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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

SAFC
Cholesterol, Plant-Derived, SyntheChol®
Sigma-Aldrich
3-(4-Hydroxyphenyl)propionic acid N-hydroxysuccinimide ester, suitable for fluorescence, BioReagent, ≥97.0% (C)
Sigma-Aldrich
Hydrogen chloride, ReagentPlus®, ≥99%
Sigma-Aldrich
Cholesteryl oleate, ≥98% (HPLC; detection at 205 nm)
Sigma-Aldrich
3-(4-Hydroxyphenyl)propionic acid N-hydroxysuccinimide ester, ~90%
Paclitaxel, European Pharmacopoeia (EP) Reference Standard
Paclitaxel semi-synthetic for system suitability, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
N-Hydroxysuccinimide, 98%
Sigma-Aldrich
N-Hydroxysuccinimide, purum, ≥97.0% (T)
Sigma-Aldrich
Fluorescamine, ≥98% (TLC), powder, used for detection of primary amines
Sigma-Aldrich
HEPES buffer solution, 1 M in H2O
Sigma-Aldrich
Paclitaxel, from Taxus yannanensis, powder
Sigma-Aldrich
Paclitaxel, from Taxus brevifolia, ≥95% (HPLC), powder
Sigma-Aldrich
Paclitaxel, from semisynthetic, ≥98%
Paclitaxel natural for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Glycine, analytical standard, for nitrogen determination according to Kjeldahl method
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
Supelco
Glycine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
Supelco
Cholesterol solution, certified reference material, 10 mg/mL in chloroform
Paclitaxel semi-synthetic for peak identification, European Pharmacopoeia (EP) Reference Standard
SAFC
HEPES
Supelco
Glycine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Glyceryl trioleate, ≥97.0% (TLC)
Sigma-Aldrich
Cholesterol, tested according to Ph. Eur.
Sigma-Aldrich
Cholesterol, from lanolin, ≥99.0% (GC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
Sigma-Aldrich
L-α-Phosphatidylethanolamine, dioleoyl, ≥99% (GC), ≥98% (TLC), lyophilized powder