Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Abstract

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

A Proresolving Peptide Nanotherapy for Site‐Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota

“…[13,14] A recent study revealed the potential of Ac2-26 for the treatment of colitis after intraperitoneal or intramucosal injection of Ac2-26 in nanoparticles (NPs). [16][17][18][19][20][21] However, there are still tremendous challenges in the design and development of translational nanovehicles for oral delivery of macromolecular therapeutics, [16,[22][23][24][25] although different nanotherapies have been developed for targeted treatment of IBD. On the other hand, patient-friendly oral delivery is highly preferred for treatment of gastrointestinal and chronic diseases, owing to its convenience, high patient compliance, desirable cost-effectiveness, and good safety profile.…”

Ivermectin to reduce malaria transmission II. Considerations regarding clinical development pathway

“…While there have to be enough clusters to meet tests for robustness given hypothesized effect size, and the specifics of the control intervention package may vary, there are, conceptually, some key elements to consider:

A vector control package representative of strategies and epidemiology for that region must be included.

Appropriate surveillance system for identification of cases and appropriate response systems must be in place. This includes reporting systems to ensure timely facility-based reporting.

The impact of ivermectin MDA is modelled to be proportionally higher in areas of high transmission [44, 56], giving a theoretical power advantage to that context, although trials under different scenarios (higher endemicity to accelerate the path to elimination and at low levels of endemicity to accelerate crashing transmission) have been considered and would be valuable in different context. …”

Advances in Materials and Structures for Ingestible Electromechanical Medical Devices

“…Forexample,the abrupt and conserved change in pH from the stomach to the duodenum is the basis for creating pHresponsive polymers such as the commercially successful class polymers termed Eudrogit ,atrade name for copolymers based on methacrylic acid and ethyl methacrylate.Eudrogit polymers are most commonly utilized as aenteric coatings to protect sensitive payloads from the caustic environment of the stomach. [49] High molecular weight poly(acryloyl 6-aminocaproic acid; M w % 400 kDa; > 3) can be combined with linear poly-(methacrylic acid-co-ethyl acrylate) to create hydrated elastomers ( Figure 6).…”