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Development of a platform for nasal delivery of peptides and vaccines using powder carriers based on starch/poly(acrylic) acid

Delphine Coucke UGent (2009)
abstract
The interest in and importance of systemic drug delivery via the nasal route have expanded in recent decades since nasal administration offers an interesting alternative for the conventional oral and parenteral drug delivery routes. In this thesis, the nasal route was selected as an alternative route for peptide and vaccine delivery. A spray-dried combination of maize starch (Amioca®) and a cross-linked acrylic acid-based polymer (Carbopol® 974P) was used as powder carrier to amplify the mucoadhesive capacity of the formulation. In a first part of the study, the Amioca®/Carbopol® powder formulation was subjected to a heat treatment procedure. After heat treatment the water-absorbing capacity, viscosity and elasticity of the muco-adhesive powder increased. NMR analysis in combination with FT-IR indicated that heat treatment induced a low degree of cross-linking between the polymers. Nasal administration of Amioca®/Carbopol® 974P powders without heat treatment resulted in an absolute bioavailability in rabbits of 8.2 ± 3.0 % for insulin. Due to the difference in water-absorbing capacity (which opened the tight junctions of the nasal mucosa), elasticity and plasticity (which reduced mucociliairy clearance and prolonged residence time) heat treatment at 120°C improved the bioavailability: 36.5 ± 11.0 after heat treatment during 1h. In a second part of the study, the Amioca®/Carbopol® mixture was co-spray-dried with metoprolol tartrate (used as model molecule) in order to develop a powder suitable for nasal drug delivery via a one-step manufacturing process. The bioavailability of metoprolol tartrate after nasal administration of this powder to rabbits was compared with powders manufactured via other procedures. The study showed that co-processing of a mucoadhesive Amioca®/Carbopol® 974P formulation with metoprolol tartrate via co-spray-drying did not provide an added value towards the bioavailability of the drug after nasal administration of the mucoadhesive powder. In a third part of the study, the Amioca®/Carbopol® powder formulations spray-dried in different ratios (ratio: 0/100; 25/75; 50/50; 85/15; 100/0, w/w) were used as carriers of a viral antigen. A comparison of these formulations for intranasal delivery of heat-inactivated influenza virus combined with LTR192G adjuvant was made in vivo in a rabbit model. Individual rabbit sera were tested for seroconversion against hemagglutinin (HA), the major surface antigen of influenza. It was demonstrated that the use of bioadhesive carriers based on Amioca® starch and poly(acrylic acid) facilitates the induction of a systemic anti-HA antibody response after intranasal vaccination with a whole virus influenza vaccine.
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
year
type
dissertation (monograph)
subject
keyword
Powder formulation, Muco-adhesion, Nasal delivery, Nasal vaccination
pages
VII, 171 pages
publisher
Ghent University, Faculty of Pharmaceutical Sciences
place of publication
Ghent, Belgium
defense location
Gent : Faculteit Farmaceutische Wetenschappen (Auditorium I, Harelbekestraat 72)
defense date
2009-06-22 18:00
language
English
UGent publication?
yes
classification
D1
copyright statement
I have retained and own the full copyright for this publication
id
715342
handle
http://hdl.handle.net/1854/LU-715342
alternative location
http://lib.ugent.be/fulltxt/RUG01/001/344/719/RUG01-001344719_2010_0001_AC.pdf
date created
2009-07-08 10:09:01
date last changed
2009-07-14 10:21:30
@phdthesis{715342,
  abstract     = {The interest in and importance of systemic drug delivery via the nasal route have expanded in recent decades since nasal administration offers an interesting alternative for the conventional oral and parenteral drug delivery routes. In this thesis, the nasal route was selected as an alternative route for peptide and vaccine delivery. 
A spray-dried combination of maize starch (Amioca{\textregistered}) and a cross-linked acrylic acid-based polymer (Carbopol{\textregistered} 974P) was used as powder carrier to amplify the mucoadhesive capacity of the formulation. 
