Improved i.p. drug delivery with bioadhesive nanoparticles

Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11453-11458. doi: 10.1073/pnas.1523141113. Epub 2016 Sep 23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adhesives / administration & dosage*
  • Animals
  • Cell Proliferation / drug effects
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / pathology
  • Drug Delivery Systems*
  • Epothilones / administration & dosage
  • Epothilones / pharmacology
  • Epothilones / therapeutic use
  • Female
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Injections, Intraperitoneal
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / pathology

Substances

  • Adhesives
  • Epothilones
  • epothilone B