title: Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.
abstract: The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: James
authors.initials: J
authors.lastname: Liu
authors.forename: Benjawan
authors.initials: B
authors.lastname: Boonkaew
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Arora
authors.forename: Sree Harsha
authors.initials: SH
authors.lastname: Mandava
authors.forename: Michael M
authors.initials: MM
authors.lastname: Maddox
authors.forename: Srinivas
authors.initials: S
authors.lastname: Chava
authors.forename: Cameron
authors.initials: C
authors.lastname: Callaghan
authors.forename: Jibao
authors.initials: J
authors.lastname: He
authors.forename: Srikanta
authors.initials: S
authors.lastname: Dash
authors.forename: Vijay T
authors.initials: VT
authors.lastname: John
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Lee
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008081:Liposomes; D053758:Nanoparticles; D036103:Nanotechnology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D000077157:Sorafenib; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010671:Phenylurea Compounds; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D009536:Niacinamide; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D019344:Lactic Acid; D048271:Chitosan; D000077157:Sorafenib
keywords: cancer chemotherapy; chitosan; drug transport; liposomes; nanotechnology; poly (lactic/glycolic) acid (PLGA)