title: Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin.
abstract: Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3±2.2nm), polydispersity index (0.151±0.026), and zeta potential (-12.4±0.4mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Roshan
authors.initials: R
authors.lastname: Pradhan
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Poudel
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Tak
authors.affiliation: Department of Fundamental and Applied Neurobiology, Serbsky National Research Center for Social and Forensic Psychiatry, Moscow, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Nukolova
authors.affiliation: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea. Electronic address: hangon@hanyang.ac.kr.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea. Electronic address: csyong@yu.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D016227:Benzoquinones / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D014183:Transplantation, Heterologous; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D004337:Drug Carriers; D004655:Emulsions; D047029:Lactams, Macrocyclic; D009821:Oils; D043823:Taxoids; D014867:Water; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C112765:tanespimycin; D006820:Hyaluronic Acid
keywords: Combined therapy; Docetaxel; Poly(lactic-co-glycolic acid); Synergic effect; Tanespimycin