Evaluation of EGCG Loading Capacity in DMPC Membranes

Filipa Pires, Vananélia P. N. Geraldo, Bárbara Rodrigues, António de Granada-Flor, Rodrigo F. M. de Almeida, Osvaldo N. Oliveira, Bruno L. Victor, Miguel Machuqueiro, Maria Raposo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Catechins are molecules with potential use in different pathologies such as diabetes and cancer, but their pharmaceutical applications are often hindered by their instability in the bloodstream. This issue can be circumvented using liposomes as their nanocarriers for in vivo delivery. In this work, we studied the molecular details of (-)-epigallocatechin-3-gallate (EGCG) interacting with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer/bilayer systems to understand the catechin loading ability and liposome stability, using experimental and computational techniques. The molecular dynamics simulations show the EGCG molecules deep inside the lipid bilayer, positioned below the lipid ester groups, generating a concentration-dependent lipid condensation. This effect was also inferred from the surface pressure isotherms of DMPC monolayers. In the polarization-modulated infrared reflection absorption spectra assays, the predominant effect at higher concentrations of EGCG (e.g., 20 mol %) was an increase in lipid tail disorder. The steady-state fluorescence data confirmed this disordered state, indicating that the catechin-induced liposome aggregation outweighs the condensation effects. Therefore, by adding more than 10 mol % EGCG to the liposomes, a destabilization of the vesicles occurs with the ensuing release of entrapped catechins. The loading capacity for DMPC seems to be limited by its disordered lipid arrangements, typical of a fluid phase. To further increase the clinical usefulness of liposomes, lipid bilayers with more stable and organized assemblies should be employed to avoid aggregation at large concentrations of catechin.

Original languageEnglish
JournalLangmuir
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

gallates
Phosphorylcholine
Catechin
Liposomes
lipids
Lipids
membranes
Membranes
evaluation
Lipid bilayers
Condensation
Monolayers
Agglomeration
condensation
Molecules
Pathology
Medical problems
Drug products
infrared reflection
destabilization

Cite this

Pires, Filipa ; Geraldo, Vananélia P. N. ; Rodrigues, Bárbara ; Granada-Flor, António de ; Almeida, Rodrigo F. M. de ; Oliveira, Osvaldo N. ; Victor, Bruno L. ; Machuqueiro, Miguel ; Raposo, Maria. / Evaluation of EGCG Loading Capacity in DMPC Membranes. In: Langmuir. 2019.
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title = "Evaluation of EGCG Loading Capacity in DMPC Membranes",
abstract = "Catechins are molecules with potential use in different pathologies such as diabetes and cancer, but their pharmaceutical applications are often hindered by their instability in the bloodstream. This issue can be circumvented using liposomes as their nanocarriers for in vivo delivery. In this work, we studied the molecular details of (-)-epigallocatechin-3-gallate (EGCG) interacting with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer/bilayer systems to understand the catechin loading ability and liposome stability, using experimental and computational techniques. The molecular dynamics simulations show the EGCG molecules deep inside the lipid bilayer, positioned below the lipid ester groups, generating a concentration-dependent lipid condensation. This effect was also inferred from the surface pressure isotherms of DMPC monolayers. In the polarization-modulated infrared reflection absorption spectra assays, the predominant effect at higher concentrations of EGCG (e.g., 20 mol {\%}) was an increase in lipid tail disorder. The steady-state fluorescence data confirmed this disordered state, indicating that the catechin-induced liposome aggregation outweighs the condensation effects. Therefore, by adding more than 10 mol {\%} EGCG to the liposomes, a destabilization of the vesicles occurs with the ensuing release of entrapped catechins. The loading capacity for DMPC seems to be limited by its disordered lipid arrangements, typical of a fluid phase. To further increase the clinical usefulness of liposomes, lipid bilayers with more stable and organized assemblies should be employed to avoid aggregation at large concentrations of catechin.",
author = "Filipa Pires and Geraldo, {Vanan{\'e}lia P. N.} and B{\'a}rbara Rodrigues and Granada-Flor, {Ant{\'o}nio de} and Almeida, {Rodrigo F. M. de} and Oliveira, {Osvaldo N.} and Victor, {Bruno L.} and Miguel Machuqueiro and Maria Raposo",
note = "info:eu-repo/grantAgreement/FCT/5876/147412/PT# The authors acknowledge the financial support from FEDER, through Programa Operacional Factores de Competitividade COMPETE and Fundacio para a Ciencia e a Tecnologia through research project grants PEst-OE/FIS/UI0068/2011, UID/FIS/00068/2013, UID/FIS/00068/2019, UID/MULTI/00612/2019, UID/MULTI/04046/2019, PTDC/FIS-NAN/0909/2014, PTDC/QEQ:COM/5904/2014, and PTDC/BBB-BQB/6071/2014. The Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and Fundagao de Amparo a Pesquisa do Estado de Sao Paulo are also acknowledged. M.M. acknowledges fellowship SFRH/BPD/110491/2015 and contract CEECIND/02300/2017 grants, and F.P. acknowledges the fellowship grant PD/BD/106036/2015 from RABBIT Doctoral Programme (Portugal).",
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Evaluation of EGCG Loading Capacity in DMPC Membranes. / Pires, Filipa; Geraldo, Vananélia P. N.; Rodrigues, Bárbara; Granada-Flor, António de; Almeida, Rodrigo F. M. de; Oliveira, Osvaldo N.; Victor, Bruno L.; Machuqueiro, Miguel; Raposo, Maria.

