Poly(lactic-co-glycolic acid) (PLGA) is a copolymer based on glycolic acid and lactic acid. The two monomer units are linked together by
ester linkages and form linear polyester chains. The obtained product is biodegradable and biocompatible, and it is approved
by the Food and Drug Administration (FDA) for production of various therapeutic devices as well as for drug delivery applications.
The properties of PLGA can be tuned by the ratio of the two monomers and by its molar mass distribution.
The characterization of PLGA by means of conventional size-exclusion chromatography (SEC) is problematic because of the lack
of suitable calibration standards. In addition, the linear polyester structure can be modified by the addition of small amounts
of polyfunctional monomer to obtain branched chains of differing degrees of branching. The degree of branching becomes an
additional parameter that can be used to adjust PLGA properties — all of which renders conventional column calibration an
inadequate analytical technique.
In this application note, two commercially available samples were analyzed by SEC coupled to a multi-angle light scattering
(MALS) detector (HELEOS), a refractive index detector (Optilab rEX), and a viscosity (VIS) detector (ViscoStar). The ViscoStar
was used in order to discover additional information about the molecular structure of the analyzed polymers. In addition to
molar mass distributions, the SEC–MALS-VIS system yields the relationship between intrinsic viscosity and molar mass (Mark-Houwink
plot) that can provide deep insight into the molecular structure of the polymers being analyzed.
Figure 1: Differential molar mass distribution curves of two PLGA samples.
In Figure 1, the molar mass distributions are given as differential distribution plots. As seen from the plots, the two samples
span markedly different molar mass ranges. The Mark-Houwink plots of the two samples are shown in Figure 2 together with the
plot of linear polystyrene that is shown simply for the sake of comparison. The slope of the Mark-Houwink plot of the linear
polystyrene is 0.71, a typical value for linear random coils in thermodynamically good solvents. The slope of the red sample
roughly corresponds to a linear structure as well. However, there is a slight indication of deviation from linearity at the
region of high molar masses that may indicate the presence of branched molecules. The Mark-Houwink plot of the blue sample
is curved. Curvature of the Mark-Houwink plot generally reveals branching. In addition, the slope of the higher molar mass
portion of the Mark-Houwink plot of 0.48 suggests significant branching.
Figure 2: Mark-Houwink plots of two samples of PLGA (red and blue) and linear polystyrene (magenta). The lines are linear
extrapolations of the data.
SEC-MALS-VIS is an excellent method for the characterization of PLGA polyesters as it has the ability to determine not only
the molar mass distribution, but to reveal subtle differences in PLGAs molecular structure.
Wyatt Technology Corporation
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