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Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo.
Int J Pharm 2014; 471(1-2):525-35IJ

Abstract

Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer prodrug because of its poor antitumor efficiency. But surprisingly, it was found in our study that PEG-PTX could form a novel nanoparticle system with free PTX. To address how this system works, we compared PTX loaded PEG-PTX nanoparticles (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection available (Taxol(®)) in vitro and in vivo. Firstly, it was found that PEG-PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX crystal formation and drug release. Then it was demonstrated that coumarin loaded PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG-PLA micelles and solvent system of Taxol(®). In the efficacy study with MCF-7 tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity than PEG-PLA/PTX at the same PTX dosage. At the dose of 10mg free PTX per kg, PEG-PTX/PTX displayed similar efficacy as Taxol(®) but less toxicity evaluated by the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX showed significantly better efficacy than Taxol(®). In conclusion, with favorable characteristics in stability, cellular uptake, cytotoxicity, biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a nanocarrier for PTX delivery.

Authors+Show Affiliations

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: wangxq@bjmu.edu.cn.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: zqdodo@bjmu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

24858391

Citation

Lu, Jingkai, et al. "Free Paclitaxel Loaded PEGylated-paclitaxel Nanoparticles: Preparation and Comparison With Other Paclitaxel Systems in Vitro and in Vivo." International Journal of Pharmaceutics, vol. 471, no. 1-2, 2014, pp. 525-35.
Lu J, Chuan X, Zhang H, et al. Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo. Int J Pharm. 2014;471(1-2):525-35.
Lu, J., Chuan, X., Zhang, H., Dai, W., Wang, X., Wang, X., & Zhang, Q. (2014). Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo. International Journal of Pharmaceutics, 471(1-2), pp. 525-35. doi:10.1016/j.ijpharm.2014.05.032.
Lu J, et al. Free Paclitaxel Loaded PEGylated-paclitaxel Nanoparticles: Preparation and Comparison With Other Paclitaxel Systems in Vitro and in Vivo. Int J Pharm. 2014 Aug 25;471(1-2):525-35. PubMed PMID: 24858391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Free paclitaxel loaded PEGylated-paclitaxel nanoparticles: preparation and comparison with other paclitaxel systems in vitro and in vivo. AU - Lu,Jingkai, AU - Chuan,Xingxing, AU - Zhang,Hua, AU - Dai,Wenbing, AU - Wang,Xinglin, AU - Wang,Xueqing, AU - Zhang,Qiang, Y1 - 2014/05/22/ PY - 2014/02/18/received PY - 2014/05/01/revised PY - 2014/05/18/accepted PY - 2014/5/27/entrez PY - 2014/5/27/pubmed PY - 2015/2/20/medline KW - Antitumor effect KW - Nanoparticles KW - PEG-PLA KW - PEGylated paclitaxel KW - Paclitaxel KW - Taxol SP - 525 EP - 35 JF - International journal of pharmaceutics JO - Int J Pharm VL - 471 IS - 1-2 N2 - Previously, PEGylated paclitaxel (PEG-PTX) was found not favorable as a polymer prodrug because of its poor antitumor efficiency. But surprisingly, it was found in our study that PEG-PTX could form a novel nanoparticle system with free PTX. To address how this system works, we compared PTX loaded PEG-PTX nanoparticles (PEG-PTX/PTX) with PTX loaded PEG-PLA micelles (PEG-PLA/PTX) or PTX injection available (Taxol(®)) in vitro and in vivo. Firstly, it was found that PEG-PTX/PTX was more stable in aqueous solution than PEG-PLA/PTX in terms of PTX crystal formation and drug release. Then it was demonstrated that coumarin loaded PEG-PTX nanoparticles had a much higher uptake in MCF-7 cells compared to coumarin loaded PEG-PLA micelles. The in vivo imaging study revealed that DIR or DID (near infrared fluorescent substances) loaded PEG-PTX nanoparticles distributed more in tumors in MCF-7 tumor bearing mice than DIR or DID loaded PEG-PLA micelles and solvent system of Taxol(®). In the efficacy study with MCF-7 tumor bearing mice, PEG-PTX/PTX showed significantly higher antitumor activity than PEG-PLA/PTX at the same PTX dosage. At the dose of 10mg free PTX per kg, PEG-PTX/PTX displayed similar efficacy as Taxol(®) but less toxicity evaluated by the loss of body weight. With the increase of free PTX to 15 mg/kg, PEG-PTX/PTX showed significantly better efficacy than Taxol(®). In conclusion, with favorable characteristics in stability, cellular uptake, cytotoxicity, biodistribution, safety and efficacy, PEG-PTX/PTX seems highly potential as a nanocarrier for PTX delivery. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/24858391/Free_paclitaxel_loaded_PEGylated_paclitaxel_nanoparticles:_preparation_and_comparison_with_other_paclitaxel_systems_in_vitro_and_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(14)00372-X DB - PRIME DP - Unbound Medicine ER -