From Farm to Pharmacy: Strawberry-Enabled Oral Delivery of Protein Drugs

Abstract

Although oral drug delivery is preferred by patients, it is not possible for proteins because the gastrointestinal tract is not sufficiently permeable. To enable the non-toxic oral uptake of protein drugs, we investigated plant-based foods as intestinal permeation enhancers, hypothesizing that compounds found in food would be well-tolerated by the gastrointestinal tract. Following a screen of over 100 fruits, vegetables, herbs, and fungi, we identified strawberry as a potent enhancer of macromolecular permeability in vitro and in mice. Natural product chemistry techniques identified pelargonidin, an anthocyanidin, as the active compound. In mice, insulin was orally administered with pelargonidin to induce sustained pharmacodynamic effects with doses as low as 1 U/kg and bioactivity of over 100% relative to the current gold standard of subcutaneous injection.Pelargonidin-induced permeability was reversible within two hours of treatment, and one month of daily dosing did not adversely affect mice as determined by weight tracking,

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“…To account for all, insulin is loaded with hydrophobic carriers such as distearyl-dimethylammonium bromide or soybean phospholipid. In addition, different strategies, for example, intestinal coatings 18 , protein inhibitors 19 and penetration enhancers [20][21][22][23][24] , and cell penetrating poly peptides 25 have been utilized. Nowadays, natural and synthetic biodegradable hydrogels are preferred.…”

The Centenary of the Discovery of Insulin: An Update on the Quest for Oral Delivery

“…Perhaps this is a disservice to current efforts, as several recent studies in rodents suggest that substantial oral bioavailability for oral insulin (based indirectly on Area Above the Curve (AAC) calculations from plasma glucose reductions) can be achieved with high-performing new enhancer-and nanoparticle-based systems. Examples of enhancers include ionic liquids (Banerjee et al, 2018) and an strawberry-derived anthocyanidin, pelargonidin (Lamson et al, 2020a), while nanoparticles include anionic silica nanoparticles (Lamson et al, 2020b), and amphiphilic micelle nanocomplexes (Han et al, 2020). These examples for oral insulin delivery, albeit in rodents to date, appear to have surpassed previous efforts in terms of generating doubledigit oral bioavailability.…”

Molecular Pharming to Support Human Life on the Moon, Mars, and Beyond

“…Production of pharmaceuticals in inedible biomass is one way to create physical separation of the food and pharmaceutical streams while maintaining resource flexibility. However, there are situations in which it may be advantageous for merged food and pharmaceutical streams; there are reports in literature on oral delivery of pharmaceuticals in both lettuce and potato [59][60][61] . While promising, this technology is still in nascent stages of development.…”