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Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy

Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy
Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy
Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1-5 microm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p < 0.05) reduce the elasticity and yield stress of CF sputum. The superior physical properties of UFH/L-leucine indicate this is the preferred formulation for development as an inhaled mucolytic.
0022-3549
4857-4868
Shur, Jagdeep
adb5d528-2977-4e62-a91c-7c29f2529e6b
Nevell, Thomas G.
5d09d976-ee18-49da-8150-09a4b4d2de2a
Ewen, Richard J.
2d88deb9-ce0c-4558-b3f1-07fa843388b3
Price, Robert
e2f4942a-e750-41bb-a222-3af767249dad
Smith, Andrew
28d2a985-1801-4e42-9a43-8061526d8e48
Barbu, Eugen
7d06b2c4-bdf8-41b2-8a77-f0717e00d147
Conway, Joy H.
bbe9a2e4-fb85-4d4a-a38c-0c1832c32d06
Carroll, Mary P.
f7e407a5-f7fa-4efd-a7f1-8e6140b86f50
Shute, Janis K.
a5eef853-50ae-4abf-9e34-1c873601437f
Smith, James R.
251bbbe5-0022-4475-979c-894f608eac60
Shur, Jagdeep
adb5d528-2977-4e62-a91c-7c29f2529e6b
Nevell, Thomas G.
5d09d976-ee18-49da-8150-09a4b4d2de2a
Ewen, Richard J.
2d88deb9-ce0c-4558-b3f1-07fa843388b3
Price, Robert
e2f4942a-e750-41bb-a222-3af767249dad
Smith, Andrew
28d2a985-1801-4e42-9a43-8061526d8e48
Barbu, Eugen
7d06b2c4-bdf8-41b2-8a77-f0717e00d147
Conway, Joy H.
bbe9a2e4-fb85-4d4a-a38c-0c1832c32d06
Carroll, Mary P.
f7e407a5-f7fa-4efd-a7f1-8e6140b86f50
Shute, Janis K.
a5eef853-50ae-4abf-9e34-1c873601437f
Smith, James R.
251bbbe5-0022-4475-979c-894f608eac60

Shur, Jagdeep, Nevell, Thomas G., Ewen, Richard J., Price, Robert, Smith, Andrew, Barbu, Eugen, Conway, Joy H., Carroll, Mary P., Shute, Janis K. and Smith, James R. (2008) Cospray-dried unfractionated heparin with L-leucine as a dry powder inhaler mucolytic for cystic fibrosis therapy. Journal of Pharmaceutical Sciences, 97 (11), 4857-4868. (doi:10.1002/jps.21362). (PMID:18351636)

Record type: Article

Abstract

Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1-5 microm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p < 0.05) reduce the elasticity and yield stress of CF sputum. The superior physical properties of UFH/L-leucine indicate this is the preferred formulation for development as an inhaled mucolytic.

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Published date: November 2008
Organisations: Health Sciences

Identifiers

Local EPrints ID: 72481
URI: https://eprints.soton.ac.uk/id/eprint/72481
ISSN: 0022-3549
PURE UUID: f7e45098-ce47-44c0-bba8-3fb0f5c2e70c
ORCID for Joy H. Conway: ORCID iD orcid.org/0000-0001-6464-1526

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Date deposited: 16 Feb 2010
Last modified: 19 Jul 2019 23:43

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Contributors

Author: Jagdeep Shur
Author: Thomas G. Nevell
Author: Richard J. Ewen
Author: Robert Price
Author: Andrew Smith
Author: Eugen Barbu
Author: Joy H. Conway ORCID iD
Author: Mary P. Carroll
Author: Janis K. Shute
Author: James R. Smith

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