drug loading as indicators. With injected soybeanlecithin and cholesterol as the membrane, using reverse pHase evaporation method combinated withammonium sulfate gradient method. The sinomenine liposomes were prepared by the optimal prescription, and its encapsulation efficiency was more than80%.The pHarmaceutical properties of prepared sinomenine liposomes were researched.Resultsshowed that the liposome were uniform spHerical, with an average diameter and zeta potential are86.64±28.84nm,-12.4±4.47mv, and the leakage rate of sinomenine liposomes stored at4℃is5.9%after7days. In vitro release results showed that the cumulative release is72.34%in the32h, and conformed toWeibull release model.With chitosan and glycerol as materials, using borax to adjust the pH, thermosensitive gels areprepared, and with the gelling temperature and time as indicators, applicating orthogonal design tooptimize its formulation and process, and pH of the final gel system is6.7, glycerol-chitosan ratio is2:10,the concentration of chitosan is20mg/ml. Prescription verification results: gelling temperature and timeare35℃and5min. On this basis, the freeze-dried powder of liposomes is further dispersed in the gel,whose gelling temperature turned into33℃, which can still be as optimal prescription. The releaseexperiment in vitro shows that sinomenine liposomes thermosensitive gel had an obvious advantagecompared with ordinary gels and liposomes in retarding the release of sinomenine hydrochloride.Sinomenine liposomes thermosensitive gels were placed in the refrigerator at4℃in order to investigateits sability, and the results showed that the stability of prepared gel is good in the investigated conditions.