A stimuli-responsive insulin delivery system based on reversible phenylboronate modified cyclodextrin with glucose triggered host-guest interaction

Int J Pharm. 2018 Sep 5;548(1):649-658. doi: 10.1016/j.ijpharm.2018.07.020. Epub 2018 Jul 5.

Abstract

Injection of insulin is an effective therapy to treat most patients with the type I diabetes and some with type II diabetes. Additionally, the release of insulin under specific conditions has attracted widespread interest. In this study, a smart drug carrier that can release insulin depending on the changes in blood glucose levels was designed. Combining two popular molecules through facile synthetic processes, a drug carrier of reversible phenylboronate group modified cyclodextrin (β-CD-EPDME) was fabricated. The drug carrier is composed of cyclodextrin, which can encapsulate insulin, and phenylboronate, which is sensitive to the cis-diols in some saccharides. Moreover, β-CD-EPDME can successfully encapsulate insulin and almost completely release insulin in the presence of glucose. The detached phenylboronic acid moiety triggered by glucose can attack the β-CD cavity and form a host-guest complex, which can force out the encapsulated insulin within the cavity. In addition, the insulin released from the β-CD-EPDME@Insulin complex retains its secondary structure, and the drug carrier has been proven to have low cytotoxicity. Thus, this safe and glucose-responsive drug carrier shows the potential for use in the therapy of diabetes.

Keywords: Cyclodextrin; Diabetics mellitus; Glucose-sensitive; Insulin; Phenylboronic acid.

MeSH terms

  • Animals
  • Boronic Acids* / administration & dosage
  • Boronic Acids* / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Cyclodextrins* / administration & dosage
  • Cyclodextrins* / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Glucose / chemistry*
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / chemistry
  • Insulin* / administration & dosage
  • Insulin* / chemistry
  • Mice

Substances

  • Boronic Acids
  • Cyclodextrins
  • Hypoglycemic Agents
  • Insulin
  • Glucose
  • benzeneboronic acid