Tailor-made shape memory stents for therapeutic enzymes: A novel approach to enhance enzyme performance

Int J Biol Macromol. 2021 Aug 31:185:966-982. doi: 10.1016/j.ijbiomac.2021.07.003. Epub 2021 Jul 6.

Abstract

Herein, our suggestion is to immobilize enzymes in-situ on absorbable shape-memory stents instead of injecting therapeutic enzymes into the blood. Chitosan (CHI)-based stents were tailored as novel support and the enzyme-immobilizing ability was elucidated using L-asparaginase (L-ASNase). For developing shape-memory stents, CHI-glycerol (GLY) solution was prepared and further blended with different ratios of polyethylene glycol (PEG), and polyvinyl alcohol (PVA). Afterward, the blends were modified by ionic crosslinking with sodium tripolyphosphate to obtain a shape-memory character. L-ASNase was included in the blends by using in-situ method before ionic crosslinking. The prepared stents, with or without L-ASNase, were comprehensively characterized by using several techniques. Collectively, immobilized L-ASNase exhibited much better performance in immobilization parameters than free one, thanks to its improved stability and reusability. For instance, CHI/GLY/PEG-3@L-ASNase retained about 70% of the initial activity after storage at 30 °C for 2 weeks, whereas the free form lost half of its initial activity. Besides, it retained 73.4% residual activity after 15 consecutive cycles. Most importantly, stent formulations exhibited ~60% activity in the bioreactor system after 4 weeks of incubation. Given the above results, shape-memory stents can be a promising candidate as a new platform for immobilization, especially in the blood circulation system.

Keywords: Biocatalysts; Enhanced stability; Enzyme immobilization; L-asparaginase; Shape-memory stents.

MeSH terms

  • Asparaginase / chemistry
  • Asparaginase / pharmacology*
  • Chitosan / chemistry*
  • Drug Stability
  • Enzyme Stability
  • Enzymes, Immobilized / chemistry
  • Enzymes, Immobilized / pharmacology
  • Hydrogen-Ion Concentration
  • Kinetics
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / pharmacology
  • Polyvinyl Alcohol / chemistry*
  • Stents
  • Temperature
  • Wettability

Substances

  • Enzymes, Immobilized
  • Polyethylene Glycols
  • pegaspargase
  • Polyvinyl Alcohol
  • Chitosan
  • Asparaginase