Gel-permeation chromatography (GPC) is widely used for measuring the molecular weight (distribution) of polymers. Historically, the elution volume of an unknown sample was compared with that of known standards to estimate molecular weight. Advanced detection offers absolute molecular weight and branching analysis through intrinsic viscosity (IV) or Rg. In pharmaceutical research, correctly targeting the delivery location and release profile of drugs is a critical challenge and a great many avenues of research are being explored to overcome the challenges of drug delivery. Polymers are playing an increasing role in drug delivery applications as targeted controlled-release mechanisms. One potential solution is to conjugate chemotherapy drugs such as Doxorubicin (Dox) with a delivery polymer such as polyglutamate (PG). Preferential uptake of PG-Dox conjugates by cancer cells and local degradation and drug release could more effectively target cancer cells over healthy cells1. Advanced GPC can be used to study the conjugated polymer’s molecular weight, structure and conjugation levels to measure conjugated and free Dox, to predict efficacy vs toxicity. Poly(lactic acid) and poly(lactide-co-glycolide) are used in stents, biodegradable sutures and timed-release drug delivery applications. Structural analysis using IV can be combined with absolute molecular weight measurements to characterize the structural changes that accompany the compositional changes. In this presentation, we will show some novel analysis of PG-Dox polymer conjugate to assess its molecular weight, structure and the presence of free and conjugate Dox to gain additional insight into this conjugated drug delivery polymer. We will also show how IV and the Mark-Houwink plot can be used to characterize PLGA copolymer composition by comparison to known standards. Finally, we will show how these measurements help to understand changes in rheological properties of these polymers.

Applying multi-detector GPC/SEC to complex characterization of drug delivery polymers

255th National Meeting (2018)

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