Preparation, Characterization and Evaluation of the Anti-Inflammatory Activity of Epichlorohydrin-ß-Cyclodextrin/Curcumin Binary Systems Embedded in a Pluronic®/Hyaluronate Hydrogel.

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-ß-CD (EpißCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpißCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpißCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpißCD complex is a great alternative to treat topical inflammatory diseases.

Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-ß-Cyclodextrin Polymer, and Antifungal Effect.

It has been reported that the structure of the Schiff bases is fundamental for their function in biomedical applications. Pyridine Schiff bases are characterized by the presence of a pyridine and a phenolic ring, connected by an azomethine group. In this case, the nitrogen present in the pyridine is responsible for antifungal effects, where the phenolic ring may be also participating in this bioactivity. In this study, we synthesized two new pyridine Schiff Bases: (E)-2-[(3-Amino-pyridin-4-ylimino)-methyl]-4,6-difluoro-phenol (F1) and (E)- 2-[(3-Amino-pyridin-4-ylimino)-methyl]-6-fluoro-phenol (F2), which only differ in the fluorine substitutions in the phenolic ring. We fully characterized both F1 and F2 by FTIR, UV-vis, 1H; 13C; 19F-NMR, DEPT, HHCOSY, TOCSY, and cyclic voltammetry, as well as by computational studies (DFT), and NBO analysis. In addition, we assessed the antifungal activity of both F1 (two fluorine substitution at positions 4 and 6 in the phenolic ring) and F2 (one fluorine substitution at position 6 in the phenolic ring) against yeasts. We found that only F1 exerted a clear antifungal activity, showing that, for these kind of Schiff bases, the phenolic ring substitutions can modulate biological properties. In addition, we included F1 and F2 into in epichlorohydrin-ß-cyclodextrin polymer (ßCD), where the Schiff bases remained inside the ßCD as determined by the ki , TGA, DSC, and SBET. We found that the inclusion in ßCD improved the solubility in aqueous media and the antifungal activity of both F1 and F2, revealing antimicrobial effects normally hidden by the presence of common solvents (e.g., DMSO) with some cellular inhibitory activity. The study of structural prerequisites for antimicrobial activity, and the inclusion in polymers to improve solubility, is important for the design of new drugs.

Synthesis, characterization and application of epichlorohydrin-ß-cyclodextrin polymer.

Cyclodextrins, the macrocyclic compounds are renowned for their inclusion ability. Several chemical and polymerized derivatives of parent cyclodextrins are synthesized to improve the physicochemical/biopharmaceutical properties of drug and inclusion capacity of cyclodextrin. This review article recapitulates the potential aspects of polymerized water-soluble derivative of ß-cyclodextrin viz. epichlorohydrin-ß-cyclodextrin polymer in different areas of drug delivery. Polymerized cyclodextrin combines the advantage of the properties of polymer (high molecular weight and higher solubility) with the formation of inclusion complex with cyclodextrin. This justifies the superiority of polymerized cyclodextrin over parent cyclodextrin and some other chemically modified and non-polymerized derivatives. The use of polymerized cyclodextrin in various fields like biomedical, pharmaceutical and gene delivery is increasing day-by-day. ß-Cyclodextrin-epichlorohydrin polymer is a high molecular weight compound, which acts as an effective drug carrier for enhancing the solubility and oral bioavailability of drugs along with the increase in therapeutic efficiency. The future panorama of polymerized cyclodextrins is quite bright as they can serve as useful multifunctional tools for pharmaceutical scientists to develop and optimize drug delivery through various routes. Also, no information concerning the regulatory status and toxicity of polymerized cyclodextrins is available. So, there is a need to focus on these critical issues for resolving the problems associated with the development and commercialization of drug products.