Polymer nanoparticles encased in a cyclodextrin complex shell for potential site- and sequence-specific drug release

Guillermo U. Ruiz-Esparza, Suhong Wu, Victor Segura-Ibarra, Francisca E. Cara, Kurt W. Evans, Miljan Milosevic, Arturas Ziemys, Milos Kojic, Funda Meric-Bernstam, Mauro Ferrari, Elvin Blanco

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Time-staggered combination chemotherapy strategies show immense potential in cell culture systems, but fail to successfully translate clinically due to different routes of administration and disparate formulation parameters that preclude a specific order of drug presentation. A novel platform consisting of drug-containing PLGA polymer nanoparticles, stably fashioned with a shell composed of drug complexed with cationic cyclodextrin, capable of releasing drugs time- and sequence-specifically within tumors is designed. Morphological examination of nanoparticles measuring 150 nm highlight stable and distinct compartmentalization of model drugs, rhodamine and bodipy, within the core and shell, respectively. Sequential release is observed in vitro, owing to cyclodextrin shell displacement and subsequent sustained release of core-loaded drug, kinetics preserved in breast cancer cells following internalization. Importantly, time-staggered release is corroborated in a murine breast cancer model following intravenous administration. Precise control of drug release order, site-specifically, potentially opens novel avenues in polychemotherapy for synergy and chemosensitization strategies. A nanoplatform consisting of drug-containing PLGA polymer nanoparticles, stably fashioned with a shell composed of drug complexed with cationic cyclodextrin, enables drug release in a time- and sequence-specific manner within tumors for synergy enhancement. Sequential release in both the in vitro and in vivo setting, site-specifically, highlights the potential to translate time-staggered combination chemotherapy strategies to the clinical arena.

Original languageEnglish (US)
Pages (from-to)4753-4761
Number of pages9
JournalAdvanced Functional Materials
Volume24
Issue number30
DOIs
StatePublished - Aug 13 2014

Keywords

  • breast cancer
  • cyclodextrins
  • nanoparticle-based drug delivery
  • poly(lactic-co-glycolic acid) (PLGA)
  • sequential release

ASJC Scopus subject areas

  • Biomaterials
  • Electrochemistry
  • Condensed Matter Physics
  • Electronic, Optical and Magnetic Materials

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