Instant hydrogelation encapsulates drugs onto implants intraoperatively against osteoarticular tuberculosis

J Mater Chem B. 2021 Oct 6;9(38):8056-8066. doi: 10.1039/d1tb00997d.

Abstract

Osteoarticular Tuberculosis (TB) is a challenging issue because of its chronicity and recurrence. Many drug delivery systems (DDSs) have been developed for general chemotherapy. Herein, we take advantage of instant hydrogelation to in situ encapsulate drugs onto implants intraoperatively, optimizing the drug release profile against osteoarticular TB. First-line chemodrugs, i.e. rifampicin (RFP) and isoniazid (INH) are firstly loaded on tricalcium phosphate (TCP). Then, the encapsulating hydrogel is fabricated by dipping in chitosan (CS) and β-glycerophosphate (β-GP) solution and heating at 80 °C for 40 min. The hydrogel encapsulation inhibits explosive drug release initially, but maintains long-term drug release (INH, 158 days; RFP, 53 days) in vitro. Therefore, this technique could inhibit bone destruction and inflammation from TB effectively in vivo, better than our previous ex situ prepared DDSs. The encapsulating technology, i.e. instant hydrogelation of drug-loaded implants, shows potential for regulating the type and ratio of drugs, elastic and viscous modulus of the hydrogel according to the state of illness intraoperatively for optimal drug release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / metabolism
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use*
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Calcium Phosphates / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Chitosan / chemistry
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Femur / pathology
  • Glycerophosphates / chemistry
  • Hydrogels / chemistry*
  • Isoniazid / chemistry
  • Isoniazid / metabolism
  • Isoniazid / pharmacology
  • Isoniazid / therapeutic use
  • Mice
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / physiology
  • Porosity
  • Prostheses and Implants
  • Rifampin / chemistry
  • Rifampin / metabolism
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Tuberculosis, Osteoarticular / drug therapy*

Substances

  • Antitubercular Agents
  • Biocompatible Materials
  • Calcium Phosphates
  • Drug Carriers
  • Glycerophosphates
  • Hydrogels
  • Chitosan
  • tricalcium phosphate
  • Isoniazid
  • Rifampin
  • beta-glycerophosphoric acid