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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.

A family of cationic Pluronic-based polyrotaxanes (PR(+)), threaded with 2-hydroxypropyl-β-cyclodextrin (HPCD), was synthesized for pDNA delivery into multiple cell lines. All PR(+) formed highly stable, positively charged pDNA complexes that were < 250 nm in diameter. The cellular uptake and pDNA transfection efficiencies of the PR(+):pDNA complexes was enhanced relative to the commercial transfection standards L2K and bPEI, while displaying similar or lower toxicity profiles. Charge density and threading efficiency of the PR(+) agent significantly influenced the colloidal stability and physical properties of the complexes, which impacted their intracellular transfection efficiencies. Taken together, our results suggest that HPCD: Pluronic PR(+) can be used as potent vectors for pDNA-based therapeutics.

Les constantes de stabilite pour l'inclusion de materiaux odorants avec 2-hydroxypropyl-β-cyclodextrine (2HP-β-CyD) dans une solution aqueuse ont ete determinees par la methode de tete libre statique. Les constantes de stabilite 1:1 obtenues par cette methode parviennent a un accord raisonnable avec les valeurs correspondantes dans la litterature. En outre, les profils de liberation des materiaux odorants a partir de la solution aqueuse 2HP-β-CyD ont ete etudies en faisant appel a la methode de tete libre dynamique. On a constate que la suppression de la liberation des materiaux odorants dependait de leurs constantes de stabilite.

Electrospray mass spectrometry has been used to study the complexation of ‘guest’ molecules with a mixture of hydroxypropyl-substituted β-cyclodextrin derivatives. In all cases studied, the predominant derivative was shown to contain a maximum of seven hydroxypropyl groups, most probably related to alkylation of each of the seven glucose units of the parent β-cyclodextrin. Chiral selectivity was not observed for D- and L-phenylalanine methyl esters. In contrast D-propranolol and L-tryptophan methyl ester formed stronger complexes than the corresponding L- and D-enantiomers, respectively. Molecular modelling studies were also carried out, in an attempt to identify the factors that can play a part in determining the mechanism of the observed non-covalent interactions.