Study On Cucurbitacin B-PLGA Prolonged Action Microspheres

As a new kind of sustained-release drug delivery system, microspheres have been widely investigated. It exerts sustained-release effects through the specific skeleton material-PLGA, which could biodegrade into harmless water and CO2. It has been approved by FDA, using as an adjuvant. Therefore Cucurbitacin B for treating chronic hepatitis can be prepared into prolonged action and slow-release injectable microspheres, which can reduce drug toxicity, and adverse reaction of gastrointestinal, raise bioavailability and prolong drug performing time.In this paper, Cucurbitacin B was chosen as a lipophilic model drug and D,L-lactide/glycolide copolymer (PLGA) was used as a carrier to prepare biodegradable and biocompatible microspheres (MS) with modified emulsification-solvent evaporation method. Single factor investigation was used to screen the factors and levels influencing microspheres preparation.Central composite design-response surface methodology is applied to optimize the formulation. The optimal conditions are proved to be 1.4% PVA and drug to polymer ratio 6.65%. The microspheres are spherical and have a smooth surface. Mean diameter and encapsulation efficiency are 56.18μm and 80%, respectively.In vitro modified direct drug-release method was operated in in vitro release test. HPLC method for determination of cucurbitacin B content in medium was established. The cumulative release is about 76%. At the same time an accelerated release method was developed. Moreover accelerated release rate correlates well with long release rate. And this demonstrates that short accelerated release rate could predict long release rate in vitro.The in vivo process of Curcubicatin B was accessed with mouse model. Determinating methods for cucurbitacin B content in plasma and muscles were established. The results show that the T1/2 is 1.737h and AUC(0-∞) is 1.963 mg/L×h. While the pharmacokineitics of Curcubicatin B-PLGA microsphere after s.c. indicates that the T1/2 is prolonged to 159.582 h, Cmax is 619.96 ng/mL, AUC(0-∞) is 124.201mg/L×h, respectively. The drug is sustained released from microspheres in 33 d, and the drug concentration curve of plasma in mouse presentes triphase of burst release, plateau phase and storms release phenomenon.In the studies of in vivo-in vitro correlation, in vivo release rate was calculated by measuring the amount of drug remaining in microspheres excised from the injection site. The results show that a good correlation is obtained between in vivo release percent and in vitro release percent.In the biocompatibility study of MS, the Curcubicatin B-PLGA microsphere was evaluated with pathological examination of mice skin after treatment. The results show that Curcubicatin B-PLGA microspheres treatment induces slight inflammation response in mouse skin, but no sign of infiltration liquid accumulation is found. There are not obvious angiogenesis and fiber hyperplasia. So it is clear that Curcubicatin B-PLGA microsphere possesses a good biological compatibility.