期刊
JOURNAL OF CONTROLLED RELEASE
卷 169, 期 1-2, 页码 10-16出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.03.037
关键词
Nanomedicines; Long-circulating nanocarriers; Nanocapsules; Polyglutamic acid; Cancer
资金
- CENIT-NANOFAR XS53 project, PharmaMar, Spain
- Ministry of Sciences and Innovation [CTQ2009-10963]
- Xunta de Galicia (Competitive Reference Groups-FEDER funds) [2010/18, CN2011/037]
- European Commission FP7 EraNet - EuroNanoMed Program-Instituto Carlos III [PS09/02670]
- Ministry of Education of Spain
- Isidro Parga Pondal Fellowship from Xunta de Galicia
A critical objective in cancer therapy is to reduce the systemic toxicity through the modification of the biodistribution of anticancer drugs. Herein, we disclose a new biodegradable nanocarrier, polyglutamic acid (PGA) nanocapsules, and present the in vivo pharmacokinetics/toxicity proof-of-concept for the anticancer drug plitidepsin. These novel nanocapsules were prepared using a modified solvent displacement technique where the polyamino acid was electrostatically deposited onto the lipid core. The nanocapsules exhibited an average size of 200 nm, a negative zeta potential and a great capacity for the encapsulation of plitidepsin (encapsulation efficiency above 90%). In addition, the nanocapsules could be freeze-dried and showed an adequate stability profile upon storage. Finally, the in vivo proof-of-concept studies performed in mice indicated that the encapsulation provided the drug with a prolonged blood circulation and a significantly reduced toxicity. In fact, the maximum tolerated dose of the nanoencapsulated drug was more than 3 times that of the reference formulation (Cremophor (R) EL plitidepsin solution). Overall, beyond the value of this specific formulation, the work reported here represents the evidence of the potential of polyamino acid nanocapsules in nano-oncological therapy. (C) 2013 Elsevier B.V. All rights reserved. NANOMEDICINE
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