Details

Autor(en) / Beteiligte

• Yang, Rui
• Yang, Su-Geun
• Shim, Won-Sik
• Cui, Fude
• Cheng, Gang
• Kim, In-Wha
• Kim, Dae-Duk
• Chung, Suk-Jae
• Shim, Chang-Koo

Titel

Lung-Specific Delivery of Paclitaxel by Chitosan-Modified PLGA Nanoparticles Via Transient Formation of Microaggregates

Ist Teil von

• Journal of pharmaceutical sciences, 2009-03, Vol.98 (3), p.970-984

Ort / Verlag

Hoboken: Elsevier Inc

Erscheinungsjahr

2009

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Chitosan-modified paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles with a mean diameter of 200–300nm in distilled water were prepared by a solvent evaporation method. The mean diameter increased dramatically in contact with the mouse (CDF1) plasma, as a function of chitosan concentration in the modification solution (e.g., 2670.5nm for 0.7% chitosan-modified nanoparticles, NP3), but reverted to almost its original size (i.e., 350.7nm for NP3) following 5min of gentle agitation. The zeta potential of PLGA nanoparticles was changed to positive by the chitosan modification. The in vitro uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell line (A549) were significantly increased by the modification. Most importantly, a lung-specific increase in the distribution index of paclitaxel (i.e., AUClung/AUCplasma) was observed for chitosan-modified nanoparticles (e.g., 99.9 for NP3 vs. 5.4 for Taxol™) when nanoparticles were administered to lung-metastasized mice via the tail vein at a paclitaxel dose of 10mg/kg. Transient formation of aggregates in the blood stream followed by enhanced trapping in the lung capillaries, and electrical interaction-mediated enhanced uptake across the endothelial cells of the lung tumor capillary appear to be responsible for the lung-tumor-specific distribution of the chitosan modified nanoparticles.