Application of asymmetric flow field-flow fractionation (AF4) and multiangle light scattering (MALS) for the evaluation of changes in the product molar mass during PVP-b-PAMPS synthesis

Joel Castillo,Catalina Fuentes,Jose Vila,Lars Nilsson

doi:10.1007/s00216-018-1039-1

Abstract

The use of polymers for the delivery of drugs has increased dramatically in the last decade. To ensure the desired properties and functionality of such substances, adequate characterization in terms of the molar mass (M) and size is essential. The aim of this study was to evaluate the changes in the M and size of PVP-b-PAMPS when the amounts of the synthesis reactants in the two-step radical reaction were varied. The determination of the M and size distributions was performed by an asymmetric flow field-flow fractionation (AF4) system connected to multiangle light scattering (MALS) and differential refractive index (dRI) detectors. The results show that the M of the polymers varies depending on the relative amounts of the reactants and that AF4-MALS-dRI is a powerful characterization technique for analyzing polymers. Using AF4, it was possible to separate the product of the first radical reaction (PVP-CTA) into two populations. The first population had an elongated, rod-like or random coil conformation, and the second had a conformation corresponding to homogeneous spheres or a microgel structure. PVP-b-PAMPS had only one population, which had a rod-like conformation. The molar masses of PVP-CTA and PVP-b-PAMPS found in this study were higher than those reported in previous studies.

Highlights

In recent decades, the use of polymers as a means of drug delivery has increased
The physical and mechanical properties of polymers depend on the molecular architecture, molar mass (M), size, and distributions [5]
1-Vinyl-2-pyrrolidinone (VP), 2,2'-azobis(2-methylpropionitrile) (AIBN), 2-dodecylsulfanylthiocarbonylsulfanyl-2-methyl propionic acid (DMP), tetrahydrofuran (THF), 2-acrylamido-2methyl-1-propanesulfonic acid (AMPS), N,Ndimethylformamide (DMF), acetone, and diethyl ether were purchased from Sigma-Aldrich (Sigma Aldrich, MO, USA)

Summary

Introduction

The use of polymers as a means of drug delivery has increased. Polymeric micelles have become an attractive option because of their capability to protect andThe physical and mechanical properties of polymers depend on the molecular architecture, molar mass (M), size, and distributions [5]. The most commonly used separation method for polymers is size exclusion chromatography (SEC) In this technique, the size and M can be estimated either with a standard calibration curve or by absolute determination of both the M and average size by utilizing online multiangle light scattering (MALS) in combination with concentration determination via, for instance, differential refractive index (dRI) detection. SEC has some limitations, which include the adsorption of sample components to the column, the degradation of large species due to shear forces in the column, and the co-elution effects that can arise, for instance, from the presence of branches in the polymers [6,7,8] This can produce abnormal elution effects that make the determination of the M distribution difficult or impossible [8, 9]

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