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Enhancement Effect of Trypsin on Permeation of Clindamycin Phosphate Through Third-degree Burn Eschar
Azadeh Ghaffari1, Ali Manafi, Hamid Reza Moghimi
1Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Antimicrobial therapy remains to be the most important method of wound infection treatment. Systemically administered antimicrobials may not achieve therapeutic level in wound. On the other hand, in the absence of surgical debridement (due to any reason), most topically applied antimicrobials cannot penetrate the wound in therapeutic amount due to the presence of eschar. Burn eschar is a proteinous structure with some lipid components in which proteins seems to play an important role in the barrier effects of eschar. Therefore, in this study the effect of protein-acting enhancer (trypsin) on permeation of hydrophilic model drug (clindamycin phosphate) was investigated. To perform this investigation, permeation of saturated clindamycin phosphate was studied at 32°C through trypsin-treated and untreated eschar samples for 12 h using home-made static diffusion cells. Third-degree burn eschar samples were separated at the time of surgical debridement (7-14 days post burn) from burned patients. Before each experiment, eschar was hydrated for 12 h and samples were then treated with trypsin solution (1%, w/v) for 4 and 24 h. Clindamycin was measured by a HPLC method developed here. Results showed that after trypsin-treatment for 4 and 24 h, clindamycin phosphate permeation flux was increased significantly by about 1.5 and 2 times and permeation lag-time was decreased by about 2 and 1.3 times respectively. The present results show that permeation of drugs through burn eschar can be increased considerably by trypsin.
Insights
Trypsin treatment significantly enhances clindamycin phosphate penetration through burn eschar, a key barrier in wound healing. This protein-acting enhancer improves drug delivery for effective antimicrobial therapy in burn wound infections.
Area of Science:
- Biomedical Engineering
- Wound Healing Research
- Drug Delivery Systems
Background:
- Antimicrobial therapy is crucial for wound infection treatment, but systemic drugs may not reach therapeutic levels.
- Topical antimicrobials struggle to penetrate burn eschar, a proteinaceous barrier, hindering effective treatment.
- Understanding eschar's barrier properties is vital for improving topical drug delivery in burn wounds.
Purpose of the Study:
- To investigate the effect of trypsin, a protein-degrading enzyme, on the permeation of clindamycin phosphate through burn eschar.
- To evaluate trypsin as a potential enhancer for topical drug delivery across burn eschar barriers.
- To determine the impact of trypsin treatment duration on drug permeation and lag-time.
Main Methods:
- Utilized third-degree burn eschar samples obtained during surgical debridement.
- Hydrated eschar samples for 12 hours, followed by treatment with 1% trypsin solution for 4 and 24 hours.
- Assessed clindamycin phosphate permeation using static diffusion cells at 32°C and analyzed drug concentration via HPLC.
Main Results:
- Trypsin treatment significantly increased clindamycin phosphate permeation flux by approximately 1.5 to 2 times.
- Permeation lag-time was reduced by about 2 times after 4 hours and 1.3 times after 24 hours of trypsin treatment.
- Demonstrated a considerable enhancement in drug permeation through burn eschar following trypsin application.
Conclusions:
- Trypsin effectively enhances the permeation of hydrophilic drugs like clindamycin phosphate through burn eschar.
- Protein degradation by trypsin can overcome the barrier effect of eschar, improving topical drug delivery.
- This approach holds promise for optimizing antimicrobial therapy in burn wound management.
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