Simple Strategy to Protect Lactase Activity in Solid Formulation

Perissinato, Aline Gravinez; Ruela, André Luís Morais; Pereira, Gislaine Ribeiro; Garcia, Jerusa Simone; Trevisan, Marcello G.

doi:10.2174/1567201814666170518125802

Cited by 3 publications

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“…We next evaluated the capacity of LIFT hydrogels for oral delivery of enzymes, which is challenging due to the acidic gastric fluid and proteases present within the gastrointestinal tract 32 . β-galactosidase (lactase) was selected as a model enzyme therapeutic due to the need for prolonged exogenous lactase activity in the stomach to mitigate the symptoms of lactose intolerance [33][34][35][36] . Indeed, lactase activity was found to be rapidly lost when incubated in SGF compared to PBS (Fig.…”

Section: Resultsmentioning

confidence: 99%

Drinkable, liquidin situ-forming and tough hydrogels for gastrointestinal therapeutics

Liu

Pickett

Kuosmanen

et al. 2022

Preprint

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Tablets and capsules are a cornerstone of medicine, but these solid dosage forms can be challenging to swallow for geriatric and pediatric patients. While liquid formulations are easier to ingest, these formulations lack the capacity to localize therapeutics and excipients nor act as controlled release devices. To bridge the advantages of solid and liquid dosage forms, here we describe drug formulations based on liquid in situ-forming and tough (LIFT) hydrogels. Drug-loaded LIFT hydrogels are formed directly in the stomach through the sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by the ingestion of a drug-containing polymer solution of alginate and 4-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels are mechanically tough and able to robustly form in the presence of complex gastric fluid and in vivo in rat and porcine stomachs. LIFT hydrogels are retained within the porcine stomach for up to 24 h, biocompatible, and safely cleared. These hydrogels deliver a total dose comparable to unencapsulated drug but with delayed and lower maximum drug plasma concentrations, providing a method for controlled release that may mitigate drug toxicity. Co-encapsulation of lactase as a model biologic drug and calcium carbonate mitigated gastric-mediated deactivation of encapsulated enzyme in rat and porcine models. We also demonstrate the potential of these hydrogels to encapsulate and protect a model therapeutic bacterium, E. coli Nissle 1917, against acid. LIFT hydrogels present a biocompatible means of tough, double-network hydrogel formation in situ in the gastric cavity, and may expand medication access for patients with difficulty swallowing.

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