Partition of Amphiphilic Molecules to Lipid Bilayers by ITC: Low-Affinity Solutes

Samelo, Jaime; Mora, María Julia; Granero, Gladys E.; Moreno, Maria João

doi:10.1021/acsomega.7b01145

Cited by 13 publications

(22 citation statements)

References 35 publications

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“…The latter is reported by an encapsulated pH-sensitive fluorescent probe. In spite of the high potential of this approach, the permeability coefficients obtained are not always consistent with those from other approaches [ 7 , 8 , 15 , 16 , 17 ]. Moreover, its validity has been questioned, mostly regarding the possible contribution of the rate of acid-base equilibria [ 18 , 19 ], although it was concluded by the same authors that this could not be the rate-limiting step [ 18 ].…”

Section: Introductioncontrasting

confidence: 67%

Calculation of Permeability Coefficients from Solute Equilibration Dynamics: An Assessment of Various Methods

2022

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Predicting the rate at which substances permeate membrane barriers in vivo is crucial for drug development. Permeability coefficients obtained from in vitro studies are valuable for this goal. These are normally determined by following the dynamics of solute equilibration between two membrane-separated compartments. However, the correct calculation of permeability coefficients from such data is not always straightforward. To address these problems, here we develop a kinetic model for solute permeation through lipid membrane barriers that includes the two membrane leaflets as compartments in a four-compartment model. Accounting for solute association with the membrane allows assessing various methods in a wide variety of conditions. The results showed that the often-used expression Papp= β × r/3 is inapplicable to very large or very small vesicles, to moderately or highly lipophilic solutes, or when the development of a significant pH gradient opposes the solute’s flux. We establish useful relationships that overcome these limitations and allow predicting permeability in compartmentalised in vitro or in vivo systems with specific properties. Finally, from the parameters for the interaction of the solute with the membrane barrier, we defined an intrinsic permeability coefficient that facilitates quantitative comparisons between solutes.

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Section: Introductioncontrasting

confidence: 67%

Calculation of Permeability Coefficients from Solute Equilibration Dynamics: An Assessment of Various Methods

2022

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“…x 10 5 ᴍ 1 which is lower than DOPC aloneand consistent with data reported for liposomes. 56 As Rif is zwitterionic at physiological pH (7.4) with 40% in the anionic form. The lower affinity of Rif for DOPC:DOPG:DOPE (representative of a bacterial membrane) maybe attributed in part to repulsion between the ionized Rif and negatively charged lipids.…”

Section: Discussionmentioning

confidence: 99%

Microcavity-Supported Lipid Bilayers; Evaluation of Drug–Lipid Membrane Interactions by Electrochemical Impedance and Fluorescence Correlation Spectroscopy

et al. 2019

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Many drugs have intracellular or membrane-associated targets thus understanding their interaction with the cell membrane is of value in drug development. Cell-free tools used to predict membrane interactions should replicate the molecular organization of the membrane. Microcavity array supported lipid bilayer (MSLB) platform are versatile biophysical models of the cell membrane that combine liposome-like membrane fluidity with stability and addressability. We used an MSLB herein to interrogate drugmembrane interactions across seven drugs from different classes, including non-steroidal antiinflammatories; Ibuprofen (Ibu) and Diclofenac (Dic), antibiotics; Rifampicin (Rif), Levofloxacin (Levo) and Pefloxacin (Pef), and bisphosphonates; Alendronate (Ale) and Clodronate (Clo). Fluorescence lifetime correlation spectroscopy (FLCS) and electrochemical impedance spectroscopy (EIS) were used to evaluate the impact of drug on DOPC and binary bilayers over physiologically relevant drug concentrations. Whereas FLCS data revealed Ibu, Levo, Pef, Ale and Clo had no impact on lipid lateral

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“…Levofloxacin [236][237][238], Clarithromycin [236], Isoniazid N -acylated derivatives [239], Rifampicin [234,240], Mangostin [241], Trimethoprim [242], Negamycin [243] Potential antibiotic Kanamycin A [133], nTZDpa and its derivatives [244], Cholic acid derived amphiphiles [245], γ-terpineol [246], Bithionol [247] Antimicrobial compound Chlorhexidine [248][249][250], Triclosan [251], Octenidine [250] Antiparasitic Praziquantel [252] Antiviral drugs Darunavir [253], Amantadine [254][255][256], Spiro[pyrrolidine-2,2 -adamantane] [254,255], 20,30-dideoxyadenosine (Didanosine) [242], Saffron [257] Antifungal drug Itraconazole, [184,186,187,258], Nystatin [259], Amphotericin B [260] Rheumatoid arthritis Lapatinib [213] Nonsteroidal antiinflammatory drugs, inhibitor of cyclooxygenase-1 and -2…”

Section: Application and Target Drugs And Pharmaceuticsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Partition of Amphiphilic Molecules to Lipid Bilayers by ITC: Low-Affinity Solutes

Cited by 13 publications

References 35 publications

Calculation of Permeability Coefficients from Solute Equilibration Dynamics: An Assessment of Various Methods

Calculation of Permeability Coefficients from Solute Equilibration Dynamics: An Assessment of Various Methods

Microcavity-Supported Lipid Bilayers; Evaluation of Drug–Lipid Membrane Interactions by Electrochemical Impedance and Fluorescence Correlation Spectroscopy

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

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