Chutoprapat Romchat, Chan Lai W, Heng Paul W S
GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, Singapore.
J Pharm Pharmacol. 2014 Jul;66(7):943-53. doi: 10.1111/jphp.12222. Epub 2014 Feb 18.
To investigate the influence of the hydrophilic polymer, polyvinylpyrrolidone (PVP) on the ex-vivo permeability of the poorly water-soluble photosensitizer, chlorin e6 (Ce6) using the chick chorioallantoic membrane (CAM) model.
The CAM was removed from the fertilized chicken egg at embryo age of 15 days. The permeation profiles of Ce6 and PVP complexes (Ce6-PVP) at 1:0, 1:1, 1:10, 1:50 and 1:100 w/w in different pH conditions were first studied using the CAM model with Franz diffusion cell over 8 h. The solution viscosity of the formulations and apparent solubility of Ce6 were also investigated.
The permeability of Ce6 was found to be directly proportional to the amount of PVP used and the apparent solubility of Ce6. Permeability was only marginally affected by the solution viscosity of the formulations. The permeability of Ce6 was lowered in the acidic pH. Ce6-PVP at 1:100 w/w gave the highest percentage release of Ce6 across the CAM, with 23% at pH 3 and 55% at pH 7.4, after 8 h, respectively.
The present work suggests that PVP had served as penetration enhancer for the poorly water-soluble Ce6 and the CAM can serve as a useful biological membrane model for preclinical permeability study of biological and pharmaceutical substances. The Ce6-PVP formulation at 1:100 w/w can be applied for the further clinical investigation.
利用鸡胚绒毛尿囊膜（CAM）模型，研究亲水性聚合物聚乙烯吡咯烷酮（PVP）对水溶性差的光敏剂二氢卟吩e6（Ce6）体外渗透性的影响。
在胚胎发育15天时，从受精鸡蛋中取出CAM。首先使用Franz扩散池的CAM模型，在不同pH条件下，研究1:0、1:1、1:10、1:50和1:100 w/w的Ce6与PVP复合物（Ce6-PVP）在8小时内的渗透情况。还研究了制剂的溶液粘度和Ce6的表观溶解度。
发现Ce6的渗透率与所用PVP的量和Ce6的表观溶解度成正比。渗透率仅受制剂溶液粘度的轻微影响。在酸性pH条件下，Ce6的渗透率降低。1:100 w/w的Ce6-PVP在CAM上的Ce6释放百分比最高，8小时后，在pH 3时为23%，在pH 7.4时为55%。
目前的研究表明，PVP可作为水溶性差的Ce6的渗透促进剂，CAM可作为生物和药物物质临床前渗透性研究的有用生物膜模型。1:100 w/w的Ce6-PVP制剂可用于进一步的临床研究。
