title: Development of docetaxel nanocrystals surface modified with transferrin for tumor targeting.
abstract: The purpose of this study was to develop the surface modification of docetaxel nanocrystals (DTX-NCs) with apo-Transferrin human (Tf) for improving the cellular uptake and cytotoxicity of DTX. DTX-NCs were prepared by a nanoprecipitation method, and the surface modified with Tf by an adsorption method (Tf-DTX-NCs). The morphology and particle size of DTX-NCs and Tf-DTX-NCs were characterized using a field emission scanning electron microscope and zetasizer. An in vitro drug release study was performed in phosphate-buffered saline containing 0.5% (w/v) Tween 80 for 24 hours. Cellular uptake was studied at 0.5, 1, and 2 hours. A cytotoxicity study was performed using the A549 (human lung cancer) cell line after 24-, 48-, and 72-hour treatments. The mean sizes were 295±97 and 398±102 nm for DTX-NCs and Tf-DTX-NCs, respectively. Tf-DTX-NCs and DTX-NCs exhibited rapid drug release, whereas DTX (pure) was slowly released. Tf-DTX-NCs showed higher cellular uptake than DTX-NCs in confocal microscopic and quantitative studies. Moreover, at DTX concentration of 100 µg/mL, Tf-DTX-NCs (82.6%±0.8%) showed higher cytotoxicity than DTX-NCs (77.4%±4.1%) and DTX (pure; 20.1%±4.6%) for 72-hour treatment. In conclusion, Tf-DTX-NCs significantly improved the cellular uptake and cytotoxicity of DTX in the A549 cell line.
authors.affiliation: College of Pharmacy, Institute of Drug Research and Development, Chungnam National University, Yuseong-gu, Daejeon, South Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Institute of Drug Research and Development, Chungnam National University, Yuseong-gu, Daejeon, South Korea.
authors.forename: Jeong-Sook
authors.initials: JS
authors.lastname: Park
mesh_terms: D000327:Adsorption; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D014168:Transferrin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D014168:Transferrin; D000077143:Docetaxel
keywords: apo-Transferrin human; docetaxel; nanocrystals; surface modification