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

Abstract

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.

Light‐Assisted 3D‐Printed Hydrogels for Antibacterial Applications

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In Situ Gelation Strategy for Efficient Drug Delivery in a Gastrointestinal System

“…The gel produced by the in situ gelation strategy has stronger adsorption and binding force with the gastrointestinal wall, which is very friendly to patients with dysphagia. 58,59 The process of realizing the stylized transition from liquid to solid in the patient's body can also improve the stability of the gel and greatly enhance its action time. 60 Here, we present an in situ gelation strategy to immobilize the drug-loaded carrier on the gastrointestinal wall, based on the separated linear polymer molecules and cross-linktriggering-active nanocarriers, to overcome the disadvantageous gastrointestinal conditions for efficient drug delivery (Figure 1).…”