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.

Use of monolithic supports for high‐throughput protein and peptide separation in proteomics

“…Most monolithic phases are created by polymerization or polycondensation (and sometimes both) of widely available monomeric compounds . One of the notable exceptions we noted is a paper describing ring opening metathesis polymerization to obtain monoliths for separation of nanoparticules that use somewhat expensive compounds and chemistry . It is undisputable that this technique has the ability of higher customization but also easier creation of columns more suitable for techniques like 2D‐LC.…”

“…Authors demonstrated that this technique can be employed to create 2D‐LC separation. The ability of monoliths allows easy creation and tailoring of solid phase, as well as easy column packing (as in a classical gravitational chromatography), combined with the reusability and high separation power (as those for HPLC) provides, from a chromatographer perspective, almost a golden ratio of traits . However, similar number of analysis can still be achieved by using less demanding equipment and pressures then with HPLC.…”

Monolithic chromatography in speciation analysis of metal-containing biomolecules: a review

“…[7][8][9] Poly(styrene-codivinylbenzene)-based monolithic columns have been successfully applied in the eld of proteomics for the rapid separation of peptides, proteins 12 and ribonucleic acids, 13 while the ringopening metathesis polymerization-derived monolithic anionexchangers were used for the analysis of double-stranded DNA fragments. [14][15][16] Furthermore, a successful application of the ring-opening metathesis polymerization-derived monolithic supports for their intended use as precolumns in capillary liquid chromatography for on-line removal of protamineoligonucleotide nanoparticles was reported by Gatschelhofer et al 17 Methacrylate-based monolithic stationary phases also enable fast and efficient analyses of biomolecules and nanoparticles, 18 they have been applied in purication of large plasmids and bacteriophages, 19,20 and offer chromatographic separation of proteins, 21,22 peptides, 23 nucleic acids 4 and low molecular mass organic acids. 24 Furthermore, methacrylate based monoliths are progressively used in the eld of proteomics.…”

Hydrophilic Polymer Monolithic Capillary Microextraction Online Coupled to ICPMS for the Determination of Carboxyl Group-Containing Gold Nanoparticles in Environmental Waters

“…Accordingly, polymer monolithic capillary microextraction (CME) has the advantages of low sample consumption, short analytical time, and easy online operation and, thus, has been widely applied in the separation and enrichment of inorganic ions, organic small molecules, and biological macromolecules. 23 Recent studies show that polymer monolithic CME is also useful for online screening of nanodrugs 24 and separation of biological nanoparticles, such as viruses, phages, and cells. 25 The above studies give us a hint that polymer monolithic CME has potential application in fast and online preconcentration of NPs.…”