Preparation Of Albendazole Liposomes And Preliminary Studies Of Its Pharmacokinetics And Effect On Fasciola Hapatica In Goats

Albendazole(ABZ) was made into albendazole-poly-vinylpyrrolidone (PVP) coprecipitate, as a result its poorly water-soluble property was greatly improved. The X-ray diffraction spectra indicated that albendazole in the coprecipitate did not exhibit its crystalline property when the ratio was 1:5 (w/w) between ABZ and PVP. The orthogonal function spectrometric method was employed to measure the total amount of ABZ in liposomes suspension and ABZ encapsultec in liposomes, without any nonspecific interference possibly caused by lipid. The detecting wave length was range from 277 to 307 nm with interval of 6nm.This assay was simple, practicable and reproducible. The recovery rate was up to 98.8 ±0.5% (n=10). The ABZ encapsulated into liposomes and the free were separated with sephadex gel filtration.The separating conditions were: sephadex G-100, 0.8 ×33cm column, 0.5 ml loading volume and elution with dis-vtilled water. By using L9 (3~4) orthogonal design and taking encapsulation efficiency as optimization factor, we have selected the best prescription and technique for preparing liposomes with freeze-thawing (FT) and freeze-drying (FD) method. The optimal conditions of prescription were as followed: The ratio between drug and lipid was 1:48(w/w) and between cholesterol and lecithin was1 i6(mol/mol). Outer aqueous medium was distilled water* Under these conditions the encapsulation efficioncy of ABZ liposomes prepared by FT or FD method was 59 ?O + 0,665&*or 62.0 +0,65$ respectively. The stability of liposomes prepared by FT and FD methods were measured on the basis of ABZ leakage from liposomes. It was found that FD-prepared liposomes were more stable than FT-prepared liposomes. We have also observed the lipo-some structure under electron microscope. The results showed that most' of vesicles were multilamellar with size range from 1 to 6 A3 and vesicles of 1-2/1 were more than 50 percent. The influences of 00 of radiation and boiled sterilization on liposomes have been investigated. The radiation at a dose of 1X10 rad was found to be less influenced than boiled sterilisation on liposomes*The concentration of ABZ and its two major metabolites, sulfoxide (SX) and sulfone (SO), were measured in plasma orally given ABZ at a dose of 10 mg/kg or intraperitoneally given ABZ liposomes suspension at a dose of 5 mg/kg by means of reverse high-performance liquid chromatography. ABZ was not detectable in plasma at any time in moat of goats whether the drstg was given orally or intraperitoneally. SX and SO in plasma were detectable but the individual differecnce was 9ignifi?-cant. After oral or intraperitoneal administration, the major parameters were: SXs AUC 19.4 + 10.7 or 3*3 ? 2.3/ug/ml?h;ti/2ke 7.7 ? 2.2 or 3.0 + 1.6 hi Cmax 1.129 + 0.732 or 0.624 i 0<535/ug/ml;Tmax 13.6 ± 2.2 or 3 h;Tcp 28-32 or 6-16 h,'SO? AUC 21.6 ? 20.8 or 6.19 + 3?1.6yug/ml.h;ti/ke 11.8 ? 4.1 or 10*2+ 3?3 h;Cmax 1.053 ± 0.946 or 0.505 + 0.295>ug/ml;Tmax 22.4 ? 2.2 or 4.4 It 3*2 h;Tcp 32-40 or 12-20 h? The resultsshowed there was great difference between two dosage forms.Forty goats with natural Fasciola hepatica infection were randomly allotted to 4 groups of 10 goats each? group 1, no treatment (controls)$ group 2, ABZ suspension given orally at 10 mg/kg? group 3, ABZ lipaoraes suspensipn given intraperitoneally at 3 mg/kgj group 4, ABZ liposomes suspension given intraperitoneally at 5 mg/kg. Eggs per gram faeces (EPG) were counted before treatment and four weeks after treatment. Eggs reduction rate(ERR)was determinated by following formula sBPG before treatment-BPG affter treatmentEPG before treatmentERR of group 2,3,4 were 71.8, 98.1, 99*5%, respectively The results showed that both ABZ oral suspension and ABZ liposomes suspension were active against Fasciola hepatica* By comparing with ABZ suspension ABZ lipo-aomes had many advantages such as higher efficacy, lower doae, more precise dosage and easier administration.