title: Targeted albumin-based nanoparticles for delivery of amphipathic drugs.
abstract: We report the preparation and physical and biological characterization of human serum albumin-based micelles of approximately 30 nm diameter for the delivery of amphipathic drugs, represented by doxorubicin. The micelles were surface conjugated with cyclic RGD peptides to guide selective delivery to cells expressing the α(v)β(3) integrin. Multiple poly(ethylene glycol)s (PEGs) with molecular weight of 3400 Da were used to form a hydrophilic outer layer, with the inner core formed by albumin conjugated with doxorubicin via disulfide bonds. Additional doxorubicin was physically adsorbed into this core to attain a high drug loading capacity, where each albumin was associated with about 50 doxorubicin molecules. The formed micelles were stable in serum but continuously released doxorubicin when incubated with free thiols at concentrations mimicking the intracellular environment. When incubated with human melanoma cells (M21+) that express the α(v)β(3) integrin, higher uptake and longer retention of doxorubicin was observed with the RGD-targeted micelles than in the case of untargeted control micelles or free doxorubicin. Consequently, the RGD-targeted micelles manifested cytotoxicity at lower doses of drug than control micelles or free drug.
authors: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, United States.
authors: Rongzuo
authors: R
authors: Xu
authors: Michael
authors: M
authors: Fisher
authors: R L
authors: RL
authors: Juliano
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D008823:Micelles; D010456:Peptides, Cyclic; D012709:Serum Albumin; C507169:cyclic arginine-glycine-aspartic acid peptide; D011092:Polyethylene Glycols; D004317:Doxorubicin