Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis.
To develop more effective treatment for vaginal candidasis, clotrimazole (CT) was formulated in mucoadhesive thermosensitive gels (MTG). Several MTG formulations composed of poloxamers (P) 407, 188, and polycarbophil (PC) were prepared. P188 and PC increased the mucoadhesiveness but reduced the syringebility of liquid forms of the gels. Based on the balance between the mucoadhesiveness and syringebility, MTG composed of P407/P188/PC (15/15/0.2 or 15/20/0.2) were further studied. Of the two MTG, the formulation with 15% of P188 gelled at higher temperature and revealed lower elastic modulus. In vitro, sustained release of CT from MTG was observed. In vivo antifungal activity of CT, tested against Candida albicans vaginitis in female rats, was significantly prolonged after vaginal delivery using MTG. At 10 days post-dose, the c.f.u. of C. albicans was more than 10(4)-fold decreased in MTG-treated groups. Moreover, the vaginal delivery of CT in MTG enhanced the viability of epithelial cells without affecting the morphology of vaginal mucosa. These results indicate that CT-containing vaginal MTG might be further developed for safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.
Chang
Jung Yun
JY
National Research Laboratory for Drug and Gene Delivery, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
Oh
Yu-Kyoung
YK
Kong
Hak Soo
HS
Kim
Eun Jung
EJ
Jang
Dong Deuk
DD
Nam
Ki Taek
KT
Kim
Chong-Kook
CK
D000269:Adhesives / Q000737:chemistry*; D000282:Administration, Intravaginal; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003022:Clotrimazole / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005782:Gels; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D013696:Temperature; D013997:Time Factors; D014621:Vagina / Q000473:pathology; D014627:Vaginitis / Q000188:drug therapy* / Q000382:microbiology
D000269:Adhesives; D000935:Antifungal Agents; D005782:Gels; D003022:Clotrimazole