Inclusion Complexes of Melphalan with Gemini-Conjugated β-Cyclodextrin: Physicochemical Properties and Chemotherapeutic Efficacy in In-Vitro Tumor Models

Abstract

β-cyclodextrin (βCD) has been widely explored as an excipient for pharmaceuticals and nutraceuticals as it forms stable host–guest inclusion complexes and enhances the solubility of poorly soluble active agents. To enhance intracellular drug delivery, βCD was chemically conjugated to an 18-carbon chain cationic gemini surfactant which undergoes self-assembly to form nanoscale complexes. The novel gemini surfactant-modified βCD carrier host (hereafter referred to as 18:1βCDg) was designed to combine the solubilization and encapsulation capacity of the βCD macrocycle and the cell-penetrating ability of the gemini surfactant conjugate. Melphalan (Mel), a chemotherapeutic agent for melanoma, was selected as a model for a poorly soluble drug. Characterization of the 18:1βCDg-Mel host–guest complex was carried out using 1D/2D 1H NMR spectroscopy and dynamic light scattering (DLS). The 1D/2D NMR spectral results indicated the formation of stable and well-defined 18:1βCDg-Mel inclusion complexes at the 2:1 host–guest mole ratio; whereas, host–drug interaction was attenuated at greater 18:1βCDg mole ratio due to hydrophobic aggregation that accounts for the reduced Mel solubility. The in vitro evaluations were performed using monolayer, 3D spheroid, and Mel-resistant melanoma cell lines. The 18:1βCDg-Mel complex showed significant enhancement in the chemotherapeutic efficacy of Mel with 2–3-fold decrease in Mel half maximal inhibitory concentration (IC50) values. The findings demonstrate the potential applicability of the 18:1βCDg delivery system as a safe and efficient carrier for a poorly soluble chemotherapeutic in melanoma therapy.

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

“…An inappropriate drug concentration at the tumor site and toxicity complications are the main causes of inadequate chemotherapeutic efficiency [ 1 , 2 ]. Localized delivery is imperative in order to develop efficient treatments for aggressive types of cancer, such as melanoma, ovarian cancer, neuroblastoma, and multiple myeloma, among others [ 3 , 4 , 5 ].…”

“…Melphalan (MPH) and cytoxan (CYT) ( Figure 1 ) are anti-cancer chemotherapy drugs classified as alkylating agents [ 5 , 6 ]. Alkylating agents work by damaging the DNA of cancer cells.…”

β-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery

“…This suggests that MPH might be more aptly sized than CUR to be included in the supramolecular sites of NSs. The encapsulation efficiency and loading capacity values for NSs–CUR and NSs–MPH complexes increased, compared to native β-CD, where the calculated values were 30% (EE%) and 20% (LC%) for β-CD–CUR [ 65 , 73 ], and 70% (EE%) and 61% (LC) for β–CD–MPH [ 74 ].…”

Affinity Effects on the Release of Non-Conventional Antifibrotics from Polymer Depots

“…Previous work has demonstrated the use of modified cyclodextrins and cyclodextrin polymers to deliver poorly soluble drugs [7][8][9]. However, using cyclodextrins (CD) in a different line of work, we sought to provide a sustained delivery of small molecules for longer than their short, diffusion-based half-lives to better match the timeline of fibrosis and wound healing.…”