Targeted Delivery of Miconazole Employing LL37 Fragment Mutant Peptide CKR12-Poly (Lactic-Co-Glycolic) Acid Polymeric Micelles.
Mori. Takeshi T; Yoshida. Miyako M; Hazekawa. Mai M; Ishibashi. Daisuke D; Hatanaka. Yoshiro Y; Kakehashi. Rie R; Nakagawa. Makoto M; Nagao. Toshihiro T; Yoshii. Miki M; Kojima. Honami H; Uno. Rio R; Uchida. Takahiro T
Key Findings
- CKR12‑PLGA micelles loaded with miconazole showed stronger antifungal activity than either component alone.
- The micelles remained stable when diluted and released the drug over time.
- Electron microscopy showed that the micelles damage both the cell wall and membrane of C. albicans.
Practical Outcomes
- For most biohackers, this study offers limited direct use because it focuses on a specialized drug delivery system for hospital‑related fungal infections, not a DIY supplement or protocol. The main takeaway is that combining antimicrobial peptide fragments with existing drugs can boost their effectiveness, a concept that might inspire future self‑experimentation but isn’t ready for everyday application.
Summary
Scientists made tiny particles that combine a piece of the human antimicrobial peptide LL‑37 (called CKR12) with a drug called miconazole. These particles kill the fungus Candida albicans better than the drug alone or the peptide alone, by breaking both the fungus's cell wall and membrane.
Abstract
We previously reported that conjugates of antimicrobial peptide fragment analogues and poly (lactic-co-glycolic) acid (PLGA) enhance antimicrobial activity and that the conjugated micelle structure is an effective tool for antimicrobial drug delivery. In recent years, the delivery of antimicrobial peptides to targets for antimicrobial activity has attracted attention. In this study, we targeted <i>Candida albicans</i>, a causative organism of catheter-related bloodstream infections, which is refractory to antimicrobial agents and is currently a problem in medical practice. We evaluated the antifungal activity of CKR12 (a mutant fragment of the human cathelicidin peptide, LL-37)-PLGA-miconazole (MCZ) micelles using nanotechnology with MCZ delivery. The prepared CKR12-PLGA-MCZ micelles were characterised by measuring dynamic light scattering, zeta potential, dilution stability, and drug release. CKR12-PLGA-MCZ micelles showed higher antifungal activity than CKR12-PLGA micelles and MCZ solution. Furthermore, scanning and transmission electron microscopy suggested that CKR12-PLGA-MCZ micelles disrupted both cell wall and cell membrane of <i>C. albicans</i>. Our results revealed a synergistic effect of antifungal activity using a combination of antimicrobial peptide fragment analogues and MCZ, and that MCZ is a promising tool for the delivery to target microorganisms.
Study Information
pubmed
2021
2021-11-08T00:00:00.000Z
10.3390/ijms222112056
4
39