Journal of Developing Drugs
Open Access
ISSN: 2329-6631
+44 1478 350008
ISSN: 2329-6631
+44 1478 350008
Mahasen Ali Radwan, B T AlQuadeib, L Siller, M Wright and B Horrocks
Princess Nourah University, Saudi Arabia
King Saud University, Saudi Arabia
Newcastle University, UK
Posters & Accepted Abstracts: J Develop Drugs
Amphotericin B (AMB) is the gold standard treatment of systemic fungal infections. However, the only available dosage form of AMB is the parenteral formulations. Oral delivery for AMB is the utmost invention to overcome its adverse effects and nephrotoxicity for better patient adherence and minimal hospitalization time. Therefore, a novel delivery for AMB loaded to PEGylated polylactic-polyglycolic (PLGA-PEG) nanoparticles (NPs) was developed. The feasibility of the developed system in rats with and without an absorption enhancer, glycyrrhizic acid (GA) as well as the in vitro efficacy and in vivo toxicity of these formulations were the aim of this investigation. The absolute and relative bioavailabilities of AMB selected formulations (F1 and F2) were conducted in nine groups of rats (n=6), using Fungizone�?® as reference standard. Plasma concentrations were measured using a developed sensitive and precise LC/MS/MS assay. The toxicity of AMB in these formulations was examined by in vitro blood hemolysis test and the in vivo nephrotoxicity was carried out in five groups of rats (n=3) dosed daily as 5.0 mg/kg via iv after single and multiple dosing for a week by measuring the blood urea nitrogen (BUN) and plasma creatinine (PCr). The in vitro AMB antifungal activity of these formulations on C. albicans was also assessed. Oral administration of AMB loaded to PLGA-PEG NPs to rats resulted in considerable oral absorption compared to Fungizone�?® administered orally (63.8%). The addition of GA significantly (P<0.05) increases AmB Cmax (2 - 3 folds). There was no significant change (P=0.09) in adding GA during formulation or just before administration. The addition of 2% of GA to AMB formulation significantly (P<0.05) improved its bioavailability by 10.5% and the relative bioavailability was >790%. The developed AMB formulations show minimal toxicity and better efficacy compared to Fungizone�?®. No nephrotoxicity, in rats, was developed after a week of multiple dosing of AMB NPs as the BUN and PCr were within the normal levels.
Email: maradwan@pnu.edu.sa