Synthesis and Coordination Properties of a Water-Soluble Material by Cross-Linking Low Molecular Weight Polyethyleneimine with Armed Cyclotriveratrilene.

In this study, a full organic and water-soluble material was synthesized by coupling low molecular weight polyethylenimine (PEI-800) with cyclotriveratrilene (CTV). The water-soluble cross-linked polymer contains hydrophobic holes with a high coordination capability towards different organic drug molecules. The coordinating capability towards hydrophilic drugs (doxorubicin, gatifloxacin and sinomenine) and hydrophobic drugs (camptothecin and celastrol) was analyzed in an aqueous medium by using NMR, UV-Vis and emission spectroscopies. The coordination of drug molecules with the armed CTV unit through hydrophobic interactions was observed. In particular, celastrol exhibited more ionic interactions with the PEI moiety of the hosting system. In the case of doxorubicin, the host-guest detachment was induced by the addition of ammonium chloride, suggesting that the intracellular environment can facilitate the release of the drug molecules.

Functionalization of Polyethyleneimine with Hollow Cyclotriveratrylene and Its Subsequent Supramolecular Interaction with Doxorubicin.

In this paper, a modified Cyclotriveratrylene was synthesized and linked to a branched Polyethylenimine, and this unique polymeric material was subsequently examined as a potential supramolecular carrier for Doxorubicin. Spectroscopic analysis in different solvents had shown that Doxorubicin was coordinated within the hollow-shaped unit of the armed Cyclotriveratrylene, and the nature of the host-guest complex revealed intrinsic Van der Waals interactions and hydrogen bonding between the host and guest. The strongest interaction was detected in water because of the hydrophobic effect shared between the aromatic groups of the Doxorubicin and Cyclotriveratrylene unit. Density functional theory calculations had also confirmed that in the most stable coordination of Doxorubicin with the cross-linked polymer, the aromatic rings of the Doxorubicin were localized toward the Cyclotriveratrylene core, while its aliphatic chains aligned closer with amino groups, thus forming a compact supramolecular assembly that may confer a shielding effect on Doxorubicin. These observations had emphasized the importance of supramolecular considerations when designing a novel drug delivery platform.

Redox-Sensitive Linear and Cross-Linked Cystamine-Based Polymers for Colon-Targeted Drug Delivery: Design, Synthesis, and Characterisation.

Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, N1, N6-bis(2-(tritylthio)ethyl)adipamide (2) was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of 2 was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, N1, N6-bis(2-mercaptoethyl)adipamide (3) to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.

Tuning of the Electro-Optical Properties of Tetraphenylcyclopentadienone via Substitution of Oxygen with Sterically-Hindered Electron Withdrawing Groups.

In this report, the substitution of the oxygen group (=O) of Tetraphenylcyclopentadienone with =CR2 group (R = methyl ester or nitrile) was found to have tuned the electro-optical properties of the molecule. Although both groups are electrons withdrawing in nature, their absorption from UV-vis spectra analysis was observed to have been blue-shifted by methyl ester substitution and red-shifted by nitrile substitution. Interestingly, these substitutions helped to enhance the overall intensity of emission, especially in the context of methyl ester substitution whereby the emission was significantly boosted at higher concentrations due to hypothesized restrictions of intramolecular motions. These observations were explained through detailed descriptions of the electron withdrawing capability and steric properties of the substituents on the basis of density functional theory calculations.

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

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.