紫杉醇壳聚糖自组装纳米胶束冻干粉针的制备及理化性质研究

 目的紫杉醇壳聚糖自组装纳米胶束冻干粉针的制备及理化性质评价。方法以载药量、包封率和粒径为指标考察直接溶解法、乳化溶剂挥发法、透析法等载药工艺,筛选冻干保护剂及用量,测定其粒径、ξ电位、pH值、渗透压,并评价其稀释稳定性,以透射电镜(TEM)观察其形态,DSC和WAXD对其进行理化性质表征。结果最佳载药工艺为透析法,最佳冻干保护剂为15g·L^-1甘露醇,紫杉醇壳聚糖载药纳米胶束(PTX-OCC)载药量和包封率分别高达34.4%和89.3%;载药后,纳米胶束粒径由165.6nm增长到176.4nm,ξ电位则由-30.2mV增至-50.9mV;PTX-OCC溶液稀释至0.8g·L^-1,放置于25℃稳定长达9d;TEM照片显示,OCC及PTX-OCC皆为规则球状结构,粒径分布均匀;OCC及PTX-OCC pH值、渗透压皆符合静脉注射要求;DSC,WAXD实验结果表明,药物以无定型或固态溶液的形式存在于胶束骨架中。结论N-辛基-O,N-羧甲基壳聚糖(OCC)纳米胶束对紫杉醇具有优越的载药性能,为潜在的优良的可静脉注射的难溶性药物增溶载体。

Preparation of Paclitaxel-loaded Chitosan Self-assembled Nanomicelles Freeze-dried Powder for Injection and Its Physicochemical Characterization

OBJECTIVE To prepare and characterize paclitaxel loaded N-octyl-O,N-carboxymethyl chitosan self-assembled nanomicelles (PTX-OCC). METHODS Several drug-loading methods including direct dissolution method,oil/water emulsion and dialysis method were evaluated using drug loading content,drug encapsulation efficiency and size as indexes. PTX-OCC was characterized by dynamic light scattering,Zeta potential,pH,osmotic pressure and transmission electron microscopy (TEM). The physical properties were further analyzed by wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC). RESULTS Dialysis was optimized as the best method to encapsulate PTX into the self-assembled nanomicelles, and mannitol (1.5%,w/v) was selected as the lyophilized protectant to prepare the lyophilized PTX-OCC. PTX loading amount in the OCC micelles was 34.4% with 89.3% encapsulation efficiency. The size of OCC was 165.6 nm with Zeta potential -30.2 mV. When PTX was loaded into OCC,the size of PTX-OCC was increased to 176.4 nm with Zeta potential -50.9 mV. PTX-OCC micellar systemshowed good dilution stability for 9 d at 25 ℃. The pH and osmotic pressure of PTX-OCC were both qualified as iv administration preparation. TEM images of OCC and PTX-OCC showed a spherical shape. DSC and WAXD of PTX-OCC indicated that paclitaxel was transferred from the crystalline state to amorphous state after loading. CONCLUSION The present OCC micelles could be potentially useful as a novel delivery system for anticancer drug paclitaxel.