Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system

Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system
November 2004
Verena M. Leitner, a, Davide Guggi, a, Alexander H. Krauland, a and Andreas Bernkop-Schn?r, b
aInstitute of Pharmaceutical Technology and Biopharmaceutics, Centre of Pharmacy, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria
bDepartment of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef-Moeller-Haus, A-6020 Innsbruck, Austria
ournal of Controlled Release, Volume 100, Issue 1 , 5 November 2004, Pages 87-95
Science Direct
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Abstract
It was the aim of this study to develop and evaluate a nasal microparticulate delivery system for human growth hormone (hGH) based on the thiomer polycarbophil-cysteine (PCP-Cys) in combination with the permeation mediator glutathione (GSH). Microparticles were prepared by dissolving PCP-Cys/GSH/hGH (7.5:1:1.5), PCP/hGH (8.5:1.5), and mannitol/hGH (8.5:1.5) in demineralized water, followed by lyophilizationnext term and micronization. Particles were evaluated with regard to size distribution and swelling behavior using a laser diffraction particle size analyzer. The release of fluorescence-labelled hGH from microparticles was determined in Franz diffusion chambers. In vivo studies in rats were performed comparing the nasal bioavailability achieved by PCP-Cys/GSH/hGH microparticles with that of unmodified PCP/hGH microparticles and mannitol/hGH powder.
PCP-Cys/GSH/hGH and PCP/hGH microparticles showed a comparable size distribution (80% in the range of 4.8?23 ?m) and swelled to almost fourfold size in phosphate-buffered saline (PBS). Both formulations exhibited almost identical sustained drug release profiles. The intranasal administration of the PCP-Cys/GSH/hGH microparticulate formulation resulted in a relative bioavailability of 8.11?2.15%, which represents a 3-fold and 3.3-fold improvement compared to that of PCP/hGH microparticles and mannitol/hGH powder, respectively. The study suggests that the PCP-Cys/GSH/hGH nasal microparticulate formulation might represent a promising novel tool for the systemic delivery of hGH.