Localised Delivery of Macromolecules to the Large Intestine: Translation to Clinical Trials

Colonic drug delivery: Formulating the next generation of colon-targeted therapeutics

“…Whilst a significant proportion of patients with IBD will require parenteral treatment at some point in their lives, colontargeting formulation strategies could facilitate oral/rectal administration of current parenteral-only drugs, such as biologics [160]. Several clinical studies have demonstrated how modified release coatings can enable the delivery of antibodies for the treatment of IBD, these have recently been reviewed by Brayden [33]. Where systemic delivery of biologics is desired, formulations may need to incorporate permeation enhancers, such as medium chain fatty acids or salcaprozate sodium, to enable passage across the colonic epithelium [161,162].…”

“…Where systemic delivery of biologics is desired, formulations may need to incorporate permeation enhancers, such as medium chain fatty acids or salcaprozate sodium, to enable passage across the colonic epithelium [161,162]. At present there are 5 FDA-approved products that deliver peptides orally for systemic action, these include Rybelsus® (semaglutide) and Mycapssa® (octreotide) [33]. As the formulation strategy will be unique to each colonic drug delivery project, it is important to appreciate the myriad of options when designing a multi-stimuli system.…”

“…The prodrug strategy is still utilised for colonic delivery, for example an azo prodrug of tofacitinib was recently shown to effectively treat a mouse model of IBD [32]. Similarly, gut restriction of molecules (particularly peptides) could enable local colonic action by preventing systemic absorption [33]. However, design of prodrugs/gut-restricted therapeutics is drug-specific and can require lengthy regulatory approval [34].…”

Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation

“…Oral delivery of proteins and peptides has been gaining predominance since the 1970s, when it was observed in the clinic that intact macromolecules can be absorbed from the gastrointestinal (GI) tract. Despite the challenges posed by the barrier mechanisms within the GI tract, oral delivery of macromolecules can provide many benefits to patients over injections [1]. Efforts have continued over the years in both academia and industry to achieve absorption of large molecules in therapeutically meaningful doses orally that could potentially change the standard of care.…”