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

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

Publication date: Aug 22, 2019

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 H 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 (IC) 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.

Concepts Keywords
Assembly Carbon chain
Carbon Carrier host
Cationic Melanoma therapy
Chemotherapeutic Chemotherapeutic agent melanoma
Chemotherapeutic Agent Tumor
Cyclodextrin Resistant melanoma
DLS Drug resistant melanoma
Drug Delivery Physical sciences
Drug Interaction Natural sciences
Dynamic Light Scattering Chemistry
Encapsulation Macrocycles
Excipient Polysaccharides
Gemini Specialty drugs
Hydrophobic Cyclodextrin
Intracellular Starch
Macrocycle Melphalan
Melanoma Chemotherapy
Melphalan Solubility
Mole Nutraceuticals
Monolayer Spectroscopy
Nanoscale Drug delivery
NMR
NMR Spectroscopy
Nutraceuticals
Pharmaceuticals
Pharmaceutics
Solubility
Spheroid
Surfactant

Semantics

Type Source Name
disease MESH drug interaction
gene UNIPROT TNFSF14
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT RAB8A
drug DRUGBANK Honey
drug DRUGBANK Activated charcoal
disease MESH Tumor
drug DRUGBANK Melphalan

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