Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer.

PURPOSE: This research aimed to improve water solubility and oral bioavailability of a newly synthesized thienopyrimidine derivative (TPD) with anti-pancreatic cancer activity by loading on starch nanoparticles (SNPs). METHODS: TPD was synthesized, purified and its ADME behavior was predicted using Swiss ADME software. A UV spectroscopy method was developed and validated to measure TPD concentration at various dosage forms. SNPs loaded with TPD (SNPs-TPD) were prepared, characterized for particle size, polydispersity index, zeta potential, transmission electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), entrapment efficiency, in-vitro release, and in-vivo animal study. RESULTS: The Swiss ADME results showed that TPD can be administered orally; however, it has low oral bioavailability (0.55) and poor water solubility. The significant regression coefficient of the calibration curve (r2 = 0.9995), the precision (%RSD < 0.5%) and the accuracy (99.46-101.72%) confirmed the efficacy of the developed UV method. SNPs-TPD had a spherical monodispersed (PDI= 0.12) shape, nanoparticle size (22.98 ± 4.23) and good stability (-21 ± 4.72 mV). Moreover, FT-IR and DSC revealed changes in the physicochemical structure of starch resulting in SNPs formation. The entrapment efficiency was 97% ± 0.45%, and the in-vitro release showed that the SNPs enhanced the solubility of the TPD. The in-vivo animal study and histopathology showed that SNPs enhanced the oral bioavailability of TPD against solid Ehrlich carcinoma. CONCLUSION: SNPs-TPD were superior in drug solubility and oral bioavailability than those obtained from TPD suspension.

Effect of novel synthetic evodiamine analogue on sexual behavior in male rats.

Currently phosphodiestrase5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction. Drugs such as sildenafil and tadalafil are available as PDE5 inhibitors which are potent and reversible but lack selectivity with side effects such as headache, facial flushing, dyspepsia, and visual disturbances. We herein report for the first time novel condensed thienopyrimidines as evodiamine analogue and their effect on sexual behavior in male rats hitherto unreported. Novel synthetic evodiamine significantly showed improvement in male rat copulatory behavior. The test compound MKAC9 could be of promising importance in the treatment of sexual disorders like desire disorder or erectile dysfunction.FigureEvodiamine analogue on sexual behavior in male rats.