Nanotheranostics 2023; 7(1):117-127. doi:10.7150/ntno.78102 This issue Cite

Research Paper

Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability

Narendar Dudhipala1,2✉, Swetha Ettireddy2, Ahmed Adel Ali Youssef3, Goverdhan Puchchakayala1,2

1. Department of Pharmaceutics, Vaagdevi Pharmacy College, Warangal, Telangana, India - 506005.
2. Synapse Life Sciences, Warangal, Telangana, India - 506001.
3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, 33516, Egypt.

Citation:
Dudhipala N, Ettireddy S, Youssef AAA, Puchchakayala G. Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics 2023; 7(1):117-127. doi:10.7150/ntno.78102. https://www.ntno.org/v07p0117.htm
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Abstract

Graphic abstract

Background: Irbesartan (IR) is used in the treatment of hypertension, heart failure, and nephropathy in Type II diabetes. IR bioavailability is limited by poor solubility and presystemic metabolism. In our previous investigations, cyclodextrin (HPβCD) complexed solid lipid nanoparticles (SLNs) of IR were prepared, optimized, and characterized. The current study aimed to confirm the reproducibility of the previous methodology and to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of the selected lead formulations in an experimental animal model.

Methods: SLNs were prepared by hot homogenization followed by probe sonication with IR/HPβCD inclusion complex loaded into a solid lipid (Dynasan 112). SLNs were evaluated for physical characteristics, drug content, entrapment efficiency, in vitro release profile, and surface morphology. The pharmacokinetic and pharmacodynamic behavior of the SLNs were evaluated in Wistar rats.

Results: Photon correlation spectroscopy, drug content, entrapment efficiency, and dissolution studies results were reproducible and consistent with our earlier investigation. PK studies showed 2.1-, 6.6-, and 9.9-fold improvement in the relative oral bioavailability of the drug from IR-HPβCD, IR-SLN, and IR-HPβCD-SLN formulations, respectively compared to IR suspension. However, IR-HPβCD-SLNs showed 1.5- and 4.7-fold improvement in the relative oral bioavailability of the drug compared to IR-SLN and IR-HPβCD formulations, respectively. PD studies in hypertensive Wistar rats showed a good control over systolic blood pressure for 48 h for SLN formulations compared to 2 h for IR suspension. However, the IR-HPβCD inclusion complex exhibited immediate antihypertensive activity (0.5 h) with a period of systolic blood pressure control similar to IR suspension.

Conclusions: The current approach exhibited improved oral bioavailability along with improved and prolonged pharmacodynamic effect.

Keywords: Irbesartan, Cyclodextrin, SLNs, Pharmacokinetic, Pharmacodynamic.


Citation styles

APA
Dudhipala, N., Ettireddy, S., Youssef, A.A.A., Puchchakayala, G. (2023). Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics, 7(1), 117-127. https://doi.org/10.7150/ntno.78102.

ACS
Dudhipala, N.; Ettireddy, S.; Youssef, A.A.A.; Puchchakayala, G. Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics 2023, 7 (1), 117-127. DOI: 10.7150/ntno.78102.

NLM
Dudhipala N, Ettireddy S, Youssef AAA, Puchchakayala G. Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics 2023; 7(1):117-127. doi:10.7150/ntno.78102. https://www.ntno.org/v07p0117.htm

CSE
Dudhipala N, Ettireddy S, Youssef AAA, Puchchakayala G. 2023. Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics. 7(1):117-127.

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