1. In vivo targeting through click chemistry
- Author
-
Yevgeny Brudno, Michael Aizenberg, David J. Mooney, Brian J. Kwee, Neel Joshi, and Rajiv Desai
- Subjects
Drug ,Azides ,Alginates ,media_common.quotation_subject ,Pharmacology ,Biochemistry ,Cyclooctanes ,Heterocyclic Compounds, 1-Ring ,Mice ,Drug Delivery Systems ,Glucuronic Acid ,In vivo ,Drug Discovery ,Benzene Derivatives ,Medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,media_common ,Fluorescent Dyes ,business.industry ,Hexuronic Acids ,Muscles ,Organic Chemistry ,Hydrogels ,Small molecule ,Combinatorial chemistry ,Targeted drug delivery ,Alkynes ,Drug delivery ,Click chemistry ,Molecular Medicine ,Click Chemistry ,Bioorthogonal chemistry ,business ,Wound healing - Abstract
Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery. Drug-eluting devices implanted during invasive surgery allow the controlled presentation of drugs at the disease site, but cannot be modified once the surgery is complete. We demonstrate that bioorthogonal click chemistry can be used to target circulating small molecules to hydrogels resident intramuscularly in diseased tissues. We also demonstrate that small molecules can be repeatedly targeted to the diseased area over the course of at least one month. Finally, two bioorthogonal reactions were used to segregate two small molecules injected as a mixture to two separate locations in a mouse disease model. These results demonstrate that click chemistry can be used for pharmacological drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.
- Published
- 2014