目的 制备丹参酮II_A-丹酚酸B共载脂质体水凝胶(Lip-Gel@TSA/SAB),并进行离体皮肤渗透动力学研究。方法 采用薄膜分散-pH梯度法制备丹参酮II_A-丹酚酸B共载脂质体,再进一步负载于氧化透明质酸/琥珀酰壳聚糖,制得水凝胶Lip-Gel@TSA/SAB,进行扫描电子显微镜(SEM)表征;HE染色法研究Lip-Gel@TSA/SAB皮肤刺激性;动态透析法研究Lip-Gel@TSA/SAB的体外释药规律;改良Franz扩散池法研究Lip-Gel@TSA/SAB体外透皮渗透和真皮层滞留性能,计算并拟合药物释放模型。结果 脂质体在透射电子显微镜(TEM)下呈球状或类球状层状囊泡结构,平均粒径为(189.50±1.57)nm,粒度多分散系数(polydispersity index,PDI)为0.246±0.030,平均ζ电位为(−18.73±1.41)mV。Lip-Gel@TSA/SAB呈橘红色,质地均匀,内部为三维多孔网状结构。体外透皮试验表明,TSA-SAB Lips/Gel中TSA、SAB在48 h内单位面积累积透过量分别为(17.55±1.01)、(918.99±50.83)μg/cm²,真皮滞留量分别为(10.07±0.75)、(36.12±2.06)μg/cm²,符合Hixon-crowell方程和一级动力学模型。结论 Lip-Gel@TSA/SAB处方工艺合理,具有良好的透皮吸收性能和药物真皮滞留性能。

Objective To prepare tanshinone II_A-salvianolic acid B co-loaded liposomes hydrogel (Lip-Gel@TSA/SAB) and investigate permeation kinetics of skin in vitro. Methods Tanshinone II_A-salvianolic acid B co-loaded liposomes were prepared by thin film dispersion-pH gradient method, and then loaded on oxidized hyaluronic acid/N-succinyl chitosan hydrogel to obtain Lip-Gel@TSA/SAB. SEM was used to characterize Lip-Gel@TSA/SAB. HE staining was used to study the skin irritation of Lip-Gel@TSA/SAB. Dynamic dialysis was used to study the drug release of Lip-Gel@TSA/SAB in vitro. Modified Franz diffusion cell method was used to study the transdermal penetration and dermal retention of Lip-Gel@TSA/SAB in vitro, and the drug release model was calculated and fitted. Results Liposomes showed a spherical or sphere-like laminar vesicle structure under TEM with an average particle size of (189.50 ±1.57) nm, a PDI of 0.246 ±0.030, and an average ζ potential of (−18.73 ±1.41) mV. Lip-Gel@TSA/SAB was orange-red with homogeneous texture and a three-dimensional porous network structure inside. The transdermal test in vitro showed that the cumulative penetration amounts of TSA and SAB per unit area of TSA-SAB Lips/Gel within 48 h were (17.55 ±1.01) and (918.99 ±50.83) μg/cm², respectively, and the dermal retention of TSA was (10.07 ±0.75) μg/cm² while SAB was (36.12 ±2.06) μg/cm², which accorded with Hixon-crowell equation and first-order kinetic model. Conclusion Lip-Gel@TSA/SAB preparation process is reasonable, it has good transdermal absorption, drug dermal retention and high bioavailability.

R283.6

国家自然科学基金资助项目（82173982）；广东省自然科学基金资助项目（2022A1515011382）