A new vaginal delivery system of amphotericin B: a dispersion of cationic liposomes in a thermosensitive gel.
Amphotericin B (AmB) is used in the treatment of fungal infections; however, its clinical use is limited by its toxic side effects. In this study, AmB-loaded cationic liposome gels were formulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and cholesterol (CH) at a molar ratio of DOPE:DOTAP:CH = 4:5:1 in thermosensitive gel composed of poloxamer 407 (P407) and poloxamer 188 (P188). To enhance the solubility of AmB, 6 mol% of distearoyl phosphatidyl ethanolamine-polyethylene glycol was added prior to encapsulation of the drug into liposomes. Scanning electron microscopy was used to observe the AmB encapsulated cationic liposome gels. In vitro release, stability and cytotoxicity of AmB in cationic liposome gels were evaluated. The particle size and zeta potential of AmB-loaded liposomes were in the range of 400-500 nm and 40-60 mV, respectively. The thermosensitive gel at the ratio of P407:P188 = 15:15 (w/w) gelled at 37 degrees C, approximating body temperature. Encapsulation efficiency of AmB was approximately 50-60%, which was influenced by the ratio of AmB to lipid. Moreover, AmB-loaded cationic liposome gels were more stable and less toxic than free AmB. From these results, cationic liposome gel formulations may be useful for vaginal delivery of AmB.
Kang
June-Woo
JW
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Davaa
Enkhzaya
E
Kim
Ye-Tae
YT
Park
Jeong-Sook
JS
D000282:Administration, Intravaginal; D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002412:Cations; D002460:Cell Line; D002784:Cholesterol; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005782:Gels; D006801:Humans; D008055:Lipids; D008081:Liposomes / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D012995:Solubility
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002412:Cations; D005079:Excipients; D005229:Fatty Acids, Monounsaturated; D005782:Gels; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C068538:liposomal amphotericin B; D000666:Amphotericin B; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane