title: Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production.
abstract: Gelatine nanoparticles (GNPs) are biodegradable and biocompatible drug delivery systems with excellent clinical performances. A two-step desolvation is commonly used for their preparation, although this methodology has several shortcomings: lack of reproducibility, small scales and low yields. A straightforward and more consistent GNP preparation approach is presented here focusing on the development of a one-step desolvation with the use of a commercially available gelatine type. Controlled stirring conditions and ultrafiltration are used to achieve large-scale production of nanoparticles of up to 2.6 g per batch. Particle size distributions are conserved and comparable to those determined for two-step desolvation on small scale. Additionally, a range of cross-linking agents is examined for their effectiveness in stabilising GNPs as an alternative to glutaraldehyde. Glyceraldehyde demonstrated outstanding properties, which led to high colloidal stability. This approach optimises the manufacturing process and the scale-up of the production capacity, providing a clear potential for future applications.
authors.affiliation: a Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics , Ludwig-Maximilians Universität München , Munich , Germany.
authors.forename: Katharina J
authors.initials: KJ
authors.lastname: Geh
authors.affiliation: a Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics , Ludwig-Maximilians Universität München , Munich , Germany.
authors.forename: Madlen
authors.initials: M
authors.lastname: Hubert
authors.affiliation: a Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics , Ludwig-Maximilians Universität München , Munich , Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D005976:Glutaral / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005780:Gelatin; D005976:Glutaral
keywords: AF4; Gelatine nanoparticles; cross-linking; one-step desolvation; scale-up