Drug Design, Development and Therapy (Jul 2021)
Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer
Abstract
Ahmed R Gardouh,1,2 Ahmed SG Srag El-Din,3 Mohamed SH Salem,4,5 Yasser Moustafa,6,7 Shadeed Gad1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; 2Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid, 21110, Jordan; 3Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science & Technology, Gamasa City, Egypt; 4Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt; 5The Institute of Scientific and Industrial Research (ISIR), Osaka University, Ibaraki-shi, Osaka, 567-0047, Japan; 6Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; 7Department of Pharmacology and Toxicology, Faculty of Pharmacy, Badr University in Cairo, Badr City, Cairo, EgyptCorrespondence: Ahmed SG Srag El-DinDepartment of Pharmaceutics, Faculty of Pharmacy, Delta University for Science & Technology, International Coastal Road, Gamasa City, Mansoura, Dakhliya, 35712, EgyptTel +201008966506Email [email protected]: 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.Keywords: thienopyrimidine derivative, starch nanoparticles, pancreatic cancer, solid Ehrlich carcinoma
