Exploring the interactions of irbesartan-2-hydroxypropyl-β-cyclodextrin complex in micelles

Irbesartan is a beneficial drug against hypertension and other diseases. Although it is a polydynamic drug, it suffers from high lipophilicity. New formulations of the drug may increase its efficient pharmacological profile. Towards this aim, we have studied the interactions of irbesartan in simple or complexed form with 2- hydroxypropyl-cyclodextrin in micelles. The interactions of the drug in the two forms in the micelle environment are discussed. Of special interest, is the highly flexibility of the spacer phenyl rin

Host-Guest Interactions between Candesartan and Its Prodrug Candesartan Cilexetil in Complex with 2-Hydroxypropyl-β-cyclodextrin: On the Biological Potency for Angiotensin II Antagonism

Renin−angiotensin aldosterone system inhibitors are for 25 a long time extensively used for the treatment of cardiovascular and renal 26 diseases. AT1 receptor blockers (ARBs or sartans) act as antihypertensive 27 drugs by blocking the octapeptide hormone Angiotensin II to stimulate 28 AT1 receptors. The antihypertensive drug candesartan (CAN) is the active 29 metabolite of candesartan cilexetil (Atacand, CC). Complexes of 30 candesartan and candesartan cilexetil with 2-hydroxylpropyl-β-cyclodextrin 31 (2-HP-β-CD) were characterized using high-resolution electrospray 32 ionization mass spectrometry and solid state 13C cross-polarization/ 33 magic angle spinning nuclear magnetic resonance (CP/MAS NMR) 34 spectroscopy. The 13C CP/MAS results showed broad peaks especially in 35 the aromatic region, thus confirming the strong interactions between 36 cyclodextrin and drugs. This experimental evidence was in accordance with molecular dynamics simulations and quantum mechanical calculations. The 37 synthesized and characterized complexes were evaluated biologically in vitro. It was shown that as a result of CAN’s complexation, CAN exerts higher 38 antagonistic activity than CC. Therefore, a formulation of CC with 2-HP-β-CD is not indicated, while the formulation with CAN is promising and needs 39 further investigation. This intriguing result is justified by the binding free energy calculations, which predicted efficient CC binding to 2-HP-β-CD, and 40 thus, the molecule’s availability for release and action on the target is diminished. In contrast, CAN binding was not favored, and this may allow easy 41 release for the drug to exert its bioactivity