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Antihypertensive activity and molecular interactions of irbesartan in complex with 2‐hydroxypropyl‐β‐cyclodextrin
Author(s) -
Leonis Georgios,
Christodoulou Eirini,
Ntountaniotis Dimitrios,
Chatziathanasiadou Maria V.,
Mavromoustakos Thomas,
Naziris Nikolaos,
Chountoulesi Maria,
Demetzos Costas,
Valsami Georgia,
Damalas Dimitrios E.,
Tzakos Andreas G.,
Thomaidis Nikolaos S.,
Karageorgos Vlasios,
Liapakis Georgios
Publication year - 2020
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13664
Subject(s) - irbesartan , lipophilicity , chemistry , pharmacology , cyclodextrin , dissolution , complex formation , drug , combinatorial chemistry , medicine , stereochemistry , chromatography , organic chemistry , blood pressure , inorganic chemistry
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‐hydroxypropyl‐β‐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.