Hexapeptide decorated β-cyclodextrin delivery system for targeted therapy of bone infection

J Control Release. 2023 Jan:353:337-349. doi: 10.1016/j.jconrel.2022.11.047. Epub 2022 Dec 6.

Abstract

Successfully treating bone infections is a major orthopedic challenge. Clinically, oral, intravenous, or intramuscular injections of drugs are usually used for direct or complementary treatment. However, once the drug enters the system, it circulates throughout the body, leading to an insufficient local dose and limiting the therapeutic effect because of the lack of targeting in the drug system. In this study, β-cyclodextrin, modified with poly (ethylene glycol) [PEG] and aspartic acid hexapeptide (Asp6-β-CD), was used to specifically target the hydroxyapatite (HA) component of the bone. It was then loaded with norfloxacin (NFX) to treat bone infections. The antibacterial ability of NFX was enhanced by loading it into Asp6-β-CD, because the solubility of Asp6-β-CD@NFX increased significantly. Moreover, Asp6-β-CD could target bone tissue in nude mice and showed significantly enhanced accumulation (10 times) than the unmodified β-CD. In addition, in a rat model of osteomyelitis, Asp6-β-CD@NFX targeted HA well and exerted its antibacterial activity, which reduced inflammation and promoted bone tissue repair. This study indicates that the Asp6-β-CD based drug delivery system can efficiently target bone tissue to enable potential applications for treating bone-related diseases.

Keywords: Antibacterial; Aspartic acid hexapeptide; Bone infection; Bone targeted; β-Cyclodextrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Drug Delivery Systems
  • Durapatite
  • Mice
  • Mice, Nude
  • Osteomyelitis* / drug therapy
  • Pharmaceutical Preparations
  • Polyethylene Glycols
  • Rats
  • beta-Cyclodextrins*

Substances

  • Anti-Bacterial Agents
  • beta-Cyclodextrins
  • Polyethylene Glycols
  • Pharmaceutical Preparations
  • Durapatite