Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

Jong Oh Kim, Hardeep S. Oberoi, Swapnil Desale, Alexander V. Kabanov, Tatiana K. Bronich

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(l-glutamic acid), hydrophobically modified with l-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)981-993
Number of pages13
JournalJournal of Drug Targeting
Volume21
Issue number10
DOIs
StatePublished - Dec 2013

Keywords

  • Core-shell morphology
  • Doxorubicin
  • Nanogel
  • PEG-b-poly(l-glutamic acid)
  • Phenylalanine

ASJC Scopus subject areas

  • Pharmaceutical Science

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