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Perni, Stefano; Prokopovich, Polina (2017)
Publisher: Elsevier
Journal: Nanomedicine
Languages: English
Types: Article
Subjects: Materials Science(all), Dexamethasone, RS, Medicine (miscellaneous), Original Article, PBAE, OA, Pharmaceutical Science, Biomedical Engineering, Cartilage, Molecular Medicine, Bioengineering
The efficient delivery of therapeutic molecules to the cartilage of joints is a major obstacle in developing useful therapeutic interventions; hence, a targeted drug delivery system for this tissue is critical. We have overcome the challenge by developing a system that employs electrostatic attraction between the negatively charged constituents of cartilage and a positively charged polymer, poly-beta amino esters (PBAEs). We have demonstrated cartilage uptake of dexamethasone (DEX) covalently bound to the PBAE was doubled and retention in tissues prolonged compared to the equivalent dose of the commercial drug formulation. Moreover, no adverse effects on chondrocytes were found. Our data also show that PBAEs can bind not only healthy cartilage tissues but also enzymatically treated cartilage mimicking early stages of OA. Our PBAEs-prodrug technology's advantages are fourfold; the specificity and efficacy of its targeting mechanism for cartilage, the ease of its production and the low-cost nature of the delivery system.

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