Drug delivery is a large and growing research area that involves both synthetic and natural polymers. A number of polymers are being developed for different purposes, such as to conjugate or contain small and large molecule drugs to release at a specified rate. Complexes of polymer and drug are used to customize release rates, achieve targeting, and improve half-life in order 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 (polylactic acid), PEO (polyethylene oxide), and PLC (polycaprolactone) are commonly used in these applications due 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/conformation will all affect polymer degradation, and thus its drug release and bioavailability. These properties must be measured for both 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 processes before clinical use.
Size-exclusion chromatography (SEC), also known as gel-permeation chromatography (GPC) is a well-known and widely used technique for measuring polymer molecular weight. With SEC a concentration detector is always used, typically a refractive index (RI) detector. Multi-detector SEC measurements expand on this by adding detectors such as light-scattering (LS) or viscometry (IV). LS can measure absolute molecular weight, independent of a molecules shape, structure, chemistry, or conformation. A viscometer allows the measurement of intrinsic viscosity (IV), which is used to study conformation and branching, which can expose structural changes that the polymer may undergo.
Typical analytical SEC measurements can take approximately 25 to 45 minutes and consume 25 to 45 mL of mobile phase. This is time-consuming and can be expensive if working with organic and halogenated solvents. Advanced Polymer Chromatography™ (APC) uses novel SEC column technologies with robust, small particles (<3 µm) to achieve better sample resolution using smaller columns. This increases productivity, while significantly reducing runtime and cost. An additional benefit of the reduced solvent usage is to effectively make APC a ‘greener’ technology than traditional analytical SEC.
Combining multi-detector SEC and APC has been challenging due to the significance of inter-detector band broadening (or dispersion). However, recent developments in integrated multi-detector systems allows up to four detectors to be connected to the ACQUITY APC System with only a minimal loss of resolution due to band broadening. Malvern Panalytical recently introduced a version of the OMNISEC REVEAL advanced detector system that through collaboration with Waters, has been optimized for integrated use under APC conditions.
In this application note, Malvern Panalytical’s OMNISEC REVEAL multi-detector module was combined with Waters ACQUITY APC System to offer high resolution, rapid multi-detector SEC characterization of a PLA-PEO-PLA drug delivery polymer. The molecular properties of a virgin sample were compared with two samples sterilized by radiation.
