Enhancement of the dissolution and in-vitro activity of a new antineoplastic agent.

The cell-surface molecule CD44 plays a major role in the regulation of cancer stem cells. The CD44 inhibitor compound N'-(1-dimethylaminomethyl-2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazide (OYB), anticancer agent is practically insoluble in water. Hence, the solid dispersion (SD) technique was used for enhancing the dissolution of OYB. The SD of OYB was achieved using OYB:poloxamer 188 (1:7) via the fusion method. The anticancer activities of the free-OYB solution and the SD formulation (OYB-SD) were investigated in-vitro. The dissolution rate of OYB-SD (1:7) increased by 2-fold compared with the untreated drug (51.52-100% at pH 1.2 and 8.25-19.15% at pH 7 buffer). In addition, OYB-SD afforded 3-folds cytotoxic effect, against LoVo cells, compared to the untreated compound (IC50 4.72 ± 0.57 and 13.97 ± 0.90 µg/ml, respectively) and against HepG2 (∼3-fold) (4.98 ± 0.368 and 13.85 ± 1.82 µg/ml, respectively) and MCF-7 (1.4-fold) cells (15.20 ± 0.20 and 21.12 ± 0.51 µg/ml, respectively), and enhanced the apoptotic potential in LoVo cells compared with free-OYB. The improved cytotoxic activity of the drug might be attributable to the enhanced dissolution of OYB.

PEGylated SLN as a Promising Approach for Lymphatic Delivery of Gefitinib to Lung Cancer.

Purpose: The present study aimed to develop gefitinib-loaded solid lipid nanoparticles (GEF-SLN), and GEF-loaded PEGylated SLN (GEF-P-SLN) for targeting metastatic lung cancer through the lymphatic system. Methods: The prepared SLNs were characterized in terms of physicochemical properties, entrapment efficiency, and in-vitro release. Furthermore, ex-vivo permeability was investigated using the rabbit intestine. Cytotoxicity and apoptotic effects were studied against A549 cell lines as a model for lung cancer. Results: The present results revealed that the particle size and polydispersity index of the prepared formulations range from 114 to 310 nm and 0.066 to 0.350, respectively, with negative zeta-potential (-14 to -27.6). Additionally, SLN and P-SLN showed remarkable entrapment efficiency above 89% and exhibited sustained-release profiles. The permeability study showed that GEF-SLN and GEF-P-SLN enhanced the permeability of GEF by 1.71 and 2.64-fold, respectively, compared with GEF suspension. Cytotoxicity showed that IC50 of pure GEF was 3.5 µg/mL, which decreased to 1.95 and 1.8 µg/mL for GEF-SLN and GEF-P-SLN, respectively. Finally, the apoptotic study revealed that GEF-P-SLN decreased the number of living cells from 49.47 to 3.43 when compared with pure GEF. Conclusion: These results concluded that GEF-P-SLN is a promising approach to improving the therapeutic outcomes of GEF in the treatment of metastatic lung cancer.

Separation of Levofloxacin from Industry Effluents Using Novel Magnetic Nanocomposite and Membranes Hybrid Processes.

Magnetic carbon nanocomposite (MCN) was synthesized from waste biomass precursor, pineapple. The prepared adsorbent was characterized using different instrumental techniques and was used to remove levofloxacin (LEV) from effluents. The maximum sorption of LEV was observed at pH 7. Pseudo-2nd-order (PSO) kinetic was found to be the best model that fits well the adsorption kinetics data. For Langmuir adsorption isotherm, the R2 value was higher as compared with other isotherms. The Van't Hoff equation was used for thermodynamic parameters determinations. ΔS° (standard entropy) was positive and ΔG° (standard Gibb's free energy) was negative: -0.37, -1.81, and -3.73 kJmol-1 corresponding to 25, 40, and 60°C. The negative values of ΔG° at different temperatures stipulate that the adsorption of LEV was spontaneous in nature and adsorbent has a considerable affinity for LEV molecules. The MCN was then utilized in hybrid way by connecting with ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO) membranes in series and as a result enhanced permeate fluxes were observed. The percent retention of LEV molecules was lower with UF membrane and with NF it was 96%, while it was 100% with RO. For MCN/UF and MCN/NF systems, improvement in % retention was recorded.