Poly(lactic-co-glycolic acid) (PLGA) is a copolymer based on lactic acid and glycolic acid. The two monomer units are connected together by ester linkages and develop linear polyester chains. The end product is biocompatible and biodegradable, and is approved by the Food and Drug Administration (FDA) for production of a variety of therapeutic devices as well as for drug delivery applications. PLGA properties can be tuned by the ratio of the two monomers and by the total molar mass distribution.
The characterization of PLGA using conventional size exclusion chromatography (SEC) is difficult due to lack of appropriate calibration standards. Furthermore, the linear polyester structure can be altered by adding small quantities of polyfunctional monomer to attain branched chains of varying degrees of branching. The degree of branching becomes an extra parameter that can be used to alter PLGA properties—all of which renders conventional column calibration a poor analytical method.
Analysis
In this article, two commercially available samples were studied in the ASTRA® software by SEC coupled to a differential viscosity detector (ViscoStar®), a Multi-Angle Light Scattering (MALS) detector (DAWN®), and a refractive index detector (Optilab®). The MALS and RI signals were integrated to find out the absolute molecular weight, independently of column calibration or elution time. The ViscoStar was used to measure intrinsic viscosity (IV) and uncover more information regarding the molecular structure of the tested polymers. Besides molar mass distributions, the SEC-MALS-IV system yields the association between intrinsic viscosity and molar mass (Mark-Houwink-Sakurada plot) that can offer a better understanding about the molecular structure of the polymers being studied.
The molar mass distributions are shown as differential distribution plots in Figure 1. As seen from the plots, the two samples span distinctly different molar mass ranges. Figure 2 shows the Mark-Houwink-Sakurada plots of the two samples, along with the plot of linear polystyrene illustrated for comparison purpose. The slope of the Mark-Houwink-Sakurada plot of the linear polystyrene is 0.71 – a normal value for linear random coils in thermodynamically good solvents. The slope of the red sample approximately corresponds to a linear structure as well, but there is a slight hint of deviation from linearity at the region of high molar masses that may specify the presence of branched molecules. The Mark-Houwink-Sakurada plot of the blue sample is curved. Curvature of the Mark-Houwink-Sakurada plot usually reveals branching. Furthermore, the slope of the higher molar mass portion of the Mark-Houwink-Sakurada plot of 0.48 indicates substantial branching.
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Figure 1. Differential molar mass distribution curves of two PLGA samples.
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Figure 2. Mark-Houwink-Sakurada plots of two samples of PLGA (red and blue) and linear polystyrene (magenta). The lines are linear extrapolations of the data.
Conclusion
SEC-MALS-IV is an exceptional technique for the characterization of PLGA polyesters as it has the ability to establish the absolute molar mass distribution as well as reveal slight differences in PLGA’s molecular structure.
This information has been sourced, reviewed and adapted from materials provided by Wyatt Technology.
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