New Hydrogel Drug-Delivery Method Targets Colon Inflammation
A new technology has the potential to deliver drugs for inflammatory bowel disease directly to the inflamed part of the colon, using hydrogel, according to a preclinical study published August 12 in Science Translational Medicine.
"Drug therapy involves the careful balancing of intended therapeutic effects and unwanted side effects often related to activities in organs not affected by the disease," write Sufeng Zhang, PhD, from the Massachusetts Institute of Technology in Cambridge, and colleagues. "One approach to maximize beneficial effects and reduce the potential for side effects is targeted drug delivery and release."
The negatively charged hydrogel, made from ascorbyl palmitate, is designed to deliver hydrophobic anti-inflammatory drugs to the positively charged areas of inflammation on the colon. The delivery method enables patients to avoid the effects of systemic drug exposure, as the gel targets only the areas with inflammation.
"Although we cannot exclude the possibility that additional factors may play a role in vivo, our in vitro data strongly suggest charge as the main factor mediating adhesion of IT-hydrogel to the inflamed epithelial surface," explain the authors.
Researchers tested the hydrogel's ability to target inflamed areas in mice and found the gel adhered more to the inflamed epithelial surfaces of the colon than it did to the tissue in healthy controls. Then, to test its effectiveness as a drug delivery method, the researchers loaded it with dexamethasone, an anti-inflammatory corticosteroid, and inserted it as an enema into two types of mice, one genetically bred to have ulcerative colitis and the other chemically induced to have ulcerative colitis.
Compared with the mice administered free dexamethasone (without the gel), the mice receiving the hydrogel-loaded dexamethasone experienced greater reduction in inflammation. The mice receiving the drug in the hydrogel had a mean colitis score of 1.4. The free dexamethasone group had a mean colitis score of 3.3 compared with 3.4 in the untreated controls and 4.1 in the mice receiving the gel alone without medication.
The researchers then tested the hydrogel in human tissue samples from patients with ulcerative colitis (ex vivo). In the six human tissue biopsy samples, the "IT-hydrogel microfibers preferentially adhere to inflamed mucosa in patients with active [ulcerative colitis]," the authors write.
"This technology attempts to address an important clinical challenge and warrants further study based on these preliminary results," Nir Modiano, MD, PhD, director of the Inflammatory Bowel Disease Program and assistant professor of medicine at Oregon Health and Science University in Portland, told Medscape Medical News.
"Achieving optimal concentration of medication at inflamed sites can be a challenge; for example, requiring both oral and rectal administration of mesalamine in some patients to achieve adequate concentrations in the distal colon, or requiring doses of corticosteroids that lead to substantial systemic side effects," explained Dr Modiano, who was not associated with this study.
Although current drug delivery methods can target general regions of the bowel, Dr Modiano said, "this delivery mechanism may offer the potential to allow such drug therapy to be administered with more convenient dosing regimens, greater efficacy at sites of disease involvement, and a lower risk of systemic side effects."
Despite the gel's formulation from compounds generally recognized as safe by the US Food and Drug Administration, "risks and adverse effects of this compound used as a drug delivery mechanism will still need to be assessed in future trials," he added. He also noted that the hydrogel's structure may limit what medications it can deliver, such as an incompatibility with lipophilic drugs.
"Compatibility and stability with different routes of administration will need to be established and could impact what areas of the bowel can be targeted with this agent," he said.
The research was funded by Natural Sciences and Engineering Research Council of Canada, the Department of Biotechnology in India, Harvard Institute of Translational Immunology/Helmsley Trust Pilot Grants in Crohn's Disease, the Alexander von Humboldt Foundation, and the National Institutes of Health. One coauthor holds equity in and sits on the board of directors at Bristol-Myers Squibb, and four coauthors all hold a patent related to this hydrogel technology. The other authors and Dr Modiano have disclosed no relevant financial relationships.
http://www.medscape.com/viewarticle/849516
New Hydrogel Drug-Delivery Method Targets Colon Inflammation
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