title: Asymmetrical flow field-flow fractionation and multiangle light scattering for analysis of gelatin nanoparticle drug carrier systems.
abstract: The physicochemical properties of nanosized colloidal drug carrier systems are of great influence on drug efficacy. Consequently, a broad spectrum of analytical techniques is applied for comprehensive drug carrier characterization. It is the primary objective of this paper to present asymmetrical flow field-flow fractionation (AF4), coupled online with multiangle light scattering detection, for the characterization of gelatin nanoparticles. Size and size distribution of drug-loaded and unloaded nanoparticles were determined, and data were correlated with results of state-of-the-art methods, such as scanning electron microscopy and photon correlation spectroscopy. Moreover, the AF4 fractionation of gelatin nanoparticulate carriers from a protein model drug is demonstrated for the first time, proposing a feasible way to assess the amount of loaded drug in situ without sample preparation. This hypothesis was set into practice by monitoring the drug loading of nanoparticles with oligonucleotide payloads. In this realm, various fractions of gelatin bulk material were analyzed via AF4 and size-exclusion high-pressure liquid chromatography. Mass distributions and high-molecular-weight fraction ratios of the gelatin samples varied, depending on the separation method applied. In general, the AF4 method demonstrated the ability to comprehensively characterize polymeric gelatin bulk material as well as drug-loaded and unloaded nanoparticles in terms of size, size distribution, molecular weight, and loading efficiency.
authors.affiliation: Abbott GmbH & Co. KG, Department Pharmaceutical Development, Knollstrasse, 67008 Ludwigshafen, Germany. wolfgang.fraunhofer@abbott.com
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fraunhofer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.forename: Conrad
authors.initials: C
authors.lastname: Coester
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000302:isolation & purification; D031521:Fractionation, Field Flow / Q000379:methods*; D005780:Gelatin / Q000737:chemistry* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008027:Light; D049329:Nanostructures; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D012031:Refractometry; D012542:Scattering, Radiation; D013552:Swine
chemical_list: D004337:Drug Carriers; D007074:Immunoglobulin G; D009841:Oligonucleotides; D016179:Granulocyte Colony-Stimulating Factor; D005780:Gelatin