Donalisio Manuela, Leone Federica, Civra Andrea, Spagnolo Rita, Ozer Ozgen, Lembo David, Cavalli Roberta
Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole 10, Orbassano, 10043 Turin, Italy.
Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, Italy.
Pharmaceutics. 2018 Apr 10;10(2):46. doi: 10.3390/pharmaceutics10020046.
Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin. Biological studies were performed on the Vero cell line infected by HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a spherical shape, a size of about 200 nm, and a negative zeta potential of about 40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release demonstrated that the percentage of acyclovir delivered from the nanospheres was approximately 30% after six hours. The in vitro skin permeation studies confirmed an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a higher antiviral activity than that of free acyclovir against both the HSV-1 and the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning microscopy confirmed that the NS are taken up by the cells.
阿昔洛韦不是被动渗透的理想候选药物，因为其极性和溶解度限制了其进入角质层的分配。这项工作旨在开发一种用于阿昔洛韦递送的新型局部制剂。通过改进的纳米乳液模板法制备了新型壳聚糖纳米球（NS）。通过动态光散射（DLS）、透射电子显微镜（TEM）和体外释放研究对壳聚糖NS进行了表征。使用Franz扩散池并配备猪皮进行体外皮肤渗透实验。对感染单纯疱疹病毒1型（HSV-1）和单纯疱疹病毒2型（HSV-2）毒株的非洲绿猴肾细胞系（Vero细胞系）进行了生物学研究。负载阿昔洛韦的壳聚糖NS呈球形，大小约为200nm，zeta电位约为-40.0mV。药物的负载量约为8.5%。体外释放表明，六小时后从纳米球中释放的阿昔洛韦百分比约为30%。体外皮肤渗透研究证实渗透的阿昔洛韦量有所增加。阿昔洛韦-NS复合物对HSV-1和HSV-2毒株均显示出比游离阿昔洛韦更高的抗病毒活性。负载阿昔洛韦的NS没有显示出抗增殖活性，也未检测到NS诱导的细胞毒性迹象。共聚焦激光扫描显微镜证实细胞摄取了NS。
