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

Abstract

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 (r 2 = 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.

New anionic cobalt(III) complexes enable enantioselective synthesis of spiro-fused oxazoline and iodoacetal derivatives

“…Enol ether derivative 1a was selected as the model starting material to investigate its iodocyclization reaction, which can afford spiro-fused oxazoline scaffold 2a , the core structure of many chiral ligands, and biologically active compounds as one of the N -heterocycles ( Banks et al, 2001 ; Heckmann and Bach, 2005 ; Holmes et al, 2005 ; Yadav et al, 2011 ; Bhandari Neupane et al, 2019 ; Bylo et al, 2020 ; Salem et al, 2020 ; Connon et al, 2021 ; Gardouh et al, 2021 ). The reaction of enol ether derivative 1a with N -iodosuccinimide (NIS) was initially examined in the presence of 10 mol% of the sodium salts of anionic chiral cobalt (III) complexes: Λ-( S , S )- 3a and Λ-( S , S )- 3b ( Table 1 ).…”

Development and Evaluation of a Self-Nanoemulsifying Drug Delivery System for Sinapic Acid with Improved Antiviral Efficacy against SARS-CoV-2

“…SA-SNEs were diluted with deionized water and subjected to particle size examination. The average particle size, polydispersity index (PDI), and zeta potential were determined using dynamic light scattering on a Malvern Zetasizer (Malvern Instruments, Malvern, UK) [31].…”

Azithromycin loaded chitosan nanoparticles preparation and in-vitro characterization

“…The chitosan nanoparticles loaded with azithromycin suspension were diluted with deionized water (0.01%, v/v) and the electrical charge of the prepared nanoparticles was measured using a Malvern size distribution analyser (Zeta-sizer, Malvern Instruments, UK) at 25 °C. The refractive index and viscosity of water were 1.330 and 0.89 cp, respectively (Gardouh et al, 2021).…”

“…Nanoparticles as one of the most recent novel drug delivery carriers have been shown to improve drug efficiency via targeting the delivery of drugs, improving the bioavailability and either sustaining the release of the drugs or solubilizing them for systemic delivery. Additional advantage of this novel technology is the lower enzymatic as well as environmental degradation of pharmaceutical active ingredients (Shahira F. El-Menshawe et al, 2017;Gardouh et al, 2021;Ge et al, 2002).…”

“…The main features of nanoparticles, making them ideal candidates for drug delivery, are small size and use of biodegradable materials in their preparation. Indeed the nano-sized character of these particles causes their extravagation through the endothelium in inflammatory sites, epithelium, tumours, or penetrate microcapillaries and consequently allows for efficient uptake by a variety of cell types and selective drug accumulation at target sites (Gardouh et al, 2021;Singh & Lillard Jr, 2009;Sunderland et al, 2006).…”