Preparation, in Vitro and in Vivo Evaluation of Liposomal/Niosomal Gel Delivery Systems for Clotrimazole

Abstract

Clotrimazole, which is an imidazole derivative antifungal agent, was widely used for the treatment of mycotic infections of the genitourinary tract. To develop alternative formulation for the vaginal administration of clotrimazole to provide sustained and controlled release of appropriate drug for local vaginal therapy, liposomes/niosomes were evaluated as delivery vehicles. To optimize the preparation of liposomes/niosomes with regard to size and entrapment efficiency, multilamellar liposomes/niosomes containing drug were prepared by lipid hydration method. The prepared liposomes/niosomes were incorporated into 2% carbopol gel, and the systems were evaluated for drug stability in phosphate-buffered saline (pH 7.4) and simulated vaginal fluid at 37 +/- 1 degrees C. Further, the vesicle gel system was evaluated by antifungal activity and tolerability on tissue level in rat.

Development of Naftifine Hydrochloride Alcohol-Free Niosome Gel

“…Secondly, niosomes may help localize the drug at the site of infection, in the vicinity of the infective fungus leading to increased efficacy. This is because the entrapment of a drug in vesicles improves solubility and helps in the localized delivery and deposition at the site of action (Ning, Guo, Pan, Chen, & Gu, 2005).…”

Treatment of cutaneous candidiasis through fluconazole encapsulated cubosomes

“…In addition to Fnz, itraconazole and ketoconazole have been proven to be active against Candida species [4]. Ketoconazole and clotrimazole (as liposomal/niosomal proliposomes) have been reported to be significantly therapeutically effective when given in solutions [21,22,24].…”

New strategies for local treatment of vaginal infections

“…Limited stability in aqueous formulations represents one of their major drawbacks [154]. Concerning the treatment of vaginal infections, several works have been done studying liposomes for the formulation of antifungals [154,[172][173][174] and antibacterials [172,175] …”

“…Liposomal based bioadhesive and thermogelling systems have been further studied in vitro as final dosage forms for some of these liposomes. For instance, research groups working independently showed that the inclusion of different drug-loaded liposomes (based on egg phospholipids), in a Carbopol® 974P bioadhesive gel improved liposome stability in a media simulating the vaginal environment (37ºC; simulated vaginal fluid with pH 4.2) while delaying the release of clotrimazole[174,176] and metronidazole[176]. Ning et al further tested multilamellar vesicles, both liposomes and niosomes (which are vesicles similar to liposomes and prepared with non-ionic surfactants, in this case Span®40) in an oophorectomized female rat Candida infection model[174].…”

“…For instance, research groups working independently showed that the inclusion of different drug-loaded liposomes (based on egg phospholipids), in a Carbopol® 974P bioadhesive gel improved liposome stability in a media simulating the vaginal environment (37ºC; simulated vaginal fluid with pH 4.2) while delaying the release of clotrimazole[174,176] and metronidazole[176]. Ning et al further tested multilamellar vesicles, both liposomes and niosomes (which are vesicles similar to liposomes and prepared with non-ionic surfactants, in this case Span®40) in an oophorectomized female rat Candida infection model[174]. The liposome/niosome gel formulations showed prolonged and enhanced antifungal activity when compared with a commercial ointment and with a gel with plain drug, after a 7 day treatment (dose 25mg/kg), with no histopathological deleterious changes in vaginal tissues found (24h post dose).A Carbopol® gel was also used by Karimunnisa and Atmaran to achieve sustained release of ciclopiroxolamine.…”