Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis
| Autor: | Harald Gollnick, Siegfried Ansorge, D. Mahnkopf, Michael Täger, Sven R Quist, Ute Bank, A. Heimburg, G. Koch |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Microdialysis Swine media_common.quotation_subject Drug Compounding Skin Absorption Biological Availability Pilot Projects Dermatology Pharmacology Administration Cutaneous High-performance liquid chromatography Dipeptidyl peptidase 03 medical and health sciences Dermis Interstitial fluid medicine Animals Dipeptidyl-Peptidases and Tripeptidyl-Peptidases media_common Enzyme Assays Chemistry Penetration (firestop) Bioavailability 030104 developmental biology medicine.anatomical_structure Models Animal |
| Zdroj: | Clinical and experimental dermatology. 42(6) |
| ISSN: | 1365-2230 |
| Popis: | SummaryBackground Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body. Aim To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families. Methods Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography. Results Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel. Conclusion It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up. |
| Databáze: | OpenAIRE |
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