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

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 ± 1.7nm, 83.51 ± 2.15%, and 83.3 ± 3.86% after 24h, 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.