Publication

Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections

Wahjudi, M., Murugappan, S., van Merkerk, R., Eissens, A. C., Visser, M. R., Hinrichs, W. L. J. & Quax, W. J., 12-Mar-2013, In : European Journal of Pharmaceutical Sciences. 48, 4-5, p. 637-643 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Wahjudi, M., Murugappan, S., van Merkerk, R., Eissens, A. C., Visser, M. R., Hinrichs, W. L. J., & Quax, W. J. (2013). Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections. European Journal of Pharmaceutical Sciences, 48(4-5), 637-643. https://doi.org/10.1016/j.ejps.2012.12.015

Author

Wahjudi, Mariana ; Murugappan, Senthil ; van Merkerk, Ronald ; Eissens, Anko C. ; Visser, Marinella R. ; Hinrichs, Wouter L. J. ; Quax, Wim J. / Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections. In: European Journal of Pharmaceutical Sciences. 2013 ; Vol. 48, No. 4-5. pp. 637-643.

Harvard

Wahjudi, M, Murugappan, S, van Merkerk, R, Eissens, AC, Visser, MR, Hinrichs, WLJ & Quax, WJ 2013, 'Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections', European Journal of Pharmaceutical Sciences, vol. 48, no. 4-5, pp. 637-643. https://doi.org/10.1016/j.ejps.2012.12.015

Standard

Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections. / Wahjudi, Mariana; Murugappan, Senthil; van Merkerk, Ronald; Eissens, Anko C.; Visser, Marinella R.; Hinrichs, Wouter L. J.; Quax, Wim J.

In: European Journal of Pharmaceutical Sciences, Vol. 48, No. 4-5, 12.03.2013, p. 637-643.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Wahjudi M, Murugappan S, van Merkerk R, Eissens AC, Visser MR, Hinrichs WLJ et al. Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections. European Journal of Pharmaceutical Sciences. 2013 Mar 12;48(4-5):637-643. https://doi.org/10.1016/j.ejps.2012.12.015


BibTeX

@article{e81eba747caa4e01a510ab05872878ac,
title = "Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections",
abstract = "In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20 degrees C and 55 degrees C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55 degrees C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of similar to 1.8 mu m implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation. (C) 2013 Elsevier B.V. All rights reserved.",
keywords = "Acyl-homoserine-lactone acylase, Spray-freeze-dried PvdQ, Mannitol, Trehalose, Inulin, CYSTIC-FIBROSIS PATIENTS, IGE MONOCLONAL-ANTIBODY, PROTEIN STABILITY, BIOFILM FORMATION, MANNITOL CRYSTALLIZATION, AEROSOL PERFORMANCE, BACTERIAL BIOFILMS, SIGNAL MOLECULES, QUORUM, INHIBITION",
author = "Mariana Wahjudi and Senthil Murugappan and {van Merkerk}, Ronald and Eissens, {Anko C.} and Visser, {Marinella R.} and Hinrichs, {Wouter L. J.} and Quax, {Wim J.}",
year = "2013",
month = "3",
day = "12",
doi = "10.1016/j.ejps.2012.12.015",
language = "English",
volume = "48",
pages = "637--643",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "ELSEVIER SCIENCE BV",
number = "4-5",

}

RIS

TY - JOUR

T1 - Development of a dry, stable and inhalable acyl-homoserine-lactone-acylase powder formulation for the treatment of pulmonary Pseudomonas aeruginosa infections

AU - Wahjudi, Mariana

AU - Murugappan, Senthil

AU - van Merkerk, Ronald

AU - Eissens, Anko C.

AU - Visser, Marinella R.

AU - Hinrichs, Wouter L. J.

AU - Quax, Wim J.

PY - 2013/3/12

Y1 - 2013/3/12

N2 - In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20 degrees C and 55 degrees C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55 degrees C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of similar to 1.8 mu m implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation. (C) 2013 Elsevier B.V. All rights reserved.

AB - In the lungs of cystic fibrosis (CF) patients, Pseudomonas aeruginosa commonly causes chronic infections. It has been shown that the P. aeruginosa quorum sensing (QS) system controls the expression of virulence factors during invasion and infection to host cells. PvdQ is an acyl-homoserine lactone (AHL) acylase able to degrade the signal molecule of P. aeruginosa QS. The role of PvdQ in inhibiting the QS and its successive virulence determinants has been established in in vitro as well as in in vivo, the latter in a Caenorabdhitis elegans model. For the treatment of pulmonary P. aeruginosa infections, we propose that PvdQ can be best administered directly to the lungs of the patients as a dry powder because this is expected to give specific advantages in delivery as compared to nebulizing. Therefore in this study we investigated the production of a PvdQ powder by spray-freeze drying using mannitol, trehalose and inulin as excipient. The activity of PvdQ in the powder was determined immediately after production and after subsequent storage during 4 weeks at 20 degrees C and 55 degrees C. We found that the enzymatic activity of PvdQ is fully maintained during spray-freeze drying using mannitol, trehalose or inulin as excipient. However, mannitol was not able to stabilize the protein during storage, while PvdQ incorporated in trehalose or inulin was fully stabilized even during storage at 55 degrees C for at least 4 weeks. The poor stabilizing capacities of mannitol during storage could be related to its crystalline nature while the excellent stabilizing capacities of trehalose and inulin during storage could be related to their amorphous nature. The trehalose and inulin-based particles consisted of porous spheres with a volume average aerodynamical diameter of similar to 1.8 mu m implying that they are suitable for pulmonary delivery. This is the first study in which an AHL-degrading enzyme is processed into spray-freeze-dried powder suitable for inhalation. (C) 2013 Elsevier B.V. All rights reserved.

KW - Acyl-homoserine-lactone acylase

KW - Spray-freeze-dried PvdQ

KW - Mannitol

KW - Trehalose

KW - Inulin

KW - CYSTIC-FIBROSIS PATIENTS

KW - IGE MONOCLONAL-ANTIBODY

KW - PROTEIN STABILITY

KW - BIOFILM FORMATION

KW - MANNITOL CRYSTALLIZATION

KW - AEROSOL PERFORMANCE

KW - BACTERIAL BIOFILMS

KW - SIGNAL MOLECULES

KW - QUORUM

KW - INHIBITION

U2 - 10.1016/j.ejps.2012.12.015

DO - 10.1016/j.ejps.2012.12.015

M3 - Article

VL - 48

SP - 637

EP - 643

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

IS - 4-5

ER -

ID: 5836638