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.