title: Monolithic precolumns as efficient tools for guiding the design of nanoparticulate drug-delivery formulations.
abstract: The development of nanomedicines for improved diagnosis and treatment of diseases is pushing current analytical methods to their limits. More efficient, quantitative high-throughput screening methods are needed to guide the optimization of promising nanoparticulate drug delivery formulations. In response to this need, we present herein a novel approach using monolithic separation media. The unique porosity of our capillary monolithic precolumns allows the direct injection and online removal of protamine-oligonucleotide nanoparticles ("proticles") without column clogging, thus avoiding the need for time-consuming off-line sample workup. Furthermore, ring-opening metathesis polymerization (ROMP)-derived monoliths show equivalent preconcentration efficiency for the target drug vasoactive intestinal peptide (VIP) as conventional particle-packed precolumns. The performance of the ROMP-derived monolithic precolumns was constant over at least 100 injections of crude proticle-containing and 300 injections of highly acidic samples. Applying a validated LC-MS/MS capillary monolithic column switching method, we demonstrate the rapid determination of both drug load and in vitro drug release kinetics of proticles within the critical first 2 h and investigate the stability of VIP-loaded proticles in aqueous storage medium intended for inhalation therapy.
authors.affiliation: Joanneum Research, HEALTH, Elisabethstrasse 5, 8010 Graz, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Gatschelhofer
authors.forename: Agnes
authors.initials: A
authors.lastname: Prasch
authors.forename: Michael R
authors.initials: MR
authors.lastname: Buchmeiser
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Karin
authors.initials: K
authors.lastname: Wernig
authors.forename: Martin
authors.initials: M
authors.lastname: Griesbacher
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sinner
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry; D016062:Porosity; D011479:Protamines / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D009841:Oligonucleotides; D011479:Protamines; D014660:Vasoactive Intestinal Peptide