title: Release kinetics of paclitaxel and cisplatin from two and three layered gold nanoparticles.
abstract: Gold nanoparticles functionalized with biologically compatible layers may achieve stable drug release while avoiding adverse effects in cancer treatment. We study cisplatin and paclitaxel release from gold cores functionalized with hexadecanethiol (TL) and phosphatidylcholine (PC) to form two-layer nanoparticles, or TL, PC, and high density lipoprotein (HDL) to form three-layer nanoparticles. Drug release was monitored for 14 days to assess long term effects of the core surface modifications on release kinetics. Release profiles were fitted to previously developed kinetic models to differentiate possible release mechanisms. The hydrophilic drug (cisplatin) showed an initial (5-h) burst, followed by a steady release over 14 days. The hydrophobic drug (paclitaxel) showed a steady release over the same time period. Two layer nanoparticles released 64.0±2.5% of cisplatin and 22.3±1.5% of paclitaxel, while three layer nanoparticles released the entire encapsulated drug. The Korsmeyer-Peppas model best described each release scenario, while the simplified Higuchi model also adequately described paclitaxel release from the two layer formulation. We conclude that functionalization of gold nanoparticles with a combination of TL and PC may help to modulate both hydrophilic and hydrophobic drug release kinetics, while the addition of HDL may enhance long term release of hydrophobic drug.
authors.affiliation: Dept. of Pharmacology & Toxicology, University of Louisville, KY, USA; James Graham Brown Cancer Center, University of Louisville, KY, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: England
authors.affiliation: Dept. of Chemistry/Biochemistry, University of North Georgia, GA, USA.
authors.forename: M Clarke
authors.initials: MC
authors.lastname: Miller
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, KY, USA; Dept. of Medicine, University of Louisville, KY, USA.
authors.forename: Ashani
authors.initials: A
authors.lastname: Kuttan
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, KY, USA; Dept. of Medicine, University of Louisville, KY, USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Trent
authors.affiliation: Dept. of Pharmacology & Toxicology, University of Louisville, KY, USA; James Graham Brown Cancer Center, University of Louisville, KY, USA; Dept. of Bioengineering, University of Louisville, KY, USA. Electronic address: hbfrie01@louisville.edu.
authors.forename: Hermann B
authors.initials: HB
authors.lastname: Frieboes
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D006046:Gold / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry; D053768:Metal Nanoparticles; D008956:Models, Chemical; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D013438:Sulfhydryl Compounds; C086974:hexadecanethiol; D006046:Gold; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cisplatin; Drug release kinetics; Drug release modeling; Nanotherapy; Paclitaxel