Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity
Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/1/80 |
| _version_ | 1797437840484728832 |
|---|---|
| author | Mohamed F. Zaky Mohamed A. Megahed Taha M. Hammady Shadeed Gad Mamdouh Mostafa Ghorab Khalid M. El-Say |
| author_facet | Mohamed F. Zaky Mohamed A. Megahed Taha M. Hammady Shadeed Gad Mamdouh Mostafa Ghorab Khalid M. El-Say |
| author_sort | Mohamed F. Zaky |
| collection | DOAJ |
| description | Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y<sub>1</sub>), zeta potential (Y<sub>2</sub>), and entrapment efficiency percent (Y<sub>3</sub>) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y<sub>1</sub>, Y<sub>2</sub>, and Y<sub>3</sub>, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and C<sub>max</sub> by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity. |
| first_indexed | 2024-03-09T11:28:27Z |
| format | Article |
| id | doaj.art-6405b0c884324bf09cbab0b622bee553 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:28:27Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6405b0c884324bf09cbab0b622bee5532023-11-30T23:57:22ZengMDPI AGPharmaceutics1999-49232022-12-011518010.3390/pharmaceutics15010080Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant ActivityMohamed F. Zaky0Mohamed A. Megahed1Taha M. Hammady2Shadeed Gad3Mamdouh Mostafa Ghorab4Khalid M. El-Say5Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, EgyptDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaApixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y<sub>1</sub>), zeta potential (Y<sub>2</sub>), and entrapment efficiency percent (Y<sub>3</sub>) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y<sub>1</sub>, Y<sub>2</sub>, and Y<sub>3</sub>, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and C<sub>max</sub> by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity.https://www.mdpi.com/1999-4923/15/1/80apixabanvenous thromboembolismnanostructured lipid carrierbox–behnken designindustrial developmentin vivo pharmacokinetic |
| spellingShingle | Mohamed F. Zaky Mohamed A. Megahed Taha M. Hammady Shadeed Gad Mamdouh Mostafa Ghorab Khalid M. El-Say Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity Pharmaceutics apixaban venous thromboembolism nanostructured lipid carrier box–behnken design industrial development in vivo pharmacokinetic |
| title | Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity |
| title_full | Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity |
| title_fullStr | Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity |
| title_full_unstemmed | Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity |
| title_short | Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity |
| title_sort | tailoring apixaban in nanostructured lipid carrier enhancing its oral bioavailability and anticoagulant activity |
| topic | apixaban venous thromboembolism nanostructured lipid carrier box–behnken design industrial development in vivo pharmacokinetic |
| url | https://www.mdpi.com/1999-4923/15/1/80 |
| work_keys_str_mv | AT mohamedfzaky tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity AT mohamedamegahed tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity AT tahamhammady tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity AT shadeedgad tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity AT mamdouhmostafaghorab tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity AT khalidmelsay tailoringapixabaninnanostructuredlipidcarrierenhancingitsoralbioavailabilityandanticoagulantactivity |