Facile synthesis and self-assembly of pharmaceutically important oligobenzylidene-d-sorbitol dialdehydes: direct encapsulation and stimuli responsive delivery of H2S†
Abstract
Over the past two decades, the development of stimuli-responsive drug delivery materials for healthcare applications has drawn significant attention. A detailed investigation of one of the critical endogenously produced gaseous molecules, H2S, revealed its significance in promoting tissue regeneration, angiogenesis, organelle function, stress and antioxidant effect. Even though a continuous delivery of H2S can suppress cancer cell progression, its administration as a therapeutic drug has become highly challenging because of its gaseous nature and reactivity. By considering the limitations of the existing H2S delivery, we have developed a smart, biocompatible drug delivery system for the direct delivery of H2S from bio-based resources. In this report, we have synthesized oligo[1,3:2,4-(O-benzylidene)-D-sorbitol]-dialdehyde (OBSDA) using an FDA-approved GRAS chemical and environmentally benign protocol in good yields. The ability of OBSDA to self-assemble into supramolecular gels was systematically studied in a broad range of solvents. To our fortune, OBSDA displayed gelation in N-methyl pyrrolidone (NMP), one of the FDA-approved solvents displaying a well-established safety profile and anti-inflammatory properties. Molecular level interactions responsible for the formation of the supramolecular gels have been identified using NMR and FTIR analysis. The self-assembly, mechanism, morphology and strength of the gel were systematically studied using XRD, scanning electron microscopy and rheological studies. For the first time, we report the direct in situ encapsulation of H2S into the gel formed by using a pharmaceutical solvent, NMP, by gaining input from the Purisol process. A stimuli-responsive delivery of encapsulated H2S via gel-to-sol transition has been achieved by the addition of acidic buffer. The reported precise delivery will enable future studies of the physiological role of H2S in various biological processes.