Selective Delivery of Clindamycin Using a Combination of Bacterially Sensitive Microparticle and Separable Effervescent Microarray Patch on Bacteria Causing Diabetic Foot Infection

Pharm Res. 2024 May;41(5):967-982. doi: 10.1007/s11095-024-03697-z. Epub 2024 Apr 18.

Abstract

Introduction: Diabetic foot infection (DFI) is one of the complications of diabetes mellitus. Clindamycin (CLY) is one of the antibiotics recommended to treat DFI, but CLY given orally and intravenously still causes many side effects.

Methods: In this study, we encapsulated CLY in a bacteria sensitive microparticle system (MP-CLY) using polycaprolactone (PCL) polymer. MP-CLY was then delivered in a separable effervescent microarray patch (MP-CLY-SEMAP), which has the ability to separate between the needle layer and separable layer due to the formation of air bubbles when interacting with interstitial fluid in the skin.

Result: The characterization results of MP-CLY proved that CLY was encapsulated in large amounts as the amount of PCL polymer used increased, and there was no change in the chemical structure of CLY. In vitro release test results showed increased CLY release in media cultured with Staphylococcus aureus bacteria and showed controlled release. The characterization results of MPCLY-SEMAP showed that the developed formula has optimal mechanical and penetration capabilities and can separate in 56 ± 5.099 s. An ex vivo dermatokinetic test on a bacterially infected skin model showed an improvement of CLY dermatokinetic profile from MP-CLY SEMAP and a decrease in bacterial viability by 99.99%.

Conclusion: This research offers proof of concept demonstrating the improved dermatokinetic profile of CLY encapsulated in a bacteria sensitive MP form and delivered via MP-CLY-SEMAP. The results of this research can be developed for future research by testing MP-CLY-SEMAP in vivo in appropriate animal models.

Keywords: bacterially sensitive microparticle; clindamycin; dermatokinetic; diabetic foot infection; polycaprolactone; separable effervescent microarray patch.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / pharmacology
  • Clindamycin* / administration & dosage
  • Diabetic Foot* / drug therapy
  • Diabetic Foot* / microbiology
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Humans
  • Polyesters / chemistry
  • Skin* / metabolism
  • Skin* / microbiology
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus* / drug effects
  • Transdermal Patch

Substances

  • Clindamycin
  • Anti-Bacterial Agents
  • polycaprolactone
  • Polyesters
  • Drug Carriers