Nanodiamond-insulin complexes as pH-dependent protein delivery vehicles

Rafael A. Shimkunas, Erik Robinson, Robert Lam, Steven Lu, Xiaoyang Xu, Xue Qing Zhang, Houjin Huang, Eiji Osawa, Dean Ho

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

Abstract

Enhanced specificity in drug delivery aims to improve upon systemic elution methods by locally concentrating therapeutic agents and reducing negative side effects. Due to their robust physical properties, biocompatibility and drug loading capabilities, nanodiamonds serve as drug delivery platforms that can be applied towards the elution of a broad range of therapeutically-active compounds. In this work, bovine insulin was non-covalently bound to detonated nanodiamonds via physical adsorption in an aqueous solution and demonstrated pH-dependent desorption in alkaline environments of sodium hydroxide. Insulin adsorption to NDs was confirmed by FT-IR spectroscopy and zeta potential measurements, while both adsorption and desorption were visualized with TEM imaging, quantified using protein detection assays and protein function demonstrated by MTT and RT-PCR. NDs combined with insulin at a 4:1 ratio showed 79.8 ± 4.3% adsorption and 31.3 ± 1.6% desorption in pH-neutral and alkaline solutions, respectively. Additionally, a 5-day desorption assay in NaOH (pH 10.5) and neutral solution resulted in 45.8 ± 3.8% and 2.2 ± 1.2% desorption, respectively. MTT viability assays and quantitative RT-PCR (expression of Ins1 and Csf3/G-csf genes) reveal bound insulin remains inactive until alkaline-mediated desorption. For applications in sustained drug delivery and therapy we have developed a therapeutic protein-ND complex with demonstrated tunable release and preserved activity.

Original languageEnglish (US)
Pages (from-to)5720-5728
Number of pages9
JournalBiomaterials
Volume30
Issue number29
DOIs
StatePublished - Oct 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Drug delivery
  • Insulin
  • Nanodiamond
  • Nanomedicine
  • Wound healing

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