Liposomes as an ocular delivery system for fluconazole: in-vivo study

The purpose of this study was to formulate topically effective controlled release ophthalmic fluconazole liposomal formulations using the reverse-phase evaporation technique. Soya bean phosphatidylcholine [PC] and cholesterol [Ch] in specific weight ratios were used. Selected formulations were tested for their in-vivo ocular antifungal effect. These included the neutral, the positively [using stearyl amine] and the negatively [using dicetyl phosphate] charged liposomes. A reproducible model of Candida keratitis in rabbits was performed and the effects of the prepared liposomes were better than a solution of fluconazole. The order of fluconazole liposomal formulations according to the time to achieve complete healing is arranged in a descending order: negatively charged liposomes > positively charged liposomes > neutral liposomes [7:4] > neutral liposomes [5:5] > fluconazole solution. The frequency of instillation was decreased; also, the time of ulcer healing was decreased. It was concluded that the use of liposomes as a drug delivery system could contribute to the enhancement of the effect of fluconazole in the eye

Liposomes as an ocular delivery system of fluconazole: in-vitro studies

The purpose of this study was to formulate topically effective controlled release ophthalmic fluconazole liposomal formulations. Reverse-phase evaporation technique was used for the preparation of fluconazole liposomes consisting of phosphatidylcholine [PC] from soyabean and cholesterol [Ch] in weight ratios of [9:1], [7:2], [7:3], [7:4], [6:4], [7:6] and [5:5] with or without stearylamine [SA] or dicetyl phosphate [DP] as positive and negative charge inducers, respectively. The prepared liposomes were evaluated for their in-vitro release. The release mechanism was found to follow Higuchi and first order kinetics. Increasing cholesterol weight ratio in the prepared liposomal formulations progressively decreased the release of fluconazole from the vesicles. The positively charged liposomes showed slower rate of drug release compared to neutral ones. Negatively charged liposomes showed slight increase in the release rate and extent of fluconazole from the liposomal formulations 5:5:0.25 and 5:5:0.5; in comparison with neutral ones. Further increase in the amount of dicetyl phosphate 5:5:1 resulted in a significant decrease in the release rate. Four fluconazole liposome eye drops were prepared. Physical stability study including, visual appearance, particle size and amount of drug leakage from liposome eye drops were studied. Approximately 82.82%, 76.55%, and 70.90% of fluconazole was retained in negative, positive and neutral liposomal ocular formulations up to a period of 24 weeks at 5°C