DZ-BAU2021-14N AS NOVEL PYRAZOLOPYRIDINE NANOCRYSTALS: APPRAISAL OF ANTICANCER ACTIVITY AGAINST HCT-116 AND HT-29 COLORECTAL CANCER CELL LINES

Mentioning DZ-BAU2021-14 (C19H17N5O2,347.370 g/mol) developed in BAU Labs, its promising preliminary antitumor effect nominated it to be selected as a lead antiproliferative compound against colorectal cancer cell lines owing to its proved Cyclin Dependent Kinase 2 (CDK2) inhibition (Kassem et al., 2021). Solving many problems restricting traditional cancer therapy, nanotechnology is offering safety margins and targeted delivery of poorly soluble drug. The potential effect of this compound was combined with the advantages of nanotechnology, precisely nanocrystals to achieve better antiproliferative and hopeful less cytotoxic patterns. The nanocrystals DZ-BAU2021-14N were prepared by an antisolvent precipitation technique using Poloxamer 407 and Cremophor® RH 40 as stabilizers. The nanocrystals were obtained with a nanometric particle size (89.80 ± 11.2 nm) and a negative zeta potential (-32.6 ± 0.50 mV) and were stable at 4 ± 0.5°C with no significant change in particle size or zeta potential. The anticancer activity of DZ-BAU2021-14 and DZ-BAU2021-14N were assessed. Their antiproliferative effects against colorectal cancer cell lines HCT-116 and HT-29 were studied via viability assay. In addition, their cytotoxic effects on non-tumorigenic cell lines NCM-460D were evaluated and respective IC50 values were determined. Different responses were obtained; DZ-BAU2021-14N provided lower IC50 on HCT-116 compared to the free drug DZ-BAU2021-14 (27 and 22 µM, respectively). The safety profile of the free drug was reflected by its IC50 on NCM-460D of 200µM while that of drug nanocrystals showed relative cytotoxicity with IC50 of 33µM, and this requires further investigation to study this response

Application of Box-Behnken Design in the Preparation, Optimization, and In-Vivo Pharmacokinetic Evaluation of Oral Tadalafil-Loaded Niosomal Film

Benign prostatic hyperplasia (BPH) affects about 90% of men whose ages are over 65. Tadalafil, a selective PDE-5 inhibitor, was approved by FDA for BPH, however, its poor aqueous solubility and bioavailability are considered major drawbacks. This work intended to develop and evaluate oral fast dissolving film containing tadalafil-loaded niosomes for those who cannot receive the oral dosage form. Niosomes were statistically optimized by Box-Behnken experimental design and loaded into a polymeric oral film. Niosomes were assessed for their vesicular size, uniformity, and zeta potential. The thickness, content uniformity, folding endurance, tensile strength, disintegration time, and surface morphology were evaluated for the prepared polymeric film. The optimized niosomes revealed high entrapment efficiency (99.78 ± 2.132%) and the film was smooth with good flexibility and convenient thickness (110 ± 10 µm). A fast release of tadalafil was achieved within 5 min significantly faster than the niosomes-free drug film. The in-vivo bioavailability in rats established that the optimized niosomal film enhanced tadalafil systemic absorption, with higher peak concentration (Cmax = 0.63 ± 0.03 µg/mL), shorter Tmax value (0.66-fold), and relative bioavailability of 118.4% compared to the marketed tablet. These results propose that the oral film of tadalafil-loaded niosomes is a suitable therapeutic application that can be passed with ease to geriatric patients who suffer from BPH