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

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.

Grantor dc:publisher

Ghent University, Faculty of Pharmaceutical Sciences

Year dc:date

2009

Author dc:creator

• Coucke, Delphine

Contributors dc:contributor

• Remon, Jean Paul
• Vervaet, Chris

• Medicine and Health Sciences
• Powder formulation
• Muco-adhesion
• Nasal delivery
• Nasal vaccination

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://biblio.ugent.be/publication/715342
https://biblio.ugent.be/publication/715342/file/4335013

OAI identifier oai:identifier

oai:archive.ugent.be:715342