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  • Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.

Tumor-targeted delivery of paclitaxel using low density lipoprotein-mimetic solid lipid nanoparticles.

Molecular pharmaceutics (2015-02-17)
Jin-Ho Kim, Youngwook Kim, Ki Hyun Bae, Tae Gwan Park, Jung Hee Lee, Keunchil Park
ABSTRACT

Water-insoluble anticancer drugs, including paclitaxel, present severe clinical side effects when administered to patients, primarily associated with the toxicity of reagents used to solubilize the drugs. In efforts to develop alternative formulations of water-insoluble anticancer drugs suitable for intravenous administration, we developed biocompatible anticancer therapeutic solid lipid nanoparticles (SLNs), mimicking the structure and composition of natural particles, low-density lipoproteins (LDLs), for tumor-targeted delivery of paclitaxel. These therapeutic nanoparticles contained water-insoluble paclitaxel in the core with tumor-targeting ligand covalently conjugated on the polyethylene glycol (PEG)-modified surface (targeted PtSLNs). In preclinical human cancer xenograft mouse model studies, the paclitaxel-containing tumor-targeting SLNs exhibited pronounced in vivo stability and enhanced biocompatibility. Furthermore, these SLNs had superior antitumor activity to in-class nanoparticular therapeutics in clinical use (Taxol and Genexol-PM) and yielded long-term complete responses. The in vivo targeted antitumor activities of the SLN formulations in a mouse tumor model suggest that LDL-mimetic SLN formulations can be utilized as a biocompatible, tumor-targeting platform for the delivery of various anticancer therapeutics.

MATERIALS
Product Number
Brand
Product Description

Supelco
Hydrogen chloride – 2-propanol solution, ~1.25 M HCl (T), for GC derivatization, LiChropur
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Glycine, tested according to Ph. Eur.
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Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
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Glycine, BioUltra, for molecular biology, ≥99.0% (NT)
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Glycine, analytical standard, for nitrogen determination according to Kjeldahl method
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Cholesterol solution, certified reference material, 10 mg/mL in chloroform
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Glycine, ACS reagent, ≥98.5%
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Cholesterol, tested according to Ph. Eur.
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Glycine, meets analytical specification of Ph. Eur., BP, USP, 99-101% (based on anhydrous substance)
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Glycine, 99%, FCC
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HEPES, BioUltra, for molecular biology, ≥99.5% (T)
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Glycine, ReagentPlus®, ≥99% (HPLC)
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Glycine, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, ≥98.5%
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Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
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L-α-Phosphatidylethanolamine, dioleoyl, ≥99% (GC), ≥98% (TLC), lyophilized powder
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Glycine, BioXtra, ≥99% (titration)
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Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
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Glyceryl trioleate, ≥99%
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HEPES, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
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HEPES, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
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HEPES, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
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Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
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Cholesterol, Sigma Grade, ≥99%
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Thiazolyl Blue Tetrazolium Bromide, 98%
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Glyceryl trioleate, ~65%
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Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
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Glycine, puriss. p.a., reag. Ph. Eur., buffer substance, 99.7-101% (calc. to the dried substance)
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2-Phenylindole, technical grade, 95%
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Cholesterol, from sheep wool, ≥92.5% (GC), powder
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Glycine, suitable for electrophoresis, ≥99%