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Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles.
Int J Pharm. 2012 Jul 01; 430(1-2):350-8.IJ

Abstract

To investigate the antitumor effect, biodistribution and penetration in tumors of docetaxel (DOC)-loaded polyethylene glycol-poly(caprolactone) (mPEG-PCL) nanoparticles on hepatic cancer model, DOC-loaded nanoparticles (DOC-NPs) were prepared with synthesized mPEG-PCL by nano-precipitated method with satisfactory encapsulation efficiency, loading capacity and size distribution. The fabricated nano-drugs were effectively transported into tumoral cells through endocytosis and localized around the nuclei in the cytoplasm. In vitro cytotoxicity test showed that DOC-NPs inhibited the murine hepatic carcinoma cell line H22 in a dose-dependent manner, which was similar to Taxotere, the commercialized formulation of docetaxel. The in vivo biodistribution performed on tumor-bearing mice by NIRF real-time imaging demonstrated that the nanoparticles achieved higher concentration and longer retention in tumors than in non-targeted organs after intravenous injection. The immunohistochemical analysis demonstrated that the nanoparticles located not only near the tumoral vasculatures, but also inside the tumoral interior. Therefore, DOC-NPs could penetrate into tumor parenchyma, leading to high intratumoral concentration of DOC. More importantly, the in vivo anti-tumor evaluation showed that DOC-NPs significantly inhibited tumor growth by tumor volume measurement and positron emission tomography and computed tomography (PET/CT) imaging observation. Taken together, the reported drug delivery system here could shed light on the future targeted therapy against hepatic carcinoma.

Authors+Show Affiliations

The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22525076

Citation

Liu, Qin, et al. "Enhanced Antitumor Efficacy, Biodistribution and Penetration of Docetaxel-loaded Biodegradable Nanoparticles." International Journal of Pharmaceutics, vol. 430, no. 1-2, 2012, pp. 350-8.
Liu Q, Li R, Zhu Z, et al. Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. Int J Pharm. 2012;430(1-2):350-8.
Liu, Q., Li, R., Zhu, Z., Qian, X., Guan, W., Yu, L., Yang, M., Jiang, X., & Liu, B. (2012). Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. International Journal of Pharmaceutics, 430(1-2), 350-8. https://doi.org/10.1016/j.ijpharm.2012.04.008
Liu Q, et al. Enhanced Antitumor Efficacy, Biodistribution and Penetration of Docetaxel-loaded Biodegradable Nanoparticles. Int J Pharm. 2012 Jul 1;430(1-2):350-8. PubMed PMID: 22525076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles. AU - Liu,Qin, AU - Li,Rutian, AU - Zhu,Zhenshu, AU - Qian,Xiaoping, AU - Guan,Wenxian, AU - Yu,Lixia, AU - Yang,Mi, AU - Jiang,Xiqun, AU - Liu,Baorui, Y1 - 2012/04/12/ PY - 2011/12/19/received PY - 2012/03/07/revised PY - 2012/04/05/accepted PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2012/9/29/medline SP - 350 EP - 8 JF - International journal of pharmaceutics JO - Int J Pharm VL - 430 IS - 1-2 N2 - To investigate the antitumor effect, biodistribution and penetration in tumors of docetaxel (DOC)-loaded polyethylene glycol-poly(caprolactone) (mPEG-PCL) nanoparticles on hepatic cancer model, DOC-loaded nanoparticles (DOC-NPs) were prepared with synthesized mPEG-PCL by nano-precipitated method with satisfactory encapsulation efficiency, loading capacity and size distribution. The fabricated nano-drugs were effectively transported into tumoral cells through endocytosis and localized around the nuclei in the cytoplasm. In vitro cytotoxicity test showed that DOC-NPs inhibited the murine hepatic carcinoma cell line H22 in a dose-dependent manner, which was similar to Taxotere, the commercialized formulation of docetaxel. The in vivo biodistribution performed on tumor-bearing mice by NIRF real-time imaging demonstrated that the nanoparticles achieved higher concentration and longer retention in tumors than in non-targeted organs after intravenous injection. The immunohistochemical analysis demonstrated that the nanoparticles located not only near the tumoral vasculatures, but also inside the tumoral interior. Therefore, DOC-NPs could penetrate into tumor parenchyma, leading to high intratumoral concentration of DOC. More importantly, the in vivo anti-tumor evaluation showed that DOC-NPs significantly inhibited tumor growth by tumor volume measurement and positron emission tomography and computed tomography (PET/CT) imaging observation. Taken together, the reported drug delivery system here could shed light on the future targeted therapy against hepatic carcinoma. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/22525076/Enhanced_antitumor_efficacy_biodistribution_and_penetration_of_docetaxel_loaded_biodegradable_nanoparticles_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(12)00354-7 DB - PRIME DP - Unbound Medicine ER -