Targeted delivery of platinum-taxane combination therapy in ovarian cancer

Swapnil S. Desale, Kruti S. Soni, Svetlana Romanova, Samuel Monroe Cohen, Tatiana K Bronich

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Biodegradable polypeptide-based nanogels have been developed from amphiphilic block copolymers, poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l-phenylalanine), which effectively co-incorporate cisplatin and paclitaxel, the clinically used drug combination for the treatment of advanced ovarian cancer. In order to target both drugs selectively to the tumor cells, we explored the benefits of ligand-mediated drug delivery by targeting folate receptors, which are overexpressed in most ovarian cancers. Drug-loaded nanogels were surface-functionalized with folic acid (FA) with the help of a PEG spacer without affecting the ligand binding affinity and maintaining the stability of the carrier system. FA-decorated nanogels significantly suppressed the growth of intraperitoneal ovarian tumor xenografts outperforming their nontargeted counterparts without extending their cytotoxicity to the normal tissues. We also confirmed that synchronized co-delivery of the platinum-taxane drug combination via single carrier to the same targeted cells is more advantageous than a combination of targeted single drug formulations administered at the same drug ratio. Lastly, we demonstrated that the same platform can also be used for localized chemotherapy. Our data indicate that intraperitoneal administration can be more effective in the context of targeted combination therapy. Our findings suggest that multifunctional nanogels are promising drug delivery carriers for improvement of current treatment for ovarian cancer.

Original languageEnglish (US)
Pages (from-to)651-659
Number of pages9
JournalJournal of Controlled Release
Volume220
DOIs
StatePublished - Dec 28 2015

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Keywords

  • Cisplatin
  • Combination drug delivery
  • Nanogels
  • Ovarian cancer
  • Paclitaxel
  • Receptor targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

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