In a first part of the study, the Amioca{\textregistered}/Carbopol{\textregistered} powder formulation was subjected to a heat treatment procedure. After heat treatment the water-absorbing capacity, viscosity and elasticity of the muco-adhesive powder increased. NMR analysis in combination with FT-IR indicated that heat treatment induced a low degree of cross-linking between the polymers. Nasal administration of Amioca{\textregistered}/Carbopol{\textregistered} 974P powders without heat treatment resulted in an absolute bioavailability in rabbits of 8.2 {\textpm} 3.0 \% for insulin. Due to the difference in water-absorbing capacity (which opened the tight junctions of the nasal mucosa), elasticity and plasticity (which reduced mucociliairy clearance and prolonged residence time) heat treatment at 120{\textdegree}C improved the bioavailability: 36.5 {\textpm} 11.0 after heat treatment during 1h. 
In a second part of the study, the Amioca{\textregistered}/Carbopol{\textregistered} mixture was co-spray-dried with metoprolol tartrate (used as model molecule) in order to develop a powder suitable for nasal drug delivery via a one-step manufacturing process. The bioavailability of metoprolol tartrate after nasal administration of this powder to rabbits was compared with powders manufactured via other procedures. The study showed that co-processing of a mucoadhesive Amioca{\textregistered}/Carbopol{\textregistered} 974P formulation with metoprolol tartrate via co-spray-drying did not provide an added value towards the bioavailability of the drug after nasal administration of the mucoadhesive powder.
In a third part of the study, the Amioca{\textregistered}/Carbopol{\textregistered} powder formulations spray-dried in different ratios (ratio: 0/100; 25/75; 50/50; 85/15; 100/0, w/w) were used as carriers of a viral antigen. A comparison of these formulations for intranasal delivery of heat-inactivated influenza virus combined with LTR192G adjuvant was made in vivo in a rabbit model. Individual rabbit sera were tested for seroconversion against hemagglutinin (HA), the major surface antigen of influenza. It was demonstrated that the use of bioadhesive carriers based on Amioca{\textregistered} starch and poly(acrylic acid) facilitates the induction of a systemic anti-HA antibody response after intranasal vaccination with a whole virus influenza vaccine.},
  author       = {Coucke, Delphine},
  keyword      = {Powder formulation,Muco-adhesion,Nasal delivery,Nasal vaccination},
  language     = {eng},
  pages        = {VII, 171},
  publisher    = {Ghent University, Faculty of Pharmaceutical Sciences},
  school       = {Ghent University},
  title        = {Development of a platform for nasal delivery of peptides and vaccines using powder carriers based on starch/poly(acrylic) acid},
  url          = {http://lib.ugent.be/fulltxt/RUG01/001/344/719/RUG01-001344719\_2010\_0001\_AC.pdf},
  year         = {2009},
}

Chicago
Coucke, Delphine. 2009. “Development of a Platform for Nasal Delivery of Peptides and Vaccines Using Powder Carriers Based on Starch/poly(acrylic) Acid”. Ghent, Belgium: Ghent University, Faculty of Pharmaceutical Sciences.
APA
Coucke, D. (2009). Development of a platform for nasal delivery of peptides and vaccines using powder carriers based on starch/poly(acrylic) acid. Ghent University, Faculty of Pharmaceutical Sciences, Ghent, Belgium.
Vancouver
1.
Coucke D. Development of a platform for nasal delivery of peptides and vaccines using powder carriers based on starch/poly(acrylic) acid. [Ghent, Belgium]: Ghent University, Faculty of Pharmaceutical Sciences; 2009.
MLA
Coucke, Delphine. “Development of a Platform for Nasal Delivery of Peptides and Vaccines Using Powder Carriers Based on Starch/poly(acrylic) Acid.” 2009 : n. pag. Print.