Marjan Daeihamed1, Azadeh Haeri1, Seyed Nasser Ostad2, Masoud Faghih Akhlaghi3, Simin Dadashzadeh1,4. 1. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Toxicology & Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Medicinal Chemistry, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran. 4. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
AIM: In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated. MATERIALS & METHODS: Different doxorubicin-loaded liposomes were prepared, characterized and orally administered to 18 groups of rats. Plasma concentrations of doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and transport of optimum liposomes were investigated. RESULTS: After studying different factors, a fourfold increase in oral bioavailability was achieved with the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug ratio = 10). The extent of drug's first-pass metabolism as well as endocytosis of nanoparticles were markedly affected by liposomal formulation. CONCLUSION: Oral absorption is highly dependent on liposomal properties, and optimum formulations are effective for low-permeability drugs.
AIM: In this study, the effects of liposome characteristics on oral absorption of doxorubicin, as a hydrophilic low-permeability drug, were investigated. MATERIALS & METHODS: Different doxorubicin-loaded liposomes were prepared, characterized and orally administered to 18 groups of rats. Plasma concentrations of doxorubicin and its aglycone metabolite were measured, and Caco-2 uptake and transport of optimum liposomes were investigated. RESULTS: After studying different factors, a fourfold increase in oral bioavailability was achieved with the non-PEGylated, 120-nm-sized positively charged rigid liposomes (lipid to drug ratio = 10). The extent of drug's first-pass metabolism as well as endocytosis of nanoparticles were markedly affected by liposomal formulation. CONCLUSION: Oral absorption is highly dependent on liposomal properties, and optimum formulations are effective for low-permeability drugs.