A ¹H NMR Study of Host/Guest Supramolecular Complexes of a Curcumin Analogue with β-Cyclodextrin and a β-Cyclodextrin-Conjugated Gemini Surfactant

Abstract

Host systems based on β-cyclodextrin (βCD) were employed as pharmaceutical carriers to encapsulate a poorly soluble drug, curcumin analogue (NC 2067), in order to increase its water solubility. βCD was chemically conjugated with an amphiphilic gemini surfactant with the ability to self-assemble and to form nanoscale supramolecular structures. The conjugated molecule, βCDgemini surfactant (βCDg), was shown to be a promising drug delivery agent. In this report, its physicochemical properties were assessed in aqueous solution using 1D and 2D 1H NMR spectroscopy. The results showed that the apolar hydrocarbon domain of the gemini surfactant was self-included within the βCD internal cavity. The host/guest complexes composed of native βCD or βCDg with NC 2067 were examined using 1D/2D ROESY NMR methods. The stoichiometry of βCD/NC 2067 complex was estimated using Job's method via 1H NMR spectroscopy. The binding geometry of NC 2067 within βCD was proposed using molecular docking and further supported by 1D and 2D ROESY NMR results. Addition of NC 2067 to βCDg revealed minimal changes to the overall structure of the βCDg system, in agreement with the formation of a βCDg/NC 2067 ternary complex.

Rapid and simple flow injection analysis tandem mass spectrometric method for the quantification of melphalan in a lipid‐based drug delivery system

“…We propose that at [2:1] 18:1βCDg/Mel molar ratio, two 18:1βCDg molecules encapsulate one melphalan molecule forming stable inclusion complexes leading to the higher solubilizing effect. This result is in support of the previous model proposed by our group …”

“…This property of β‐CD has been employed widely in the pharmaceutical industry to increase the aqueous solubility of hydrophobic moieties with several β‐CD‐based formulations available on the market, such as VFEND ® (voriconazole, an azole antifungal agent) and NEXTERONE ® (amiodarone, an antiarrhythmic medication) among others, and hundred in clinical trials . Previously, our group reported that the βCD‐modified gemini surfactant (12 β CDgemini) is capable of forming guest/host complexes with a hydrophobic anticancer molecule …”

“…The resulting conjugate, 18:1‐7NβCD‐18:1 (18:1βCDg) (Figure C), combines the encapsulation properties of β‐CD and the cell‐penetrating ability of cationic gemini surfactants . This novel drug delivery system can incorporate lipophilic drugs, such as melphalan, into the β‐CD moiety and form a nano‐platform .…”

Evaluation of β-cyclodextrin-modified gemini surfactant-based delivery systems in melanoma models

“…This increase could be due to the fact that Mel is associated with the hydrophobic cavity of the CDgemini, 22 thus protecting it from protein binding in the cell culture milieu 33 and making it more available for cellular uptake. Alternatively, the nanoparticles could carry several molecules and be released, intracellularly, from the endocytosed nanoparticles.…”

“…This ratio was selected based on the previous studies of the encapsulation of poorly soluble compounds in CDgemini. [20][21][22] The solvents were removed by speed vacuum, and the nanoparticles were re-suspended either in water or in a 0.5% methylcellulose (Medisca, Montreal, QC, Canada) gel.…”