Fluconazole-loaded liposomes for ocular delivery: characterization and antifungal activity

Fluconazole loaded liposomes were prepared using reverse phase evaporation technique for ocular delivery of the drug. Characterization of fluconazole liposomes including; particle size and physical morphology were studied. The effects of different variables [cholesterol weight ratio and charge type] on the loading efficiency of liposomes as well as particle size were determined. Inclusion of cholesterol in liposomal formulations improved the encapsulation of fluconazole into liposomes at certain Phosphatidylcholine: Cholesterol [PC: Ch] weight ratios further increase in cholesterol content resulted in a decrease in the encapsulation percent of the drug. A significant increase in the encapsulation at ratio 7:3 was noticed. At ratio 7:6, the encapsulation significantly decreased. Incorporation of stearylamine [SA] into liposomes decreased the loading efficiency of fluconazole at ratio [PC: Ch: SA] 5: 5: 0.25 followed by insignificant increase in the entrapment of the drug into liposomes at ratio 5: 5: 0.5. On the other hand, addition of dicetyl phosphate [DP] into liposomes resulted in a significant increase in fluconazole encapsulation into liposomes at all tested [PC: Ch: DP] ratios. The loading efficiency of the neutral liposomes was found to be in between those of positively and negatively charged liposomes. The particle size studies showed that, increasing cholesterol amount, led to an increase in the particle size. While increasing stearylamine and dicetyl phosphate led to decrease in the particle size of liposomes. An in-vitro study was done to know the effect of fluconazole loaded liposomes on different fungi isolated from eye

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

Effect of cardiopulmonary bypass on the pharmacokinetics of intravenous paracetamol [Propacetmol hydrochloride]

Recently, intravenous paracetamol [propacetamol] is commonly in use as analgesic and antipyretic after surgery. To our knowledge, the pharmacokinetic of intravenous paracetamol in patients undergoing cardiac surgery with cardiopulmonary bypass were not previously described. This study was designed to investigate the effect of cardiopulmonary bypass on the pharmacokinetics of single intravenous dose of paracetamol in adult patients undergoing coronary artery bypass surgery with hypothermic cardiopulmonary bypass. Nine patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass using mild hypothermia 30°C were selected. Intravenous paracetamol [2g single dose of Propacetamol hydrochloride [Pro-Daflgan UPSA, Fr]] was infused over 10 min and arterial samples were taken starting from 20 min after infusion and afterwards over 8 hours from infusion. Plasma paracetamol concentrations were measured by high-pressure liquid chromatography. The pharmacokinetics of paracetamol was calculated assuming a linear one compartment model with instantaneous input and first order output. The pharmacokinetic data were reported as mean [SD]. ANOVA was used to compare between the pharmacokinetic parameters before and after CPB. C[max] 10.19 [0.9545] mg.litre[-1] appeared 20 min after the end of infusion [experimentally]. Mean clearance [CL] was significantly reduced by about 40% in post CPB [prebypass 0.589 [0.1069] L.h[-1].kg[-1] vs. 0.357 [0.0394] L.h[-1].kg[-1] after CPB, P < 0.05]. The elimination rate constant [Ke] was significantly reduced by about 43% after CPB compared to pre-bypass values. However, the elimination half-life [t[1/2]] was significantly increased from 1.380 h before bypass to 2.431h in post bypass period. It appears from this study that hypotuermic cardiopulmonary bypass can affect the kinetic profile of IV paracetamol in patients undergoing coronary artery bypass graft surgery, and these changes should be considered while using this drug in such situations