Triptan partition in model membranes

Wood, Irene; Pickholz, Mónica

doi:10.1007/s00894-014-2463-6

Cited by 5 publications

(11 citation statements)

References 45 publications

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“…At this point, we analyzed drug orientations within the bilayer for each case. From the detailed analysis of the EDP of different NRT groups, we observed that, on average, most groups of pNRT overlapped within the bilayer, showing no preferential orientation [6]. However, we observed some particular behaviors for nNRT from both -W and -C conditions.…”

Section: Detailed Density Profilesmentioning

confidence: 75%

“…Both optimization and partial charge calculations used the polarized continuum model (PCM) [37] with a solvent dielectric constant of 80, corresponding to liquid water at room conditions. The PCM method needed to be consistent with our previous works [5,6,38]. The topologies and parameters for both nNRT and pNRT are supplied as additional material.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we focused our attention on the effects of protonated SMT and NRT on model membranes for drugs originally placed in aqueous phase [6]. In the present work, we extended our interest to study of the effects of ionization state and initial conditions on these interactions.…”

Section: Introductionmentioning

confidence: 98%

“…In a previous work, we studied the interaction of protonated triptans with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC) lipid bilayers by means of molecular dynamics (MD) simulations [5,6]. We found that SMT and NRT do not have access to the hydrophobic membrane region when first placed in water.…”

Section: Introductionmentioning

confidence: 99%

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Naratriptan aggregation in lipid bilayers: perspectives from molecular dynamics simulations

Wood

Pickholz

2016

J Mol Model

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In order to understand the interaction between naratriptan and a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline (POPC), we carried out molecular dynamics simulations. The simulations were performed considering neutral and protonated ionization states, starting from different initial conditions. At physiological pH, the protonated state of naratriptan is predominant. It is expected that neutral compounds could have larger membrane partition than charged compounds. However, for the specific case of triptans, it is difficult to study neutral species in membranes experimentally, making computer simulations an interesting tool. When the naratriptan molecules were originally placed in water, they partitioned between the bilayer/water interface and water phase, as has been described for similar compounds. From this condition, the drugs displayed low access to the hydrophobic environment, with no significant effects on bilayer organization. The molecules anchored in the interface, due mainly to the barrier function of the polar and oriented lipid heads. On the other hand, when placed inside the bilayer, both neutral and protonated naratriptan showed self-aggregation in the lipid tail environment. In particular, the protonated species exhibited a pore-like structure, dragging water through this environment. Graphical Abstract Different behaviour of Naratriptan and Sumatriptan, when the drugs were originally placed in the lipid core.

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Section: Detailed Density Profilesmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Naratriptan aggregation in lipid bilayers: perspectives from molecular dynamics simulations

Wood

Pickholz

2016

J Mol Model

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“…Within atomistic simulations it is possible to explore, for instance, the drug partition in the different bilayer regions and go deeper into the main interactions responsible for their localization [37]. The drug localization could be guided by specific interactions, such as hydrogen bond [36], cation-π (for aromatic molecules) [44], salt bridges [45,46], or entropic effects (hydrophobic drugs usually partitioned in the hydrophobic core [47].…”

Section: Atomistic Simulationsmentioning

confidence: 99%

Molecular Dynamics Simulations to Study Drug Delivery Systems

Albano¹,

Paula²,

Pickholz³

2018

Molecular Dynamics

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Molecular dynamics simulation is a very powerful tool to understand biomolecular processes. In this chapter, we go over different applications of this methodology to drug delivery systems (DDS) carried out in the group. DDS-a formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs-are an important component of drug development and therapeutics. Biocompatible nanoparticles are materials in the nanoscale that emerged as important players, improving efficacy of approved drugs, for example. The molecular understanding of the encapsulation process could be very helpful to guide the nanocarrier for a specific system. Here we discuss different applications of drug delivery carriers, such as liposomes, polymeric micelles, and polymersomes using atomistic and coarse grain (CG) molecular dynamics simulations.

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A sumatriptan coarse-grained model to explore different environments: interplay with experimental techniques

et al. 2018

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In this work, we developed a coarse-grained model of sumatriptan suitable for extensive molecular dynamics simulations. First, we confirmed the interfacial distribution of this drug in bilayers through cryogenic transmission electron microscopy and small-angle X-ray scattering techniques, as was predicted by our previous atomistic simulations. Based on these simulations, we developed a coarse-grained model for sumatriptan able to reproduce its overall molecular behavior, captured by atomistic simulations and experiments. We then tested the sumatriptan model in a micellar environment along with experimental characterization of sumatriptan-loaded micelles. The simulation results showed good agreement with photon correlation spectroscopy and electrophoretic mobility experiments performed in this work. The particle size of the obtained micelles was comparable with the simulated ones; meanwhile, zeta-potential results suggest adsorption of the drug on the micellar surface. This model is a step forward in the search for a suitable drug-delivery system for sumatriptan.

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Triptan partition in model membranes

Cited by 5 publications

References 45 publications

Naratriptan aggregation in lipid bilayers: perspectives from molecular dynamics simulations

Naratriptan aggregation in lipid bilayers: perspectives from molecular dynamics simulations

Molecular Dynamics Simulations to Study Drug Delivery Systems

A sumatriptan coarse-grained model to explore different environments: interplay with experimental techniques

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