title: Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric nanoparticles for breast cancer.
abstract: Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino-17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90 (HSP90). Folate targeted polylactide-co-glycolide-polyethylene glycol-folic acid (PLGA-PEG-FA) nanoparticles containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded folate targeted nanoparticles was 238.67±3.52 nm, drug loading was 8.25±2.49% and about 80% of drug was released from the nanoparticles over 10 days. Cellular uptake studies showed much higher intracellular uptake of folate targeted nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed 2 fold increase (P<0.05, n=3) in the cytotoxicity of folate targeted nanoparticle in comparison to free drug or nontargeted nanoparticles. Due to their targeting ability, nanometer size, high drug loading and controlled release behavior, 17-AAG loaded PLGA-PEG-FA nanoparticles might be developed as a targeted delivery system for breast and other cancer treatment.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Saxena
authors.forename: Youssef
authors.initials: Y
authors.lastname: Naguib
authors.forename: M Delwar
authors.initials: MD
authors.lastname: Hussain
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D016227:Benzoquinones / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000737:chemistry / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D047029:Lactams, Macrocyclic / Q000008:administration & dosage* / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D047029:Lactams, Macrocyclic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C112765:tanespimycin; D005492:Folic Acid