Liposomes as biomembrane models: Biophysical techniques for drug-membrane interaction studies

Andrade, Stéphanie; Ramalho, Maria João; Loureiro, Joana A.; Pereira, Maria do Carmo

doi:10.1016/j.molliq.2021.116141

Cited by 43 publications

(35 citation statements)

References 111 publications

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“…The presence of cholesterol in the composition of the liposomal form of pirfenidone has the potential to increase the effectiveness of therapy. Thus, for the further development of effective pharmaceutical formulations of pirfenidone based on liposomes, it is necessary to comprehensively study the nature of its interaction with liposomes of various lipid compositions [17]. The inclusion of 10% cholesterol in the DPPC matrix is a classic approach to producing a liposomal drug formulation [18]; at such a concentration, it is possible to detect interesting effects of the influence of the composition of liposomes on the interaction with various ligands; however, the proportion of cholesterol is not yet so high as to dramatically change the properties of the bilayer.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

et al. 2022

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In this work, we studied the effect of as on the interaction of membrane DPPC with the key antifibrotic drug pirfenidone. Liposomal forms of pirfenidone were obtained using passive loading. The addition of cholesterol reduces the loading efficiency of pirfenidone by 10%. The main binding site of pirfenidone in DPPC liposomes is the carbonyl group: the interaction with PF significantly increases the proportion of low-hydrated carbonyl groups as revealed by ATR-FTIR spectroscopy. The phosphate group acts as an additional binding site; however, due to shielding by the choline group, this interaction is weak. The hydrophobic part of the bilayer is not involved in PF binding at room temperature. Cholesterol changes the way of interaction between carbonyl groups and pirfenidone probably because of the formation of two subpopulations of DPPC and causes a dramatic redistribution of carbonyl groups onto the degrees of hydration. The proportion of moderately hydrated carbonyl groups increases, apparently due to the deepening of pirfenidone into the circumpolar region of the bilayer. For the first time, a change in the microenvironment of pirfenidone upon binding to liposomes was shown: aromatic moiety interacts with the bilayer.

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Section: Introductionmentioning

confidence: 99%

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

et al. 2022

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“…Since biological membranes are very complex systems given the current understanding of lipid behavior, model membranes have been extensively used for study purposes instead of natural membranes. The most well-known biomimetic systems for such purposes are lipid monolayers, lipid vesicles, and supported lipid bilayers [ 47 ]. These models have been extensively studied using different biophysical techniques.…”

Section: Discussionmentioning

confidence: 99%

Infrared Spectroscopic Study of Multi-Component Lipid Systems: A Closer Approximation to Biological Membrane Fluidity

Klaiss-Luna

Manrique-Moreno

2022

Membranes

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Membranes are essential to cellular organisms, and play several roles in cellular protection as well as in the control and transport of nutrients. One of the most critical membrane properties is fluidity, which has been extensively studied, using mainly single component systems. In this study, we used Fourier transform infrared spectroscopy to evaluate the thermal behavior of multi-component supported lipid bilayers that mimic the membrane composition of tumoral and non-tumoral cell membranes, as well as microorganisms such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus. The results showed that, for tumoral and non-tumoral membrane models, the presence of cholesterol induced a loss of cooperativity of the transition. However, in the absence of cholesterol, the transitions of the multi-component lipid systems had sigmoidal curves where the gel and fluid phases are evident and where main transition temperatures were possible to determine. Additionally, the possibility of designing multi-component lipid systems showed the potential to obtain several microorganism models, including changes in the cardiolipin content associated with the resistance mechanism in Staphylococcus aureus. Finally, the potential use of multi-component lipid systems in the determination of the conformational change of the antimicrobial peptide LL-37 was studied. The results showed that LL-37 underwent a conformational change when interacting with Staphylococcus aureus models, instead of with the erythrocyte membrane model. The results showed the versatile applications of multi-component lipid systems studied by Fourier transform infrared spectroscopy.

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“…Liposomes are spherical vesicles composed of phospholipid bilayers enclosing aqueous compartments [2]. The amphiphilic property of phospholipids, which display hydrophilic polar heads and lipophilic tails, allows the encapsulation of hydrophilic compounds in the aqueous space and lipophilic compounds in the lipid bilayer [3].…”

Section: Introductionmentioning

confidence: 99%

Multi-Dose Intravenous Administration of Neutral and Cationic Liposomes in Mice: An Extensive Toxicity Study

et al. 2022

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Liposomes are widely used as delivery systems for therapeutic purposes. However, the toxicity associated with the multi-dose administration of these nanoparticles is not fully elucidated. Here, we evaluated the toxicity of the prolonged administration of liposomes composed of neutral or cationic phospholipids often used in drug and gene delivery. For that purpose, adult wild-type mice (C57Bl6) were randomly distributed into three groups receiving either vehicle (PBS), neutral, or cationic liposomes and subjected to repeated intravenous injections for a total of 10 doses administered over 3 weeks. Several parameters, including mortality, body weight, and glucose levels, were monitored throughout the trial. While these variables did not change in the group treated with neutral liposomes, the group treated with the positively charged liposomes displayed a mortality rate of 45% after 10 doses of administration. Additional urinalysis, blood tests, and behavioral assays to evaluate impairments of motor functions or lesions in major organs were also performed. The cationic group showed less forelimb peak force than the control group, alterations at the hematological level, and inflammatory components, unlike the neutral group. Overall, the results demonstrate that cationic liposomes are toxic for multi-dose administration, while the neutral liposomes did not induce changes associated with toxicity. Therefore, our results support the use of the well-known neutral liposomes as safe drug shuttles, even when repetitive administrations are needed.

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Liposomes as biomembrane models: Biophysical techniques for drug-membrane interaction studies

Cited by 43 publications

References 111 publications

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

Cholesterol Significantly Affects the Interactions between Pirfenidone and DPPC Liposomes: Spectroscopic Studies

Infrared Spectroscopic Study of Multi-Component Lipid Systems: A Closer Approximation to Biological Membrane Fluidity

Multi-Dose Intravenous Administration of Neutral and Cationic Liposomes in Mice: An Extensive Toxicity Study

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