Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles

• Published in: Archives of pharmacal research 2015, 38(5), , pp.734-741
• Main Authors: Pradhan, Roshan, Poudel, Bijay Kumar, Choi, Ju Yeon, Choi, Im Soon, Shin, Beom Soo, Choi, Han-Gon, Yong, Chul Soon, Kim, Jong Oh
• Format: Article
• Language: English
• Subjects: Benzoquinones - administration & dosage; Benzoquinones - chemical synthesis; Benzoquinones - metabolism; Cell Survival - drug effects; Cell Survival - physiology; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Humans; Lactams, Macrocyclic - administration & dosage; Lactams, Macrocyclic - chemical synthesis; Lactams, Macrocyclic - metabolism; Lactic Acid - administration & dosage; Lactic Acid - chemical synthesis; Lactic Acid - metabolism; MCF-7 Cells; Medicine; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - metabolism; Particle Size; Pharmacology/Toxicology; Pharmacy; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemical synthesis; Polyglycolic Acid - metabolism; Research Article; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-014-0404-7

In the present study, we developed the novel 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid- co -glycolic acid) (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate and poloxamer 407 as the anionic and non-ionic surfactant for stabilization. The PLGA NPs were prepared by emulsification/solvent evaporation method. Both the drug/polymer ratio and phase ratio were 1:10 (w/w). The optimized formulation of 17-AAG-loaded PLGA NPs had a particle size and polydispersity index of 151.6 ± 2.0 and 0.152 ± 0.010 nm, respectively, which was further supported by TEM image. The encapsulation efficiency and drug loading capacity were 69.9 and 7.0 %, respectively. In vitro release study showed sustained release. When in vitro release data were fitted to Korsmeyer–Peppas model, the n value was 0.468, which suggested that the drug was released by anomalous or non-Fickian diffusion. In addition, 17-AAG-loaded PLGA NPs in 72 h, displayed approximately 60 % cell viability reduction at 10 µg/ml 17-AAG concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of 17-AAG into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.