title: Zinc-alginate microparticles for controlled pulmonary delivery of proteins prepared by spray-drying.
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.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Möbus
authors.forename: Jürgen
authors.initials: J
authors.lastname: Siepmann
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D000464:Alginates / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008168:Lung / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014961:X-Ray Diffraction; D019287:Zinc Sulfate / Q000737:chemistry*
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005079:Excipients; D006603:Hexuronic Acids; D020442:Poloxamer; D012710:Serum Albumin, Bovine; D019287:Zinc Sulfate; D020723:Glucuronic Acid