title: Porous quaternized chitosan nanoparticles containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer after oral administration.
abstract: Clinical application of paclitaxel (PTX) is limited because of its poor solubility in aqueous media. To overcome this hurdle, we devised an oral delivery system by encapsulating PTX into N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles. These nanoparticles were small (~130 nm), had a narrow size distribution, and displayed high loading efficiency owing to the homogeneous distribution of PTX nanocrystals. The matrix hydrophilicity and porous structure of the obtained nanoparticles accelerated their degradation and improved drug release. In vitro and in vivo transport experiments had proved that the presence of positive charges enhanced the intestinal permeability of these nanoparticles. Further in vitro experiment of cytotoxicity showed that the PTX-loaded HTCC nanoparticle (HTCC-NP:PTX) was more effective than native PTX owing to enhanced cellular uptake. Drug distribution in tissues and in vivo imaging studies confirmed the preferred accumulation of HTCC-NP:PTX in subcutaneous tumor tissue. Subsequent tumor xenograft assays demonstrated the promising therapeutic effect of HTCC-NP:PTX on inhibition of tumor growth and induction of apoptosis in tumor cells. Additional investigation into side effects revealed that HTCC-NP:PTX caused lower Cremophor EL-associated toxicities compared with Taxol. These results strongly supported the notion that HTCC nanoparticle (HTCC-NP) is a promising candidate as an oral carrier of PTX for cancer therapy.
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P R China.
authors: Pi-Ping
authors: PP
authors: Lv
authors: Wei
authors: W
authors: Wei
authors: Hua
authors: H
authors: Yue
authors: Ting-Yuan
authors: TY
authors: Yang
authors: Lian-Yan
authors: LY
authors: Wang
authors: Guang-Hui
authors: GH
authors: Ma
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; C550160:N-(2-hydroxypropyl)-3-trimethylammonium chitosan; D000644:Quaternary Ammonium Compounds; D048271:Chitosan; D017239:Paclitaxel