Easy Access to Supramolecular Gels of the Nonsteroidal Anti‐inflammatory Drug Diflunisal: Synthesis, Characterization, and Plausible Biomedical Applications

Abstract

By exploiting salt formation, a new series of primary ammonium monocarboxylate salts of a nonsteroidal anti-inflammatory drug, namely, diflunisal, was synthesized. The majority of the salts thus synthesized turned out to be good gelators of various solvents, including the solvents (e.g., methyl salicylate and pure water) typically used for topical gel formulation. Single-crystal X-ray diffraction studies of a few gelator and nongelator salts in the series revealed details of the hydrogen-bonding networks present in the salts. Furthermore, one such gelator salt, namely, the diflunisal salt of serinol, was found to be biocompatible (MTT assay), and its anti-inflammatory (PGE2 assay) response turned out to be as good as that of the parent drug, which is indicative of its potential in biomedical applications.

Design and synthesis of nanofibers of self-assembled de novo glycoconjugates towards mucosal lining restoration and anti-inflammatory drug delivery

“…The designed molecular platform can easily incorporate various anti-inflammatory drugs, as demonstrated in our recent works. 12a Moreover, we have incorporated olsalazine into a biocompatible peptide motif 12c that allows mesalazine to be released from the hydrogel upon reduction by the azoreductase secreted by colonic microflora. 15a Moreover, we aim to engineer the hydrogels to pass through the stomach, to reach the target organ, colon, and to adhere onto the disrupted mucosal surfaces.…”

“…As the first step towards to that challenging goal, we explore the structural requirements of the molecules that self-assemble in water and bear glycogens and NSAIDs. Based on the previous studies of hydrogelators containing glycogens 11 and NSAID, 12 we covalently link peptides (e.g., nap-phe-phe 13 ), saccharides (e.g., glucosamine 14 ) and an anti-inflammatory drug (i.e., olsalazine 15 ) to generate a new glycoconjugate. We show that the obtained molecules, as multifunctional glycoconjugates, self-assemble to form hydrogels composed of 3D networks of nanofibers under an acidic conditions.…”

Supramolecular Synthon Approach in Designing Molecular Gels for Advanced Therapeutics

“…Following similar strategy, Dastidar et al. further developed topical gels from a series of PAM salts of a well‐known NSAID namely diflunisal . In order to study the robustness of PAM synthon and its implication on gelation, some of the primary amines used in this work contained additional hydrogen bonding functionality; majority of the salts ( G64 – G67 ) turned out to be gelators of various solvents including methyl salicylate and pure water.…”

Rationally Developed Organic Salts of Tolfenamic Acid and Its β‐Alanine Derivatives for Dual Purposes as an Anti‐Inflammatory Topical Gel and Anticancer Agent

“…[56] Among these, the primary ammonium monocarboxylate (PAM) synthoni sp articularly important (Scheme 1). [72][73][74] The anti-inflammatory activity of an onsteroidal anti-inflammatoryd rug (NSAID) is known to follow the cyclooxygenase( COX) pathway by acting as an inhibitor of COX enzymes, thereby reducing the intracellularc oncentration of prostaglandin E 2 (PGE 2 ), the consequenceo fw hich is ar eduction of inflammation of cells. [58,59] Recently, we launched an initiativet od evelop drug-delivery systems that would act in as elf-delivery manner.…”

“…[62][63][64][65][66][67][68][69][70][71] We, on the other hand, demonstrated that the supramolecular synthon approach, following the organic salt route, was useful in developing self-delivery systems. [72][73][74] The anti-inflammatory activity of an onsteroidal anti-inflammatoryd rug (NSAID) is known to follow the cyclooxygenase( COX) pathway by acting as an inhibitor of COX enzymes, thereby reducing the intracellularc oncentration of prostaglandin E 2 (PGE 2 ), the consequenceo fw hich is ar eduction of inflammation of cells. [75] However,o rally administrated NSAIDs have severals idee ffects, such as gastrointestinal bleeding [76] and worsening of asthma, [77] whichc an be easily avoided if the drug molecule can be converted into at opical gel that is then conveniently applied to treat inflammationinaself-delivery fashion.…”