Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity

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Apomorphine and its esters : Differences in Caco-2 cell permeability and chylomicron affinity. / Borkar, Nrupa; Chen, Zhizhong; Saaby, Lasse; Müllertz, Anette; Håkansson, Anders E; Schönbeck, Christian; Yang, Mingshi; Holm, René; Mu, Huiling.

In: International Journal of Pharmaceutics, Vol. 509, No. 1-2, 06.06.2016, p. 499–506.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Borkar, N, Chen, Z, Saaby, L, Müllertz, A, Håkansson, AE, Schönbeck, C, Yang, M, Holm, R & Mu, H 2016, 'Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity', International Journal of Pharmaceutics, vol. 509, no. 1-2, pp. 499–506. https://doi.org/10.1016/j.ijpharm.2016.06.010

APA

Borkar, N., Chen, Z., Saaby, L., Müllertz, A., Håkansson, A. E., Schönbeck, C., ... Mu, H. (2016). Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity. International Journal of Pharmaceutics, 509(1-2), 499–506. https://doi.org/10.1016/j.ijpharm.2016.06.010

Vancouver

Borkar N, Chen Z, Saaby L, Müllertz A, Håkansson AE, Schönbeck C et al. Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity. International Journal of Pharmaceutics. 2016 Jun 6;509(1-2):499–506. https://doi.org/10.1016/j.ijpharm.2016.06.010

Author

Borkar, Nrupa ; Chen, Zhizhong ; Saaby, Lasse ; Müllertz, Anette ; Håkansson, Anders E ; Schönbeck, Christian ; Yang, Mingshi ; Holm, René ; Mu, Huiling. / Apomorphine and its esters : Differences in Caco-2 cell permeability and chylomicron affinity. In: International Journal of Pharmaceutics. 2016 ; Vol. 509, No. 1-2. pp. 499–506.

Bibtex

@article{656c6bc203fc4e708b9d02029cf53c31,
title = "Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity",
abstract = "Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine, monolauroyl apomorphine (MLA) and dilauroyl apomorphine (DLA) were subjected to apical to basolateral (A-B) and basolateral to apical (B-A) transport across Caco-2 cell monolayer. The stability of these compounds was also assessed by incubation at intestinal pH and physiological pH with and without Caco-2 cells. Molecular dynamics (MD) simulations were performed to understand the stability of the esters on a molecular level. The affinity of the compounds towards plasma derived chylomicrons was assessed. The A-B transport of intact DLA was about 150 times lower than the transport of apomorphine. In contrast, MLA was highly unstable in the aqueous media leading to apomorphine appearance basolaterally. MD simulations possibly explained the differences in hydrolysis susceptibilities of DLA and MLA. The affinity of apomorphine diesters towards plasma derived chylomicrons provided an understanding of their potential lymphatic transport. Even though, the intact DLA transport is not favorable; the conversion of DLA to MLA is therefore, an important step for intestinal apomorphine absorption.",
author = "Nrupa Borkar and Zhizhong Chen and Lasse Saaby and Anette M{\"u}llertz and H{\aa}kansson, {Anders E} and Christian Sch{\"o}nbeck and Mingshi Yang and Ren{\'e} Holm and Huiling Mu",
note = "Copyright {\circledC} 2016. Published by Elsevier B.V.",
year = "2016",
month = "6",
day = "6",
doi = "10.1016/j.ijpharm.2016.06.010",
language = "English",
volume = "509",
pages = "499–506",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

RIS

TY - JOUR

T1 - Apomorphine and its esters

T2 - Differences in Caco-2 cell permeability and chylomicron affinity

AU - Borkar, Nrupa

AU - Chen, Zhizhong

AU - Saaby, Lasse

AU - Müllertz, Anette

AU - Håkansson, Anders E

AU - Schönbeck, Christian

AU - Yang, Mingshi

AU - Holm, René

AU - Mu, Huiling

N1 - Copyright © 2016. Published by Elsevier B.V.

PY - 2016/6/6

Y1 - 2016/6/6

N2 - Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine, monolauroyl apomorphine (MLA) and dilauroyl apomorphine (DLA) were subjected to apical to basolateral (A-B) and basolateral to apical (B-A) transport across Caco-2 cell monolayer. The stability of these compounds was also assessed by incubation at intestinal pH and physiological pH with and without Caco-2 cells. Molecular dynamics (MD) simulations were performed to understand the stability of the esters on a molecular level. The affinity of the compounds towards plasma derived chylomicrons was assessed. The A-B transport of intact DLA was about 150 times lower than the transport of apomorphine. In contrast, MLA was highly unstable in the aqueous media leading to apomorphine appearance basolaterally. MD simulations possibly explained the differences in hydrolysis susceptibilities of DLA and MLA. The affinity of apomorphine diesters towards plasma derived chylomicrons provided an understanding of their potential lymphatic transport. Even though, the intact DLA transport is not favorable; the conversion of DLA to MLA is therefore, an important step for intestinal apomorphine absorption.

AB - Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine, monolauroyl apomorphine (MLA) and dilauroyl apomorphine (DLA) were subjected to apical to basolateral (A-B) and basolateral to apical (B-A) transport across Caco-2 cell monolayer. The stability of these compounds was also assessed by incubation at intestinal pH and physiological pH with and without Caco-2 cells. Molecular dynamics (MD) simulations were performed to understand the stability of the esters on a molecular level. The affinity of the compounds towards plasma derived chylomicrons was assessed. The A-B transport of intact DLA was about 150 times lower than the transport of apomorphine. In contrast, MLA was highly unstable in the aqueous media leading to apomorphine appearance basolaterally. MD simulations possibly explained the differences in hydrolysis susceptibilities of DLA and MLA. The affinity of apomorphine diesters towards plasma derived chylomicrons provided an understanding of their potential lymphatic transport. Even though, the intact DLA transport is not favorable; the conversion of DLA to MLA is therefore, an important step for intestinal apomorphine absorption.

U2 - 10.1016/j.ijpharm.2016.06.010

DO - 10.1016/j.ijpharm.2016.06.010

M3 - Journal article

C2 - 27282537

VL - 509

SP - 499

EP - 506

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -

ID: 162493135