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Nanostructured lipid carriers of isradipine for effective management of hypertension and isoproterenol induced myocardial infarction

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Abstract 

The objective of the present paper is to formulate nanostructured lipid carriers (NLCs) of a calcium channel blocker, isradipine, to enhance its oral bioavailability and prolong its antihypertensive effect apart from evaluating efficacy of the formulation in isoproterenol induced myocardial infarction in rats. Formulation was optimized using quality by design (QbD)–based approach. Three factors i.e., total lipid concentration (%), homogenization pressure (bar), and number of cycles were optimized through Box-Behnken design to estimate their effect on critical quality attributes (CQAs) viz., size (nm), % entrapment efficiency, and in vitro % drug release which were found to be 80.9 ± 1.7 nm, 83.51 ± 2.15%, and 83.3 ± 3.86% after 24 h, respectively. In vivo pharmacokinetic study indicated 4.207 and 1.907 times increase in the oral bioavailability of optimized nanostructured lipid carrier without and with cycloheximide (lymphatic transport inhibitor), respectively. Treatment with ISO (isoproterenol) significantly diverges the levels of antioxidant marker, TBARS (thiobarbituric acid), and ultrastructure of the cardiac tissue indicating significant myocardial damage. Pretreatment of nanostructured lipid carrier of isradipine (ISD-NLCs) significantly prevented the antioxidant status and ultrastructural changes in the heart. In conclusion, this study confirms that optimized NLCs can substantially improve oral bioavailability of isradipine and presents a promising strategy in the management of hypertension for longer duration of time apart from demonstrating its preclinical efficacy in cardioprotection.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This project was financially assisted by the Hamdard National Foundation (HNF), New Delhi.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Tausif Alam, Sanjula Baboota & Javed Ali

  2. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Mohd Asif Ansari

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  1. Tausif Alam
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Contributions

Conceptualization: Tausif Alam; methodology: Tausif Alam, Mohd Asif Ansari; formal analysis and investigation: Tausif Alam; writing—original draft preparation: Tausif Alam; writing—review and editing: Javed Ali, Sanjula Baboota; funding acquisition: Hamdard; resources: Javed Ali; supervision: Javed Ali, Sanjula Baboota.

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Correspondence to Javed Ali.

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I, Dr. Javed Ali, corresponding author of this research article on behalf of all the authors (Mr. Tausif Alam, Mr. Asif Ansari, Dr. Sanjula Baboota) hereby confirm that this article is original, does not infringe on any copyright, is not under consideration by any other journal, and has not been previously published. Ethical approval for conducting experiment on animals has been sought and obtained as necessary.

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Alam, T., Ansari, M.A., Baboota, S. et al. Nanostructured lipid carriers of isradipine for effective management of hypertension and isoproterenol induced myocardial infarction. Drug Deliv. and Transl. Res. 12, 577–588 (2022). https://doi.org/10.1007/s13346-021-00958-x

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  • DOI: https://doi.org/10.1007/s13346-021-00958-x

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