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Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11453-11458. Epub 2016 Sep 23.

Improved i.p. drug delivery with bioadhesive nanoparticles.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT 06511.
2
Department of Obstetrics, Gynecology & Reproductive Sciences, School of Medicine, Yale University, New Haven, CT 06511.
3
Department of Biomedical Engineering, Yale University, New Haven, CT 06511; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT 06511.
4
Department of Biomedical Engineering, Yale University, New Haven, CT 06511; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT 06511 mark.saltzman@yale.edu.

Abstract

The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB.

KEYWORDS:

chemotherapy; drug delivery; intraperitoneal; nanoparticles; ovarian cancer

PMID:
27663731
PMCID:
PMC5068292
DOI:
10.1073/pnas.1523141113
[Indexed for MEDLINE]
Free PMC Article

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