Chemical imaging of drug eluting coatings: combining surface analysis and confocal Raman microscopy

Abstract

Chemical images of the surfaces and the interiors of coatings of rapamycin in poly(lactic-co-glycolic acid) (PLGA) obtained by mass spectrometry and light scattering methods reveal a three dimensional picture of the chemical morphology of drug eluting coatings before, during, and after drug elution. The coating formulations examined ranged from 5 to 50 wt.% rapamycin in PLGA with and without a top layer ("capcoat") of PLGA. Surface sensitive electron spectroscopy for chemical analysis (ESCA) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) indicated that the outer surface of the coatings (without a PLGA capcoat) were drug-rich prior to elution. TOF-SIMS depth profiling using SF5+ polyatomic primary ions revealed a drug-enriched region at the near surface of the non-capcoated coatings ranging in thickness from 5 to 115 nm. The chemical morphology of the rapamycin/PLGA coatings on stents was determined using scanning confocal Raman microscopy, from the surface through the bulk of the coatings. Images of the coatings on stents showed a homogeneous distribution of rapamycin for the coatings with low concentrations of drug (5 wt.%) and more non-uniform distributions for higher concentrations of rapamycin (>25 wt.%). Images acquired from the interior of the films during the elution process indicated that rapamycin diffuses out of the coating but also segregates into drug-rich domains with increasing elution time. Optical interferometry measurements of coating thickness suggested that PLGA eroded from the coating during the elution experiment.