In: Langmuir, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of EGCG Loading Capacity in DMPC Membranes

AU - Pires, Filipa

AU - Geraldo, Vananélia P. N.

AU - Rodrigues, Bárbara

AU - Granada-Flor, António de

AU - Almeida, Rodrigo F. M. de

AU - Oliveira, Osvaldo N.

AU - Victor, Bruno L.

AU - Machuqueiro, Miguel

AU - Raposo, Maria

N1 - info:eu-repo/grantAgreement/FCT/5876/147412/PT# The authors acknowledge the financial support from FEDER, through Programa Operacional Factores de Competitividade COMPETE and Fundacio para a Ciencia e a Tecnologia through research project grants PEst-OE/FIS/UI0068/2011, UID/FIS/00068/2013, UID/FIS/00068/2019, UID/MULTI/00612/2019, UID/MULTI/04046/2019, PTDC/FIS-NAN/0909/2014, PTDC/QEQ:COM/5904/2014, and PTDC/BBB-BQB/6071/2014. The Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and Fundagao de Amparo a Pesquisa do Estado de Sao Paulo are also acknowledged. M.M. acknowledges fellowship SFRH/BPD/110491/2015 and contract CEECIND/02300/2017 grants, and F.P. acknowledges the fellowship grant PD/BD/106036/2015 from RABBIT Doctoral Programme (Portugal).

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Catechins are molecules with potential use in different pathologies such as diabetes and cancer, but their pharmaceutical applications are often hindered by their instability in the bloodstream. This issue can be circumvented using liposomes as their nanocarriers for in vivo delivery. In this work, we studied the molecular details of (-)-epigallocatechin-3-gallate (EGCG) interacting with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer/bilayer systems to understand the catechin loading ability and liposome stability, using experimental and computational techniques. The molecular dynamics simulations show the EGCG molecules deep inside the lipid bilayer, positioned below the lipid ester groups, generating a concentration-dependent lipid condensation. This effect was also inferred from the surface pressure isotherms of DMPC monolayers. In the polarization-modulated infrared reflection absorption spectra assays, the predominant effect at higher concentrations of EGCG (e.g., 20 mol %) was an increase in lipid tail disorder. The steady-state fluorescence data confirmed this disordered state, indicating that the catechin-induced liposome aggregation outweighs the condensation effects. Therefore, by adding more than 10 mol % EGCG to the liposomes, a destabilization of the vesicles occurs with the ensuing release of entrapped catechins. The loading capacity for DMPC seems to be limited by its disordered lipid arrangements, typical of a fluid phase. To further increase the clinical usefulness of liposomes, lipid bilayers with more stable and organized assemblies should be employed to avoid aggregation at large concentrations of catechin.

AB - Catechins are molecules with potential use in different pathologies such as diabetes and cancer, but their pharmaceutical applications are often hindered by their instability in the bloodstream. This issue can be circumvented using liposomes as their nanocarriers for in vivo delivery. In this work, we studied the molecular details of (-)-epigallocatechin-3-gallate (EGCG) interacting with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) monolayer/bilayer systems to understand the catechin loading ability and liposome stability, using experimental and computational techniques. The molecular dynamics simulations show the EGCG molecules deep inside the lipid bilayer, positioned below the lipid ester groups, generating a concentration-dependent lipid condensation. This effect was also inferred from the surface pressure isotherms of DMPC monolayers. In the polarization-modulated infrared reflection absorption spectra assays, the predominant effect at higher concentrations of EGCG (e.g., 20 mol %) was an increase in lipid tail disorder. The steady-state fluorescence data confirmed this disordered state, indicating that the catechin-induced liposome aggregation outweighs the condensation effects. Therefore, by adding more than 10 mol % EGCG to the liposomes, a destabilization of the vesicles occurs with the ensuing release of entrapped catechins. The loading capacity for DMPC seems to be limited by its disordered lipid arrangements, typical of a fluid phase. To further increase the clinical usefulness of liposomes, lipid bilayers with more stable and organized assemblies should be employed to avoid aggregation at large concentrations of catechin.

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U2 - 10.1021/acs.langmuir.9b00372

DO - 10.1021/acs.langmuir.9b00372

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