Polymeric Films for the Encapsulation, Storage, and Tunable Release of Therapeutic Microbes

Microbe-based therapeutics (MBTs) are an emerging therapeutic modality for treating gastrointestinal infections and inflammatory bowel diseases. Current formulations for oral delivery of MBTs use capsules to achieve safe gastric transit, but oral formulations that control the spatiotemporal concentration of MBTs are yet to be developed, despite well-established connections between all therapeutics and their location, concentration, and distribution at sites of action. The development of a multi-functional polymer-based encapsulation system to formulate MBTs for enhanced storage and delivery through formulation of a model MBT, Lactobacillus casei ATCC393, is reported here. This approach enables the additive inclusion of excipients and polymers to grant specific functions, toward the development of a modular MBT platform. Through addition of established excipients, the formulation provides long-term storage of the encapsulated MBT. By adding higher molecular weight polymers, the release kinetics of the encapsulated MBTs can be modified. The inclusion of a mucoadhesive polymer significantly increases the adhesion force between the formulation and the intestinal tissue. Together, mucoadhesive and sustained release properties can be used to modulate the spatiotemporal concentration of MBTs. The formulation is compatible with standard oral capsules, thus maintaining existing clinical advantages of oral capsules while providing new functions from film encapsulation

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Background: Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods: A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results: A total of 4164 patients were included, with a median age of 68 (i.q.r. 57\u201375) years (54\ub79 per cent men). Some 1153 (27\ub77 per cent) received NSAIDs on postoperative days 1\u20133, of whom 1061 (92\ub70 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4\ub76 versus 4\ub78 days; hazard ratio 1\ub704, 95 per cent c.i. 0\ub796 to 1\ub712; P = 0\ub7360). There were no significant differences in anastomotic leak rate (5\ub74 versus 4\ub76 per cent; P = 0\ub7349) or acute kidney injury (14\ub73 versus 13\ub78 per cent; P = 0\ub7666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35\ub73 versus 56\ub77 per cent; P < 0\ub7001). Conclusion: NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement