Enhanced Anti‐Bacterial Activity of Non‐Antibacterial Drug Candesartan Cilexetil by Delivery through Polymeric Micelles

Abstract

AbstractCandesartan Cilexetil (CC) is a prodrug of candesartan and an angiotensin II receptor antagonist. It is used as a drug for different diseases like myocardial infarction, hypertension, and heart failure. The applicability of CC is impeded due to its poor water solubility, low permeability, and low bioavailability. This study is targeted to improve the efficacy and bioavailability of CC by its delivery through MeO‐PEO5K‐PCL micelles. The effect of length of hydrophobic block (PCL) on size of the micelles, drug encapsulation efficiency, and drug release behavior is evaluated. MeO‐PEO5K‐PCL based micelles were prepared by solvent evaporation method. The size of PMs was determined by dynamic light scattering, morphology by atomic force microscopy, and critical micelles concentration by fluorescence method. Encapsulation efficiency and drug release behaviors of MeO‐PEO5K‐PCL based PMs were evaluated by UV‐visible spectroscopy and dispersion method, respectively. The size of micelles increased and drug release rate decreased with increase in the length of PCL block. Maximum encapsulation efficiency of 96.42 % for CC is achieved with ABCs having equal PEO and PCL block lengths. A comparison of antibacterial activity of CC in pure form and encapsulated in PMs against MRSA is conducted. The MIC50 for CC loaded PMs has decreased to more than half in comparison to pure drug. AFM based morphological analysis also confirmed the decrease in MIC50 by delivery through PMs.