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The Analytical Scientist / App Notes / 2018 / Advanced Polymer Chromatography to Evaluate Degradation of Drug Delivery Polymers

Advanced Polymer Chromatography to Evaluate Degradation of Drug Delivery Polymers

07/26/2018

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Abstract

In this note the degradation of a PLA-PEO-PLA drug delivery polymer was characterized.  Irradiated samples were seen to have dramatically reduced molecular weight but no changes in their conformation or structure implying that this degradation was due to polymer scission caused by the radiation.

Introduction

Drug delivery is a large and growing research area including the use of both synthetic and natural polymers. Various polymers are being used in different ways to conjugate or contain small and large molecule drugs to release at a specified rate. Complexes of polymer and drug are used to tailor release rates, achieve targeting, and improve half-life all to modulate the efficacy of the drug as a therapeutic. Defining the release profile of the drug is a critical parameter which relies in part on the degradation characteristics of the polymer. Polymers such as PLA (poly-lactic acid), PEO (poly-ethylene oxide), and polycaprolactone are commonly used in these applications thanks to their biocompatibility and biodegradability. In order to maximize the effectiveness of these drug-delivery polymers, their underlying molecular properties must be well-controlled as these will strongly impact their performance. Properties such as molecular weight, dispersity, and branching or conformation will all affect polymer degradation, and thus drug release and bioavailability. The properties must be measured for the virgin polymer and subsequent products made from it as the various processes undergone by the polymer will likely affect final properties. For example, any polymer to be used as a drug delivery implant will need to be sterilized by one or more potentially damaging treatments before clinical use.Size-exclusion chromatography (SEC), also known as gel-permeation chromatography (GPC) is a well-known and widely used tool for measuring polymer molecular weight. Multi-detector SEC measurements including refractive index (RI) and light scattering (LS) can measure absolute molecular weight, independent of a molecules shape, structure, chemistry, or conformation. Polymer concentration is measured by the RI detector alone. The addition of a viscometer allows the measurement of intrinsic viscosity (IV), which is used to study conformation and branching, and can expose any structural changes that the polymer may undergo.

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