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  3. School of Dentistry / 牙醫專業學院
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  5. Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications than bioequivalent doses of Taxol
 
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Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications than bioequivalent doses of Taxol

Journal
International Journal of Oncology
Journal Volume
53
Journal Issue
3
Pages
1105-1117
Date Issued
2018
Author(s)
Huang S.-T.
YI-PING WANG  
Chen Y.-H.
CHIN-TARNG LIN  
Li W.-S.
Wu H.-C.
DOI
10.3892/ijo.2018.4449
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052013784&doi=10.3892%2fijo.2018.4449&partnerID=40&md5=202465c785ec94a17dbd47a94c7843b1
https://scholars.lib.ntu.edu.tw/handle/123456789/570225
Abstract
Paclitaxel (PTX) exhibits potent antineoplastic activity against various human malignancies; however, clinical application must overcome the inherent hydrophobicity of this molecule. The commercialized Taxol formulation utilizes Cremophor EL (CrEL)/ethanol as a solvent to stabilize and dispense PTX in an aqueous solution. However, adverse CrEL-induced hypersensitivity reactions have been reported in ~30% of recipients, and 40% of patients receiving premedication may also experience this adverse effect. Therefore, the development of a CrEL-free delivery system is crucial, in order to fully exploit the therapeutic efficacy of PTX. In the present study, a novel liposomal PTX (lipo-PTX) formulation was optimized with regards to encapsulation rate and long-term stability, arriving at a molar constituent ratio of soybean phosp hatidylcholine:cholesterol:N-(carbonyl-methoxy-poly-ethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanol-amine, sodium salt:PTX at 95:2:1:2. Comparable doses of lipo-PTX and Taxol were bioequivalent in terms of therapeutic efficacy in xenograft tumor models. However, the systemic side effects, including hematopoietic toxicity, acute hypersensitivity reactions and cardiac irregularities, were significantly reduced in lipo-PTX-treated mice compared with those infused with reference formulations of PTX. In conclusion, the present study reported that lipo-PTX exhibited a higher therapeutic index than clinical PTX formulations. ? 2018 Spandidos Publications. All Rights Reserved.
SDGs

[SDGs]SDG3

Other Subjects
liposome; n (carbonyl methoxy poly ethylene); paclitaxel; phosphatidylcholine; polyethylene; soybean phosphatidylcholine; unclassified drug; antineoplastic agent; cremophor; drug carrier; glycerol; liposome; paclitaxel; allergic reaction; animal cell; animal experiment; animal tissue; antineoplastic activity; Article; bioequivalence; cardiovascular disease; controlled study; drug bioavailability; drug delivery system; drug efficacy; drug formulation; drug stability; encapsulation; female; human; human cell; in vitro study; in vivo study; lymphatic system disease; mouse; nonhuman; particle size; physical chemistry; priority journal; process optimization; therapeutic index; tumor xenograft; analogs and derivatives; animal; cardiovascular disease; cell survival; chemically induced; chemistry; drug effect; drug release; drug screening; hematologic disease; Institute for Cancer Research mouse; male; neutropenia; procedures; SCID mouse; therapeutic equivalence; tissue distribution; tumor cell line; Animals; Antineoplastic Agents, Phytogenic; Cardiovascular Diseases; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Compounding; Drug Liberation; Drug Screening Assays, Antitumor; Female; Glycerol; Hematologic Diseases; Humans; Liposomes; Male; Mice; Mice, Inbred ICR; Mice, SCID; Neutropenia; Paclitaxel; Therapeutic Equivalency; Tissue Distribution
Publisher
Spandidos Publications
Type
journal article

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