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Gatschelhofer, C; Prasch, A; Buchmeiser, MR; Zimmer, A; Wernig, K; Griesbacher, M; Pieber, TR; Sinner, FM.
Monolithic precolumns as efficient tools for guiding the design of nanoparticulate drug-delivery formulations.
Anal Chem. 2012; 84(17):7415-7421 Doi: 10.1021/ac3012208
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Leading authors Med Uni Graz
Gatschelhofer Christina
Sinner Frank Michael
Co-authors Med Uni Graz
Pieber Thomas
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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.
Find related publications in this database (using NLM MeSH Indexing)
Chromatography, High Pressure Liquid -
Drug Carriers - chemistry
Nanomedicine -
Nanoparticles - chemistry
Oligonucleotides - chemistry
Porosity -
Protamines - chemistry
Tandem Mass Spectrometry -
Vasoactive Intestinal Peptide - chemistry

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