Sustained and Prolonged Delivery of Protein Therapeutics from Two-Dimensional Nanosilicates

ACS Appl Mater Interfaces. 2019 Feb 20;11(7):6741-6750. doi: 10.1021/acsami.8b17733. Epub 2019 Jan 24.

Abstract

We present a nanoengineered system for sustained and prolonged delivery of protein therapeutics, which has the potential to impact current orthopedic regeneration strategies. Specifically, we introduce two-dimensional nanosilicates with a high surface area and charged characteristics for delivery of active proteins for more than 30 days. The nanosilicates show high binding efficacy without altering the protein conformation and bioactivity. The released proteins are able to maintain high activity as demonstrated by enhanced differentiation of human mesenchymal stem cells at 10-fold lower concentration compared to the exogenous control. Utilizing the nanosilicates as a delivery vehicle could minimize the negative side effects observed because of the use of supraphysiological dosages of protein therapeutics for orthopedic regeneration strategies.

Keywords: bone morphogenetic protein; human mesenchymal stem cells (hMSCs); therapeutic delivery; tissue engineering; transforming growth factor β; two-dimensional (2D) nanomaterials.

MeSH terms

  • Bone Morphogenetic Protein 2* / chemistry
  • Bone Morphogenetic Protein 2* / pharmacokinetics
  • Bone Morphogenetic Protein 2* / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Line
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*

Substances

  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations