Studies On Acyclovir Liposomal Eye Drops

The main drawback of traditional eye drops is their poor bioavailability. After administration, they are diminished by tear fluid quickly. Compared with them , liposomal eye drops can prolong the residence time in precorneal and build the ability to penetrate into aqueous humor therefore promote the bioavailbility .Using acyclovir as model drug,liposomal eye drops were designed and a series of relative researches were carried out.A method was developed to determine the encapsulation efficiency of ACV-containing liposome preparations by chloroform extration-UV spectrophotometry and protamine precipitation-UV spectrophotometry. The method was simple and accurate and easy to operate.The Reverse-Phase evaporation (REV) method was employed for the manufacture of acyclovir liposomes from natural soyabean lethicin. The Encapsulation Efficiency (EN) of acydovir-containing liposome (ACVL) was determined and some factors which may affect the EN such as thedrug-lipid ratio, ionic strength were investgated.In order to ensure excellent stability and to obtain higher encapsulation efficiency, a uniform design was carried out and obtained the optimum component of liposome and the average encapsulation efficiency was above 62%. In accelerated tests, it was found that the liposome suspension was stable at low temperature in oxygen-free atmosphere and protected from light.The physicochemical properties of liposomes were studied. Themorphological characteristic of liposome samples was revealed under transmission electron microscope. The surface electric potential , pH, and the surface tension of acyclovir liposomes is -78.87 mV,7.36, 57.58+10-3N/m respectively. The rheological curve proved that ACVL was non-Newtonian fluid and its viscosity was decreased by high temperature.The clearance of eyedrop was found to exhibit a biphasic pattern by y-scintigraphic technique. At the end of 7 min only less than 20% of the applied solution was in contact with the corneal surface. For positive and negative liposomes,the residence time of radioactive marker was significantly prolonged and the retentive effect was superior to blank solution.The elimination half-life time of positive, negative and PBS was 51.52min, 14.75min and 4.18min respectively.The toxicity of ACV liposome preparation was investigated by using index of eye irritation experiments .The conclusion was that the liposome preparation had no irritation.The effects of ACV -containing liposome preparation on herpes simplex keratitis in conscious rabbits indicated that the liposome preparation markedly increased the index of treatment and was more effective than current acyclovir eye drops. Compared with the other two groups, there was statistical significance among them. Virus was isolated and TCID50 (tissue culture infective dose) was calculated. The results showed the same conclusion as clinical observance.