Characterisation and Evaluation of Trimesic Acid Derivatives as Disulphide Cross-Linked Polymers for Potential Colon Targeted Drug Delivery

Abstract

Discovery and use of biocompatible polymers offers great promise in the pharmaceutical field, particularly in drug delivery systems. Disulphide bonds, which commonly occur in peptides and proteins and have been used as drug-glutathione conjugates, are reductively cleaved in the colon. The intrinsic stability of a disulphide relative to thiol groups is determined by the redox potential of the environment. The objective of this study was to synthesise a trimesic acid-based disulphide cross-linked polymer that could potentially be used for targeted delivery to the colon. The monomer was synthesised by an amide coupling reaction between trimesic acid and (triphenylmethyl) thioethylamine using a two-step synthesis method. The s-trityl group was removed using a cocktail of trifluoroacetic acid and triethylsilane to expose the thiols in preparation for further polymerisation. The resulting polymers (P10, P15, P21, P25, and P51, generated using different molar ratios) were reduced after 1.5 h of reduction time. Scanning electron microscopy images of the polymers showed spherical, loose, or tight patterns depending on the molar ratio of polymerisation. These polymers also exhibited efficient dissolution under various gastrointestinal conditions. Of the five polymers tested, P10 and P15 appeared to be promising drug delivery vehicles for poorly soluble drugs, due to the hydrophobic nature of the polymers.

Biocompatible disulphide cross-linked sodium alginate derivative nanoparticles for oral colon-targeted drug delivery

“…According to the obtained spectrum, the S-S peak for each nanosphere samples (P1-P5) was identified at 500, 499, 503, 506 and 492 cm À1 , respectively, with the range of 490-510 cm À1 . However, the S-H peak (2550-2600 cm À1 ) was not observed in the samples [9,18,23]. This result confirmed the formation of disulphide cross-linked in nanospheres.…”

“…The unloaded nanosphere morphology was analysed using TEM and FeSEM analyses [6]. To identify S-S and S-H peaks, all the samples were prepared on glass slides and analysed with Raman spectrometer in the spectrum range of 100-4000 cm À1 [9,23].…”

“…The presence of different pH values along the gastrointestinal tract (GI tract) is a considerable challenge for drugs to reach the target sites accurately [5,6]. Many strategies related to colon-specific drug delivery were introduced; these strategies include the covalent linkage between drugs and polymers (prodrug), pH, time and microbial responsive strategies osmotic pressure-controlled drug delivery system [7][8][9] and the use of multiparticulate systems, such as microspheres and nanospheres [10].…”

Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery

“…Environmental and physiological factors in the upper GIT, such as extremely gastric pH and high intestinal enzyme activity in the stomach and small intestine, can degrade drugs [27,28]. Disulfide polymers, which survive the hostile environment of the upper GIT and are only degraded in the reductive environment of the colon, have been utilised as reduction-responsive carriers [16,29,30]. Because sodium alginate is not susceptible to enzymatic and hydrolytic degradation in the GIT, it is an ideal material for preparing nanocarriers that target the colon [28,31].…”

Bridged bicyclic peptides: Structure and function

“…Bicyclic peptides containing side‐chain amide linkages are not limited to straightforward couplings of side‐chain amine and acid functional groups, such as between Lys and Asp residues. Linear peptides possessing three amines (two residues with side chain amines and the N‐terminal amine) have been coupled to the tris‐carboxylic acid, trimesic acid, to generate bicyclic peptides . This cyclization strategy was employed in the discovery of anticachexin C1 ( 13 , Figure ).…”