In situ evaluation of the impact of metformin or verapamil coadministration with vildagliptin on its regional absorption from the rabbit’s intestine Ahmed M. Elmeniar, Mohamed A. Osman, Sanaa A. El‐Gizawy, Dimple Modi, Nitin B. Charbe, et al. Biopharmaceutics and Drug Disposition, 2024 This research aims to identify regional differences in vildagliptin absorption across the intestinal membrane. Furthermore, it was to investigate the effect of verapamil or metformin on vildagliptin absorptive clearance. The study utilized an in situ rabbit intestinal perfusion technique to determine vildagliptin oral absorption from duodenum, jejunum, ileum, and ascending colon. This was conducted both with and without perfusion of metformin or verapamil. The findings revealed that the vildagliptin absorptive clearance per unit length varied by site and was in the order as follows: ileum < jejunum < duodenum < ascending colon, implying that P‐gp is significant in the reduction of vildagliptin absorption. Also, the arrangement cannot reverse intestinal P‐gp, but the observations suggest that P‐gp is significant in reducing vildagliptin absorption. Verapamil co‐perfusion significantly increased the vildagliptin absorptive clearance by 2.4 and 3.2 fold through the jejunum and ileum, respectively. Metformin co‐administration showed a non‐significant decrease in vildagliptin absorptive clearance through all tested segments. Vildagliptin absorption was site‐dependent and may be related to the intestinal P‐glycoprotein content. This may aid in understanding the important elements that influence vildagliptin absorption, besides drug–drug interactions that can occur in type 2 diabetic patients taking vildagliptin in conjunction with other drugs that can modify the P‐glycoprotein level.
Lactosylated Chitosan Nanoparticles Potentiate the Anticancer Effects of Telmisartan In Vitro and in a N-Nitrosodiethylamine-Induced Mice Model of Hepatocellular Carcinoma Mohamed Nasr, Ahmed Y. Kira, Sameh Saber, Ebtessam A. Essa, Sanaa A. El-Gizawy Molecular Pharmaceutics, 2023 Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Telmisartan (TLM), a BSC class II drug, has been reported to have antiproliferative activity in HCC. However, its therapeutic activity is limited by poor bioavailability and unpredictable distribution. This work aimed to enhance TLM's liver uptake for HCC management through passive and active targeting pathways utilizing chitosan nanoparticles decorated with lactose (LCH NPs) as a delivery system. In vitro cell cytotoxicity and cellular uptake studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced the antiproliferative activity and cellular uptake percentage of TLM. In vivo bioavailability and liver biodistribution studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced TLM concentrations in plasma and the liver. The relative liver uptake of TLM from TLM-LCH NPs was 2-fold higher than that of unmodified NPs and 5-fold higher than that of plain TLM suspension. In vivo studies of a N-nitrosodiethylamine-induced HCC model revealed that administration of TLM through LCH NPs improved liver histology and resulted in lower serum alpha-fetoprotein (AFP), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) levels, and liver weight index compared to plain TLM and TLM-loaded unmodified NPs. These results reflected the high potentiality of LCH NPs as a liver-targeted delivery system for TLM in the treatment of HCC.
Application of Design of Experiment in the Optimization of Apixaban-Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluation Safaa E. Ramadan, Sanaa A. El-Gizawy, Mohamed A. Osman, Mona F. Arafa AAPS Pharmscitech, 2023 Solid lipid nanoparticles (SLnPs) are usually utilized as lipid-based formulations for enhancing oral bioavailability of BCS class IV drugs. Accordingly, the objective of this work was to investigate the effect of formulation and processing variables on the properties of the developed SLnPs for oral delivery of apixaban. Randomized full factorial design (24) was employed for optimization of SLnPs. With two levels for each independent variable, four factors comprising both formulations and processing factors were chosen: the GMS content (A), the Tween 80 content (B), the homogenization time (C), and the content of poloxamer 188 used (D). The modified hot homogenization and sonication method was employed in the formulation of solid lipid nanoparticles loaded with apixaban (APX-SLnPs). The size of APX-SLnPs formulations was measured to lie between 116.7 and 1866 nm, polydispersity index ranged from 0.385 to 1, and zeta potential was discovered to be in the range of − 12.6 to − 38.6 mV. The entrapping efficiency of APX-SLnPs formulations was found to be in the range of 22.8 to 96.7%. The optimized formulation was evaluated in vivo after oral administration to rats. Oral administration of APX-SLnPs resulted in significant prolongation in bleeding time compared with both positive and negative control. This indicates the ability of this system to enhance drug therapeutic effect either by increasing intestinal absorption or trans-lymphatic transport. So, this study highlighted the capability of SLnPs to boost the pharmacological effect of apixaban. Graphical Abstract
Telmisartan-Loaded Lactosylated Chitosan Nanoparticles as a Liver Specific Delivery System: Synthesis, Optimization and Targeting Efficiency Mohamed Nasr, Ahmed Y. Kira, Sameh Saber, Ebtessam A. Essa, Sanaa A. El-Gizawy AAPS Pharmscitech, 2023 Hepatocellular carcinoma (HCC) has a significant economic impact and a high mortality rate. Telmisartan (TLM) is a potential therapy for HCC, but it has a limited scope in drug delivery due to unpredictable distribution and poor bioavailability. The objective of this study was to prepare, design, and in vitro evaluate lactose-modified chitosan nanoparticles (LCH NPs) as a liver-targeted nanocarrier for TLM with the potential to offer a promising HCC therapy. The combination of chitosan with lactose was successfully attained using the Maillard reaction. TLM-LCH NPs were prepared, characterized, and optimized with the developed 23 full factorial design. The optimized formulation (F1) was in vitro and in vivo characterized. LCH was synthesized with an acceptable yield of 43.8 ± 0.56%, a lactosylation degree of 14.34%, and a significantly higher aqueous solubility (6.28 ± 0.21 g/L) compared to native chitosan (0.25 ± 0.03 g/L). In vitro characterization demonstrated that, F1 had a particle size of 145.46 ± 0.7 nm, an entrapment efficiency of 90.21 ± 0.28%, and a surface charge of + 27.13 ± 0.21 mV. In vitro TLM release from F1 was most consistent with the Higuchi model and demonstrated significantly higher release at pH 5.5. Moreover, a significantly higher ratio of liver to plasma concentration was observed with TLM-LCH NPs compared to plain TLM and unmodified TLM-NPs. The obtained results nominate TLM-LCH NPs as a promising carrier for enhancing liver targeting of TLM in treatment of HCC. Graphical abstract
Comparative evaluation of the efficiency of the microencapsulation methods to improve the flavor production by Leuconostoc mesenteroides and Streptococcus lactis diacetilactis Research Journal of Pharmaceutical Biological and Chemical Sciences, 2016
