DOUBLE LIPOSOMES MEDIATED DUAL THERAPY OF AIDS RELATED OPPORTUNISTIC FUNGAL INFECTIONS AND AIDSAbstract
To deliver zidovudine (AZT) to asialoglycoprotein receptors, drug-containing galactosylated liposomes were prepared. Simultaneously, miconazole nitrate (MCZ) was entrapped in the outer liposomal bilayer of double liposomes for the treatment of opportunistic fungal infections. Galactosylated liposomes were entrapped in double liposomes. The galactose binding Ricinus communis lectin was used for the determination of in vitro ligand binding capacity. Percent cumulative drug release from double liposomes with inner uncoated liposomes (DLMA) and inner galactosylated liposomes (Gal-DLMA) were compared. Cellular drug uptake studies were performed. In vivo antifungal activity, plasma distribution and hepatic localization study were performed in albino rats. Percent cumulative drug release of AZT from inner liposomes was significantly higher with DLMA as compared to Gal-DLMA. MCZ uptake was 4.7 times greater after encapsulation in liposomes irrespective of inner liposome coating and maximum AZT uptake (7.9 fold enhancement) was observed from double bilayer galactosylated liposomes as compared to free drug. MCZ encapsulated in double liposomes was able to reduce CFU (colony forming units) values to a significant extent in various tissues. Gal-DLMA remains in the body for longer period of time. In case of Gal-DLMA administration significant amount of AZT was recovered from parenchymal cells of liver as compared to non-parenchymal cells. Galactosylated lipid substances allowed liver specific uptake of AZT at enhanced parenchymal: non-parenchymal selectivity ratios and at the same time could deliver MCZ for treatment of fungal infections. Galactosylated liposomes further entrapped in liposomes hold much promise in dual drug delivery.
Babu Ram Garg*, Arun Kumar, Minakshi Garg, Jayamanti Pandit and Narendra K. Jain
Principal, Himachal Institute of Pharmacy, Poanta Sahib, Distt. Sirmour (H. P.), India
18 October, 2010
21 November, 2011
14 January, 2011
01 March, 2011