190
while entropy may be favorable or not [28]. The van der Walls
interactions seem to play a significant role in the complexation [27,
28]. Regarding the affinity, in their majority the cyclodextrin-guest
interactions are weak (10–2000 M
−1
) [7], thus facilitating the
release of the guest molecule.
Herein, the study of HP-β-CD–losartan potassium inclusion
complex is investigated by ITC. The guest, losartan potassium, is a
known antihypertensive drug that blocks the angiotensin II receptor, though its efficacy as chemotherapeutic agent is, also, under
investigation with promising results [29–32]. Losartan potassium
displays high water solubility and low permeability and suffers from
low oral bioavailability (33%) [33]. Furthermore, it exhibits a short
half-life, approximately 2 h [33]. To overcome these disadvantages
many formulations have been conducted in order to improve its
pharmacokinetic profile [32, 34–36]. HP-β-CD is a hydroxypropyl
derivative of the natural cyclodextrin β-CD consisting of seven
d-glucopyranose units. HP-β-CD has been selected since the
attached hydroxypropyl groups offer high aqueous solubility compared to the lipophilic β-CD and make it non-toxic. Thus,
HP-β-CD is a widely applicable cyclodextrin as it has been used in
numerous formulations [15, 16, 18, 37].
In this work, the thermodynamics and the affinity of the inclusion of losartan potassium into the HP-β-CD are evaluated via
ITC. Through this experimental process, the experimental design,
the ITC practice, and the data interpretation are also discussed.
2 Materials
1. HP-β-CD (MW ≈ 1540 g/mol, 1.0 molar substitution dextrin)
(see Note 1).
2. Losartan potassium (MW = 461.007 g/mol).
3. PBS buffer (10 mM, pH = 7): Both interactants have to be dissolved in the same buffer (see Note 2).
4. Water (LC-MS grade) for the reference cell loading.
1. Degassing station to remove air bubbles from the samples.
2. Isothermal titration calorimeter.
3. Precision glass syringes for sample loading.
4. pH meter.
3 Methods
1. If the calorimeter software provides an application for experimental design and the binding constant of the studied complex2.1 Samples
2.2 Instrumentation
3.1 Experimental
Design
Maria V. Chatziathanasiadou et al.
while entropy may be favorable or not [28]. The van der Walls
interactions seem to play a significant role in the complexation [27,
28]. Regarding the affinity, in their majority the cyclodextrin-guest
interactions are weak (10–2000 M
−1
) [7], thus facilitating the
release of the guest molecule.
Herein, the study of HP-β-CD–losartan potassium inclusion
complex is investigated by ITC. The guest, losartan potassium, is a
known antihypertensive drug that blocks the angiotensin II receptor, though its efficacy as chemotherapeutic agent is, also, under
investigation with promising results [29–32]. Losartan potassium
displays high water solubility and low permeability and suffers from
low oral bioavailability (33%) [33]. Furthermore, it exhibits a short
half-life, approximately 2 h [33]. To overcome these disadvantages
many formulations have been conducted in order to improve its
pharmacokinetic profile [32, 34–36]. HP-β-CD is a hydroxypropyl
derivative of the natural cyclodextrin β-CD consisting of seven
d-glucopyranose units. HP-β-CD has been selected since the
attached hydroxypropyl groups offer high aqueous solubility compared to the lipophilic β-CD and make it non-toxic. Thus,
HP-β-CD is a widely applicable cyclodextrin as it has been used in
numerous formulations [15, 16, 18, 37].
In this work, the thermodynamics and the affinity of the inclusion of losartan potassium into the HP-β-CD are evaluated via
ITC. Through this experimental process, the experimental design,
the ITC practice, and the data interpretation are also discussed.
2 Materials
1. HP-β-CD (MW ≈ 1540 g/mol, 1.0 molar substitution dextrin)
(see Note 1).
2. Losartan potassium (MW = 461.007 g/mol).
3. PBS buffer (10 mM, pH = 7): Both interactants have to be dissolved in the same buffer (see Note 2).
4. Water (LC-MS grade) for the reference cell loading.
1. Degassing station to remove air bubbles from the samples.
2. Isothermal titration calorimeter.
3. Precision glass syringes for sample loading.
4. pH meter.
3 Methods
1. If the calorimeter software provides an application for experimental design and the binding constant of the studied complex2.1 Samples
2.2 Instrumentation
3.1 Experimental
Design
Maria V. Chatziathanasiadou et al.