Τίτλος:
Antihypertensive Activity and Molecular Interactions of Irbesartan in Complex with 2-Hydroxypropyl-β-Cyclodextrin
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
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
Περιοδικό:
Chemical Biology and Drug Design (formerly Journal of Peptide Research)
Λέξεις-κλειδιά:
2-hydroxypropyl-β-cyclodextrin, binding assays, differential scanning calorimetry, hypertension, irbesartan, mass spectrometry, molecular dynamics
Κύρια θεματική κατηγορία:
Θετικές Επιστήμες
