Thermosensitive mucoadhesive gel formulation loaded with 5-Fu: cyclodextrin complex for HPV-induced cervical cancer

• Published in: Journal of Inclusion Phenomena and Macrocyclic Chemistry 2007-04, Vol.57 (1-4), p.363-370
• Main Authors: Bilensoy, Erem, Çırpanlı, Yasemin, Şen, Murat, Doğan, A. Lale, Çalış, Sema
• Format: Article
• Language: English
• Subjects: Human papillomavirus
• ISSN: 0923-0750; 1573-1111
• DOI: 10.1007/s10847-006-9259-y

Human Papilloma Virus (HPV) infections are the major cause of cervical cancers. To achieve a better therapeutic efficacy and patient compliance in the treatment for HPV-induced cervical cancers, anticancer agent 5-fluorouracil has been formulated in a vaginal gel using the thermosensitive polymer Pluronic super( registered ) F127 together with alternative mucoadhesive polymers e.g., hyaluronic acid, Carbopol 934 and hydroxypropylmethylcellulose. To increase its aqueous solubility and to achieve the complete release of 5-FU from the gel, the drug was incorporated as its inclusion complex with 1:1 molar ratio with either beta -cyclodextrin or hydroxypropyl- beta -cyclodextrin. Following the characterization of drug:CD complexes, thermosensitive gel formulations containing different mucoadhesive polymers and the drug in free or complexed form were characterized in vitro by determining the gelation temperature and the rheological behavior of different formulations along with the in vitro release profiles of these formulations in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin accelerated the release of 5-FU with the exception of formulation containing Carbopol 934 as mucoadhesive polymer. As far as rheological properties are concerned, favorable thermosensitive in situ gelling properties were obtained with formulations containing HPMC as mucoadhesive polymer. Complete release of 5-FU from gels were obtained with both complexes of beta -CD and HP- beta -CD and cytotoxicity studies against HeLa human cervical carcinoma cells demonstrated that 1% 5-FU:CD complexes were equally effective as 1% free 5-FU indicating better therapeutic efficacy with lower dose.