Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer
| Autor: | Ahmed S. G. Srag El-Din, Yasser M. Moustafa, Mohamed Salem, Ahmed R. Gardouh, Shadeed Gad |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Starch
starch nanoparticles pancreatic cancer Pharmaceutical Science Biological Availability Antineoplastic Agents Dosage form chemistry.chemical_compound Mice Differential scanning calorimetry Drug Discovery Zeta potential Animals Fourier transform infrared spectroscopy Solubility ADME Original Research Pharmacology Drug Design Development and Therapy thienopyrimidine derivative solid Ehrlich carcinoma Bioavailability Pancreatic Neoplasms Drug Liberation Pyrimidines chemistry Nanoparticles Female Nuclear chemistry |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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