Inclusion Complexes of Melphalan with Gemini-Conjugated β-Cyclodextrin: Physicochemical Properties and Chemotherapeutic Efficacy in In-Vitro Tumor Models
| Autor: | Ronald E. Verrall, Abdalla H. Karoyo, Waleed Mohammed-Saeid, Ildiko Badea, Lee D. Wilson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pharmaceutical Science
Excipient lcsh:RS1-441 drug-resistant melanoma 02 engineering and technology Conjugated system Article lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine Dynamic light scattering Pulmonary surfactant hemic and lymphatic diseases medicine Solubility neoplasms chemistry.chemical_classification Cyclodextrin Chemistry ROESY NMR spectroscopy 3D spheroid 021001 nanoscience & nanotechnology Combinatorial chemistry 3. Good health melphalan 030220 oncology & carcinogenesis cationic gemini surfactant 0210 nano-technology Two-dimensional nuclear magnetic resonance spectroscopy inclusion complex Conjugate medicine.drug |
| Zdroj: | Pharmaceutics Volume 11 Issue 9 Pharmaceutics, Vol 11, Iss 9, p 427 (2019) |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics11090427 |
| Popis: | &beta cyclodextrin (&beta CD) has been widely explored as an excipient for pharmaceuticals and nutraceuticals as it forms stable host&ndash guest inclusion complexes and enhances the solubility of poorly soluble active agents. To enhance intracellular drug delivery, &beta CD was chemically conjugated to an 18-carbon chain cationic gemini surfactant which undergoes self-assembly to form nanoscale complexes. The novel gemini surfactant-modified &beta CD carrier host (hereafter referred to as 18:1&beta CDg) was designed to combine the solubilization and encapsulation capacity of the &beta CD 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 18:1&beta CDg-Mel host&ndash 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 18:1&beta CDg-Mel inclusion complexes at the 2:1 host&ndash guest mole ratio whereas, host&ndash drug interaction was attenuated at greater 18:1&beta CDg 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 18:1&beta CDg-Mel complex showed significant enhancement in the chemotherapeutic efficacy of Mel with 2&ndash 3-fold decrease in Mel half maximal inhibitory concentration (IC50) values. The findings demonstrate the potential applicability of the 18:1&beta CDg delivery system as a safe and efficient carrier for a poorly soluble chemotherapeutic in melanoma therapy. |
| Databáze: | OpenAIRE |
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