Physicochemical characterization and anticancer activity evaluation of βcyclodextrin-gemini based nano-delivery systems
Date
2015-07-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Doctoral
Abstract
Lipophilic anticancer agents such as curcumin analogs have low water solubility and low in vivo bioavailability. βCyclodextrin-gemini surfactant is a novel drug delivery agent synthesized by attachment of βcyclodextrin to cationic gemini surfactants. βCyclodextrin can accommodate lipophilic guest molecules in its cavity and form host/guest inclusion complexes. The amphiphilic nature of the gemini surfactants enable them to self-assemble into nano-structures. Herein, physicochemical properties of the delivery agent, free βcyclodextrin-gemini surfactant and the complexes composed of a curcumin analog (NC 2067) and βcyclodextrin or βcyclodextrin-gemini surfactant were evaluated to comprehend the geometry of the host/guest interactions and the nano-structural arrangements of the βcyclodextrin-gemini surfactant-based formulations. Anticancer activity and cell death mechanisms associated with NC 2067 in the presence of the delivery agent were evaluated.
The physicochemical characterization of the host/guest complexes was performed using various synchrotron and non-synchrotron based techniques such as powder X-ray diffraction, Fourier transform infrared spectroscopy and thermogravimetric analysis. 1D and 2D NMR techniques, namely rotating frame Overhauser effect spectroscopy, were employed to characterize the structural properties of the free βcyclodextrin gemini surfactant and NC 2067 complexes with βcyclodextrin or βcyclodextrin-gemini surfactant comprehensively. Size measurements and small and wide-angle X-ray scattering studies employed to study the nanoparticulate characteristics of the βcyclodextrin-gemini surfactant-based formulations. Cell viability analysis and flow cytometry assays were employed to appraise the cell death induction in A375 melanoma cells.
It was found that NC 2067 is able to form complexes with βcyclodextrin at 1:2 mole ratio through the interactions of the aromatic moieties with the βcyclodextrin cavity. Moreover, in βcyclodextrin-gemini surfactant, the hydrocarbon tail of the gemini moiety was inserted into βcyclodextrin through intra-molecular interactions. NC 2067 formed complexes with βcyclodextrin-gemini surfactant and retained its ability to kill selected cancer cells and showed proapoptotic activity. However, it was not able to alter the self-inclusion of the βcyclodextrin-gemini surfactant significantly.
The physicochemical assessment of the interaction of a novel gemini surfactant-based βcyclodextrin delivery agent with a model cytotoxic agent for the first time and evaluation of the βcyclodextrin-gemini surfactant-based formulations will aid to design and develop more efficient anticancer drug delivery systems.
Description
Keywords
delivery agent, inclusion complex, supramolecular arrangement, synchrotron
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Pharmacy and Nutrition
Program
Pharmacy