Novel Meta-iodobenzylguanidine and Etoposide Complex: Physicochemical Characterization and Mathematical Modeling of Anticancer Activity.

It is hypothesized that meta-iodobenzylguanidine (MIBG) complexation with etoposide (VP-16) will improve drug solubility and specificity towards BE(2)C neuroblastoma (NB) cells, 90% of which are known to be MIBG avid. After MIBG and VP-16 interaction, the dry complex was analyzed for crystalline structure, surface morphology, solubility, and size distribution by X-ray powder diffraction (P-XRD), scanning electron microscopy (SEM), infrared (FTIR) and UV spectroscopy, and dynamic light scattering. After exposure to the complex, the cell viability and decay rates were assessed by the MTS assay and estimated using exponential decay models (EDM). Multi-factorial ANOVA and an independent t-test were used to assess for cell viability and solubility data, respectively. The resulting (1: 3 w/w) VP-16: MIBG complex had a mean diameter and zeta potential of 458.5 nm and 0.951 mV, respectively. It dramatically increased the drug apparent water solubility (~ 12-folds). This was ascribed to the formation of a VP-16/MIBG nanocrystalline state mainly governed by cation-π interactions, evidenced by FTIR, SEM, and P-XRD data following the complexation. The EDM relating percent cell viability to drug concentration yielded an excellent fit (r2 > 0.95) and enabled to estimate the IC50 values of both native drug and its complex: 6.2 µM and 5.23 µM, respectively (indicating a conservation of drug anticancer activity). The statistical results were consistent with those of the exponential decay models, indicating that MIBG does not inhibit the anticancer activity of VP-16. This study indicates that the VP-16/MIBG complexation improves VP-16 solubility without antagonizing its anticancer activity. Moreover, the efficiency of the EDM for drug IC50 estimation provides alternative mathematical method for such in vitro cytotoxicity studies.

Engineering fast dissolving sodium acetate mediated crystalline solid dispersion of docetaxel.

It is hypothesized that a novel crystalline solid dispersion (CSD) of docetaxel (C-DXT) can be engineered by dispersing native docetaxel (DXT, a BCS class II drug) in sodium acetate crystal (SA). DXT is dissolved in glacial acetic/SA solution and freeze-dried. The resulting C-DXT is characterized by differential scanning calorimetry (DSC), powder X-ray analysis (PXRD), LC-MS/MS, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Quartz crystal microbalance with dissipation monitoring (QCM-D) and dynamic light scattering (DLS). Its cytotoxicity on model cancerous (MCF-7, MDA-MB-468) and normal breast cells (MCF-10A) is assessed by MTS assay. SEM/TEM data and the absence of the characteristics peaks of DXT on the DSC curve (at 193.4 °C) and the XRD scan (at 2θ = 15.31 °C and 23.04 °C) confirm the presence of C-DXT in SA. The LC-MS/MS data indicates the chemical stability of DXT. The yield and C-DXT loading are 95.2% and 6.52% w/w, respectively. The C-DXT rapidly forms an aqueous non-rigid nanosuspension with a faster drug dissolution rate compared to native DXT. Unlike, control Tween 80/ethanol, SA is noncytotoxic to normal cells. However, C-DXT's cytotoxicity is time and dose dependent for all diseased cells. This unique CSD process might be applicable to other hydrophobic bioactive agents to enhance their safety and efficacy.