Researchers successfully delivered the immunosuppressant tacrolimus in a self-assembled hydrogel, enabling localized therapy in patients receiving a tissue graft transplant of the leg, hand or face.
Vascularized composite allotransplantation is the current paradigm to ensure graft survival, but involves chronic immunosuppression and systemic rather than localized delivery, subjecting the patient to side effects. In contrast the experimental hydrogel stays inert until it senses an inflammation or immune response from the transplant site, which causes it to release the drug there, where it is needed.
Immunosuppressive drugs are rapidly absorbed into the bloodstream and reach a peak concentration before being cleared, the team previously explained in the Sri Lankan paper The Nation. This limits the possibilities of the drug by shortening the window of acceptability, but by loading the drugs into hydrogels, higher concentrations can last much longer without causing an initial overload.
"This new approach to delivering immunosuppressant therapy suggests that local delivery of the drug to the grafted tissue has benefits in reducing toxicity, as well as markedly improving therapeutic outcomes, and may lead to a paradigm shift in clinical immunosuppressive therapy in transplant surgery," said Jeff Karp of the Division of Biomedical Engineering at Brigham and Women's Hospital in Boston in a statement.
According to the study's abstract in the Aug. 13 edition of Science Translational Medicine, median graft survival was more than 100 days in rats treated with the tacrolimus delivered via hydrogel, compared to 33.5 days in rats treated with tacrolimus only and 11 days in rats that were either untreated or treated with hydrogel only.
"Continuous release of the drugs irrespective of disease severity is a hallmark of existing drug delivery vehicles and could be a thing of the past. Inflammation-directed drug release offers 'judicious use of locally injected drug' that extends the release for months while eliminating systemic toxicity," said study co-author Robert Rieben, a professor of transplantation immunology at the University of Bern in Switzerland, in the statement.
And co-author Praveen Kumar Vemula of the Institute for Stem Cell Biology and Regenerative Medicine in Bangalore, India, said that the technique could have implications for other diseases as well: "This approach should also improve patient compliance, as it obviates the need for daily medications. Also, we plan to expand this prototype for the treatment of numerous diseases such as psoriasis, arthritis and cancer."
Hydrogel is a hydrophilic, jello-like substance that has many uses in drug delivery. In June, Harvard University researchers announced that they have developed a system for releasing high doses of drugs in short bursts using ultrasound and self-healing hydrogel.
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