title: Biochemically altered human erythrocytes as a carrier for targeted delivery of primaquine: an in vitro study.
abstract: The aim of this study was to investigate human erythrocytes as a carrier for targeted drug delivery of primaquine (PQ). The process of PQ loading in human erythrocytes, as well as the effect of PQ loading on the oxidative status of erythrocytes, was also studied. At PQ concentrations of 2, 4, 6, and 8 mg/mL and an incubation time of 2 h, the ratios of the concentrations of PQ entrapped in erythrocytes to that in the incubation medium were 0.515, 0.688, 0.697 and 0.788, respectively. The maximal decline of erythrocyte reduced glutathione content was observed at 8 mg/mL of PQ compared with native erythrocytes p < 0.001. In contrast, malondialdehyde and protein carbonyl were significantly increased in cells loaded with PQ (p < 0.001). Furthermore, osmotic fragility of PQ carrier erythrocytes was increased in comparison with unloaded cells. Electron microscopy revealed spherocyte formation with PQ carrier erythrocytes. PQ-loaded cells showed sustained drug release over a 48 h period. Erythrocytes were loaded with PQ successfully, but there were some biochemical as well as physiological changes that resulted from the effect of PQ on the oxidative status of drug-loaded erythrocytes. These changes may result in favorable targeting of PQ-loaded cells to reticulo-endothelial organs. The relative impact of these changes remains to be explored in ongoing animal studies.
authors.affiliation: College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Fars K
authors.initials: FK
authors.lastname: Alanazi
authors.forename: Gamal El-Din I
authors.initials: Gel-D
authors.lastname: Harisa
authors.forename: Ahmad
authors.initials: A
authors.lastname: Maqboul
authors.forename: Magdi
authors.initials: M
authors.lastname: Abdel-Hamid
authors.forename: Steven H
authors.initials: SH
authors.lastname: Neau
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alsarra
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009996:Osmotic Fragility; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011319:Primaquine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D050050:Protein Carbonylation; D013499:Surface Properties
chemical_list: D000962:Antimalarials; D004337:Drug Carriers; D006454:Hemoglobins; D008315:Malondialdehyde; D005978:Glutathione; D011319:Primaquine