TY - JOUR
TI - Antihypertensive Activity and Molecular Interactions of Irbesartan in Complex with 2-Hydroxypropyl-β-Cyclodextrin
AU - G. Leonis, E. Christodoulou, D. Ntountaniotis1, M. V. Chatziathanasiadou, T. Mavromoustakos, N. Naziris, M. Chountoulesi, C. Demetzos, G. Valsami, D. E. Damalas, A. G. Tzakos, N. S. Thomaidis, V. Karageorgos, G. Liapakis
JO - Chemical Biology and Drug Design (formerly Journal of Peptide Research)
PY - 2020
VL - 96
TODO - -
SP - 668-683
PB - Wiley
SN - 1747-0277, 1747-0285
TODO - 10.1111/cbdd.13664
TODO - 2-hydroxypropyl-β-cyclodextrin, binding assays, differential scanning calorimetry, hypertension,  irbesartan, mass spectrometry, molecular dynamics
TODO - Irbesartan (IRB) exerts beneficial effects either alone or in combination with other 
drugs on numerous diseases, such as cancer, diabetes, and hypertension. However, 
due to its high lipophilicity, IRB does not possess the optimum pharmacological efficiency. To circumvent this problem, a drug delivery system with 2-hydroxypropylβ-cyclodextrin (2-HP-β-CD) was explored. The 1:1 complex between IRB and 
2-HP-β-CD was identified through ESI QTF HRMS. Dissolution studies showed a 
higher dissolution rate of the lyophilized IRB–2-HP-β-CD complex than the tablet 
containing IRB at pH  =  1.2. DSC results revealed the differences of the thermal 
properties between the complex and various mixtures consisting of the two components, namely IRB and 2-HP-β-CD. Interestingly, depending on the way the mixture 
preparation was conducted, different association between the two components was 
observed. Molecular dynamics (MD) simulations predicted the favorable formation 
of the above complex and identified the dominant interactions between IRB and 
2-HP-β-CD. In vitro pharmacological results verified that the inclusion complex not 
only preserves the binding affinity of IRB for AT1R receptor, but also it slightly increases it. As the complex formulation lacks the problems of the tablet, our approach 
is a promising new way to improve the efficiency of IRB.
ER -