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  • Title: Zinc-alginate microparticles for controlled pulmonary delivery of proteins prepared by spray-drying.
    Author: Möbus K, Siepmann J, Bodmeier R.
    Journal: Eur J Pharm Biopharm; 2012 May; 81(1):121-30. PubMed ID: 22342605.
    Abstract:
    The aim of this study was to prepare novel Zn(2+)-cross-linked alginate microparticles for controlled pulmonary delivery of protein drugs via a simple one-step spray-drying process and to physicochemically characterize these systems. Microparticles were prepared by spray-drying aqueous alginate solutions, containing the model protein BSA, Zn(NH(3))(4)SO(4), and optionally additional excipients. Upon ammonia evaporation, the alginate was cross-linked by Zn(2+)-ions. The microparticles were characterized by SEM, laser and X-ray diffraction, gel electrophoresis, aerodynamic particle size, and drug release measurements. Particles in a size range suitable for deep lung administration were obtained. Pure alginate microparticles were spherical in shape, whereas the addition of zinc led to a more collapsed geometry. Protein release depended on the (i) alginate:ZnSO(4) ratio (minimum release rate at 2:1); (ii) BSA content (decreasing release rate and extent with decreasing BSA content); (iii) type of release medium (increasing release rate with increasing phosphate concentration). The emitted microparticle dose was high for all formulations (∼90%). Fine particle fractions (FPF, depositing in the deep lung) up to 40% could be achieved. The FPF was affected by the BSA content, alginate:ZnSO(4) ratio and presence/absence of poloxamer. Thus, novel Zn(2+)-cross-linked alginate microparticles were prepared via a simple one-step process, providing an interesting potential for controlled pulmonary delivery of proteins.
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