title: Enhanced anti-tumor activity and alleviated hepatotoxicity of clotrimazole-loaded suppository using poloxamer-propylene glycol gel.
abstract: To develop a novel clotrimazole-loaded poloxamer-based suppository with enhanced anti-tumor activity and alleviated hepatotoxicity, the melting point of various formulations composed of P 188 and propylene glycol were investigated. The dissolution and anti-tumor activity of clotrimazole delivered by the poloxamer-based suppository was performed. Furthermore, the hepatotoxicity of clotrimazole was carried out after its rectal administration compared to oral administration in mice. The poloxamer mixtures composed of P 188 and propylene glycol were homogeneous phases. P 188 greatly affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 188/propylene glycol (70%/30%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. The ratio of P 188/propylene glycol greatly affected the dissolution rates of clotrimazole from poloxamer-based suppository. Dissolution mechanism analysis showed the dissolution rate of clotrimazole from poloxamer-based suppositories was independent of the time. The clotrimazole-loaded suppository with P 188 and propylene glycol could not irritate or damage the rectal tissues of rats and gave the improved anti-tumor activity in a dose-dependent manner at mouse. Furthermore, its rectal administration decreased the hepatotoxicity compared to oral administration. Thus, the poloxamer-based solid suppository system with clotrimazole/P 188/propylene glycol was an effective rectal dosage form for the treatment of tumors with alleviated adverse effects.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jing Ji
authors.initials: JJ
authors.lastname: Xuan
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Paek
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Woo
authors.forename: Mann Hyung
authors.initials: MH
authors.lastname: Lee
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003022:Clotrimazole / Q000008:administration & dosage* / Q000633:toxicity; D005782:Gels; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020442:Poloxamer / Q000008:administration & dosage; D019946:Propylene Glycol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013488:Suppositories
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D013488:Suppositories; D020442:Poloxamer; D019946:Propylene Glycol; D003022:Clotrimazole