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  • Title: Novel preparation techniques for alginate-poloxamer microparticles controlling protein release on mucosal surfaces.
    Author: Moebus K, Siepmann J, Bodmeier R.
    Journal: Eur J Pharm Sci; 2012 Feb 14; 45(3):358-66. PubMed ID: 22178531.
    Abstract:
    The objective of this study was to develop novel preparation techniques for protein-loaded, controlled release alginate-poloxamer microparticles with a size range suitable for pulmonary administration. Bovine serum albumin (BSA)-loaded microparticles were prepared by spray-drying aqueous polymer-drug solutions, followed by cross-linking the particles in aqueous or ethanolic CaCl(2) or aqueous ZnSO(4) solutions. The microparticles were characterized with respect to their morphology (optical and scanning electron microscopy), particle size (laser light diffraction), calcium content (atom absorption spectroscopy), alginate content (complexation with 1,9-dimethyl methylene blue) and in vitro drug release (modified Franz diffusion cell). The spray-dried microparticles were spherical in shape with a size range of 4-6μm. Aqueous cross-linking led to a significant size increase (10-15μm), whereas ethanolic cross-linking did not. The substantial drug loss (∼50%) during aqueous CaCl(2) cross-linking could be avoided by using aqueous ZnSO(4) or ethanolic CaCl(2) solutions. Protein release from microparticles cross-linked with ethanolic CaCl(2) solutions was much faster than in the case of aqueous CaCl(2) solutions, probably due to the lower calcium content. The salt concentration and temperature of the cross-linking solutions also affected the composition of and drug release from the microparticles. Cross-linked alginate-poloxamer microparticles can be produced in a size range appropriate for deep lung delivery and with controlled protein release kinetics (time frame: hours to days) with these novel preparation techniques. The systems offer an interesting potential for the controlled mucosal delivery of protein drugs.
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