| Autor: |
Amoozgar Z; Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute , Boston, Massachusetts 02215, United States., Wang L, Brandstoetter T, Wallis SS, Wilson EM, Goldberg MS |
| Jazyk: |
angličtina |
| Zdroj: |
Biomacromolecules [Biomacromolecules] 2014 Nov 10; Vol. 15 (11), pp. 4187-94. Date of Electronic Publication: 2014 Oct 07. |
| DOI: |
10.1021/bm5011933 |
| Abstrakt: |
Development of drug resistance is a central challenge to the treatment of ovarian cancer. Metronomic chemotherapy decreases the extent of drug-free periods, thereby hindering development of drug resistance. Intraperitoneal chemotherapy allows for treatment of tumors confined within the peritoneum, but achieving sustained tumor-localized chemotherapy remains difficult. We hypothesized that modulating the surface properties of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles could enhance their drug retention ability and extend their release profile, thereby enabling metronomic, localized chemotherapy in vivo. Paclitaxel was encapsulated in particles coated with a layer of polydopamine and a subsequent layer of poly(ethylene glycol) (PEG). These particles achieved a 3.8-fold higher loading content compared to that of nanoparticles formulated from linear PLGA-PEG copolymers. In vitro release kinetic studies and in vivo drug distribution profiles demonstrate sustained release of paclitaxel. Although free drug conferred no survival advantage, low-dose intraperitoneal administration of paclitaxel-laden surface-coated nanoparticles to drug-resistant ovarian tumor-bearing mice resulted in significant survival benefits in the absence of any apparent systemic toxicity. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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