Multifunctional hydrogels for the delivery of drugs and nutraceuticals for the treatment of inflammatory bowel disease
Authors: Murtagh A. , Higginbotham C. , Heavey P. 
Published: December 2024

Inflammatory bowel disease (IBD) is chronic relapsing condition that affects 6.8 million people worldwide and unfortunately there is no cure(1). Treatment, typically via anti-inflammatory medications, aims to induce remission and for many they are effective but for some they can lead to unpleasant side effects(2,3). Anti-inflammatory nutraceuticals such as curcumin have, in recent years, shown potential for the treatment of IBD, however, there are limitations for its use including poor solubility and inadequate concentrations at target tissues(4–6).Targeted delivery systems have the potential to reduce drug side effects and overcome some of the challenges for nutraceuticals. Hydrogels are a type of delivery system that can be easily tuned to target specific tissues, but there are challenges incorporating active ingredients such as curcumin. Therefore, microspheres can help overcome some challenges including solubility issues and act as a carrier for drugs and nutraceuticals within the hydrogel. Hence, the aim of the current study was to incorporate curcumin and dexamethasone loaded microspheres into a hydrogel that can target the specific features of IBD.

An emulsion solvent evaporation technique was utilised to entrap dexamethasone (0.4wt%) and curcumin (0.4wt%) in polylactic acid-polyethylene glycol microspheres. Subsequently, 100 mg (0.5wt%) of each (dexamethasone and curcumin microspheres) were incorporated into hydrogels which were synthesised using polyethylene glycol dimethacrylate (PEGDMA), acrylic acid, water and a photoinitiator, via UV photopolymerisation. Encapsulation of dexamethasone and curcumin and their release from microspheres were determined via UV spectroscopy. Characterisation tests including swelling studies in pH buffers 2.2 and 6.8 and ionic charge studies in positively methylene blue in both pH 2.2 and 6,8, were carried out to determine the hydrogels-co-microspheres ability to target specific features of IBD. Statistical analysis (paired T-Test) was carried out using OriginLab.

Encapsulation studies showed that on average 29% of the dexamethasone and 92% of the curcumin were successfully encapsulated into the microspheres, however the subsequent release measured over 4 weeks was low with higher release of dexamethasone (17.45% ± 0.09%) compared to curcumin (0.02% ± 0.0007%). Swelling studies demonstrated the equilibrium water content (EWC), the ability of the hydrogel-co-microsphere to uptake its surrounding solution, with differences observed in response to changes in pH. In pH 6.8 they had a higher EWC compared to pH 2.2 (EWC = 53% ± 0.06% and 43% ± 0.01%, respectively). The ionic charge of the hydrogel-co-microspheres was negative as indicated by uptake of positively charged methylene blue solution, with uptake in pH 6.8 greater than in pH 2.2 (4.7µl ± 0.14 V 3.5µl ± 0.09, respectively p<0.05).

Although further work is required, an advanced delivery system of microspheres encapsulating drugs and nutraceuticals embedded in a hydrogel that can target specific features of IBD has great potential for improving therapeutic efficacy.