Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background:Castrate circumstances brought on by therapy give rise to castrationresistant prostate cancer (CRPC), which thereafter develops androgen receptor (AR) resistance. AR inhibitors are frequently used to obstruct AR translocation in cells that overexpress AR and slow the progression of cancer by reducing the number of AR receptors that are accessible. In comparison to Bicalutamide, a first-generation AR inhibitor, the hydrophobic drug Enzalutamide has demonstrated higher effectiveness. We investigate Enzalutamide as a viable option for the formation of self-assembly complexes because AR downregulation is still the major treatment for CRPC.
Methods:Enz-loaded self-assembly complexes (enz-β-CD) formulation was developed using solvent evaporatin method utilizing β-cyclodextrin (β-CD) as a solubilizer, which has a welldocumented safety profile and FDA approval. The inclusion complex formation has been confirmed from dynamic light scattering (DLS), Fourier-transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR) spectral analysis, respectively. The cellular internalization capacity of this formulation was evaluated using flow cytometry and fluorescent microscopy. The therapeutic efficacy of enz-β-CD self-assembly complexes was evaluated using clinically relevant PC cell lines (C4-2B, and 22-RV1) through cell proliferation and colony formation assays. Caco2 permiability assay was used to test the suitability of compound for oral dosing.
Results: Our DLS, DSC, XRD, FTIR, and NMR studies demonstrated that Enz was entrapped in the inner cavity of β-CD, and the inclusion complex formed in an amorphous state. The particle size of the inclusion complex was found less than 100 nm, while zeta potential and PDI were −7.6 mV and 0.2, respectively. Moreover, inclusion complexes have the characteristic structure of an adduct, in which one compound (Enz) guest molecule, is enclosed to the host molecule i.e. β-CD. Interestingly the guest molecule is situated in the cavity of the host without significantly affecting the host framework structure. The flow cytometry and fluorescence microscopy analysis confirmed a dose-dependant cellular uptake in PC cells. The CCK-8 assay confirms that enz-β-CD self-assembly complexes exhibited anticancer effects in C42B and 22RV1 cells, like bare Enz. A similar clonogenic potential was noticed with the enz-β-CD selfassembly complexes.The permeability assay showed the drug efflux that would allow for intestinal permiability of the drug.
Conclusions: Based on our findings, the free medication does not possess the Enz-Beta cyclodextrin formulation's improved anti-cancer characteristics. For the successful therapy of castrationresistant prostate cancer (CRPC), this new inclusion complex shows promise.
Academic/Professional Position
Graduate Student
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Kolli, Meghana; Tiwari, Rahul; Chauhan, Subhash C.; Zhang, Yonghong; Chauhan, Neeraj; M, Alba C.; and Yallapu, Murali, "β-cyclodextrin-enzalutamide self-assembly complexes for prostate cancer therapy" (2024). Research Symposium. 72.
https://scholarworks.utrgv.edu/somrs/2024/posters/72
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Medicine and Health Sciences Commons
β-cyclodextrin-enzalutamide self-assembly complexes for prostate cancer therapy
Background:Castrate circumstances brought on by therapy give rise to castrationresistant prostate cancer (CRPC), which thereafter develops androgen receptor (AR) resistance. AR inhibitors are frequently used to obstruct AR translocation in cells that overexpress AR and slow the progression of cancer by reducing the number of AR receptors that are accessible. In comparison to Bicalutamide, a first-generation AR inhibitor, the hydrophobic drug Enzalutamide has demonstrated higher effectiveness. We investigate Enzalutamide as a viable option for the formation of self-assembly complexes because AR downregulation is still the major treatment for CRPC.
Methods:Enz-loaded self-assembly complexes (enz-β-CD) formulation was developed using solvent evaporatin method utilizing β-cyclodextrin (β-CD) as a solubilizer, which has a welldocumented safety profile and FDA approval. The inclusion complex formation has been confirmed from dynamic light scattering (DLS), Fourier-transformed infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR) spectral analysis, respectively. The cellular internalization capacity of this formulation was evaluated using flow cytometry and fluorescent microscopy. The therapeutic efficacy of enz-β-CD self-assembly complexes was evaluated using clinically relevant PC cell lines (C4-2B, and 22-RV1) through cell proliferation and colony formation assays. Caco2 permiability assay was used to test the suitability of compound for oral dosing.
Results: Our DLS, DSC, XRD, FTIR, and NMR studies demonstrated that Enz was entrapped in the inner cavity of β-CD, and the inclusion complex formed in an amorphous state. The particle size of the inclusion complex was found less than 100 nm, while zeta potential and PDI were −7.6 mV and 0.2, respectively. Moreover, inclusion complexes have the characteristic structure of an adduct, in which one compound (Enz) guest molecule, is enclosed to the host molecule i.e. β-CD. Interestingly the guest molecule is situated in the cavity of the host without significantly affecting the host framework structure. The flow cytometry and fluorescence microscopy analysis confirmed a dose-dependant cellular uptake in PC cells. The CCK-8 assay confirms that enz-β-CD self-assembly complexes exhibited anticancer effects in C42B and 22RV1 cells, like bare Enz. A similar clonogenic potential was noticed with the enz-β-CD selfassembly complexes.The permeability assay showed the drug efflux that would allow for intestinal permiability of the drug.
Conclusions: Based on our findings, the free medication does not possess the Enz-Beta cyclodextrin formulation's improved anti-cancer characteristics. For the successful therapy of castrationresistant prostate cancer (CRPC), this new inclusion complex shows promise.