A dual cross-linked biodegradable polyelectrolyte hydrogel actuator for bi-directional pH-responsive drug release

Abstract

Here, we present a dual cross-linked pH-responsive hydrogel platform for controlled drug release in acidic and basic pathophysiological pH media. The hydrogel was strategically developed using oppositely charged polyelectrolytes, namely gelatin and carboxymethyl cellulose (CMC). This hydrogel was stabilised by adding a cross-linking agent, 1,4-butanediol diglycidyl ether (BDDE). The hydrogel could be formulated in about 2 h, at pH 9, without any specialised instruments. The prepared hydrogel senses both lower and higher environmental pH and swells to deliver the drug to the intended application site. Importantly, the prepared hydrogel was found to exhibit an equal percentage (∼60%) of shrinkage (at pH 7.4) and swelling (at pH 4 and 9). The novelty of the proposed hydrogel lies in its reversible sensitivity to pH for on-demand drug delivery in both acidic environments (e.g. tumour sites) and basic environments (e.g. chronic wounds). Neomycin sulphate, a common drug effective against chronic wounds and cancer, could be entrapped within the hydrogel with excellent entrapment efficiency (∼84%). Entrapped neomycin sulphate is released on demand in acidic (pH ∼6) and basic (pH ∼9) media. This polyelectrolyte-based hydrogel is bio-degraded within 21 days. Changes in the hydrogel's morphology were observed through SEM. The reported hydrogel exhibits remarkable biocompatibility also for HeLa cell lines. Therefore, this prepared hydrogel may be a promising pH-responsive biomaterial for drug delivery applications, which can easily be scaled up in the future.