Researchers describe a system for topical delivery of drugs to patients with ulcerative colitis (UC). A polymer that holds and then releases UC drugs such as budesonide and mesalamine is liquid at room temperature, but turns into a viscous gel upon reaching body temperature, they report in the July issue of Gastroenterology.
Systemic therapies for inflammatory bowel diseases are associated with an increased risk of infections and malignancies. Topical therapies reduce systemic exposure, but can be difficult for patients to retain or have limited proximal distribution.
Sidhartha R. Sinha et al developed a thermo-sensitive drug delivery system that has the advantages of a liquid enema but does not have retention issues. The system comprises a nonionic surfactant copolymer, consisting of hydrophilic polyethylene glycol and hydrophobic polypropylene glycol blocks that can be used to deliver budesonide and mesalamine (see figure).
At low temperature, the subunits assemble as hydrated micelles. At high temperature, the polymer is dehydrated, dissociating the micelles into a gel. The gelled polymer coats the mucosa, allowing the encapsulated drug to be released.
Sinha et al tested their agent in C57BL/6 mice with dextran sulfate sodium (DSS)-induced colitis. Mice given budesonide-containing gel gained more weight and had reduced histologic and biologic features of colitis than mice given the polymer alone or liquid drugs via enema.
Image analysis showed that enemas delivered with and without the polymer reached similar distances in the colons of mice, but the polymer was retained longer in both healthy and inflammed colon.
The system did not appear to alter bowel function because mice given the budesonide polymer continued to gain weight for 4 additional weeks and have normal bowel movements.
Sinha et al showed that a mesalamine-containing polymer also reduced weight loss, colon shortening, and histologic signs of inflammation mice with DSS-induced colitis. These effects were not model- or strain-specific, because they reduced the severity of trinitrobenzene sulfonic acid-induced colitis in Balb/c mice.
Long-term studies are needed to determine the safety of this system in patients with colonic strictures. However, the authors say that most patients with inflammatory bowel diseases and all patients with ulcerative colitis can benefit from topical therapies—particularly during acute flares, which can often be managed with exclusive use of topical agents.
Because of its greater proximal reach and retention, the drug-containing polymer of Sinha et al could allow for less frequent administration and increased patient compliance.The authors state that this system might be developed to treat other diseases.