Decellularized skeletal muscle as an in vitro model for studying drug-extracellular matrix interactions
| Autor: | Karen L. Christman, Gerry R. Boss, Jean W. Wassenaar |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Materials science
Swine Sus scrofa Biophysics Drug Evaluation Preclinical Bioengineering Pharmacology In Vitro Techniques Ligands Injections Intramuscular Article Biomaterials Extracellular matrix Tissue engineering In vivo Polysaccharides medicine Animals Muscle Skeletal Decellularization Sulfates Skeletal muscle Hydrogels Extracellular Matrix Rats medicine.anatomical_structure Drug development Intramuscular Absorption Mechanics of Materials Drug delivery Ceramics and Composites Cobamides Collagen Drug metabolism |
| Zdroj: | Biomaterials. 64 |
| ISSN: | 1878-5905 |
| Popis: | Several factors can affect drug absorption after intramuscular (IM) injection: drug solubility, drug transport across cell membranes, and drug metabolism at the injection site. We found that potential interactions between the drug and the extracellular matrix (ECM) at the injection site can also affect the rate of absorption post-injection. Using decellularized skeletal muscle, we developed a simple method to model drug absorption after IM injection, and showed that the nature of the drug-ECM interaction could be investigated by adding compounds that alter binding. We validated the model using the vitamin B12 analog cobinamide with different bound ligands. Cobinamide is being developed as an IM injectable treatment for cyanide poisoning, and we found that the in vitro binding data correlated with previously published in vivo drug absorption in animals. Commercially available ECM products, such as collagen and GelTrex, did not recapitulate drug binding behavior. While decellularized ECM has been widely studied in fields such as tissue engineering, this work establishes a novel use of skeletal muscle ECM as a potential in vitro model to study drug-ECM interactions during drug development. |
| Databáze: | OpenAIRE |
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