Paclitaxel distribution in poly(ethylene glycol)/poly(lactide-co-glycolic acid) blends and its release visualized by coherent anti-Stokes Raman scattering microscopy

Abstract

Mechanisms underlying the release of paclitaxel (PTX) from poly(ethylene glycol)/poly(lactic-coglycolic acid) (PEG/PLGA) blends were investigated by coherent anti-Stokes Raman scattering (CARS) microscopy. PLGA, PEG, and PTX were selectively imaged by using the resonant CARS signal from the CH 3 , CH 2 , and aromatic CH stretch vibrations, respectively. Phase segregation was observed in PLGA films containing 10 to 40 wt.% PEG in the absence of PTX loading. The PEG phase existed in the form of crystalline fibers in the (8:2, weight ratio) and (7:3) PLGA/PEG films. CARS observation indicated that PTX preferentially partitioned into the PEG domains in the (9:1) and (8:2) PLGA/PTX films, but exhibited a uniform mixing with both PLGA and PEG in the (7:3) PLGA/PEG film. The solid dispersion of PTX into PEG domains was attributed to a strong interaction between PTX and PEG, supported by the disappearance of PEG crystallization in the PTX-loaded PLGA/PEG film evidenced through X-ray diffraction analysis. PTX release was induced by exposing the film to an aqueous solution and monitored in real time by CARS and two-photon fluorescence microscopy. Fast dissolution of both PEG and PTX was observed at the film surface. Upon infiltration of water into the film, the PEG domains rearranged into ring structures enriched by both PTX and PEG. The CARS data provided a visual evidence explaining the accelerated burst release followed by more sustained release of PTX from the PLGA/PEG films as measured by HPLC.

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

“…37 Raw DPPE-PEG showed the presence of strong peaks at 19° and 23° 2Θ, a small peak at 21° 2Θ, and smaller broad peaks above 25° 2Θ. The peaks at 19°, 23°, and above 25° 2Θ are similar to previous results for PEG powder, 46 whereas the peak at 21° 2Θ corresponds to the presence of a phospholipid bilayer. Upon spray-drying, the peaks above 25° 2Θ disappeared, whereas the peaks at 19° and 23° 2Θ remained for all formulated particle systems.…”

The influence of additives in modulating drug delivery and degradation of PLGA thin films

“…[57][58][59][60] The preferential association of PCTX with PEG was observed by coherent anti-stokes Raman scattering microcopy by Kang et al, 61 and this association was validated by the disappearance of the sharp crystallization peaks of PEG under XRD in the presence of PCTX. 61 Here, the association between PCTX and PEG was qualified by the strong positive correlations between the parallel release of PCTX and PEG (Figure 8). This correlation also showed a dependence on the concentration of the PEG additives, particularly with PEG10k.…”

Blends of Paclitaxel with POSS-Based Biodegradable Polyurethanes: Morphology, Miscibility, and Specific Interactions

“…Recently, Kang et al investigated the paclitaxel distribution in PLGA/PEG blends by selectively imaging the three components using coherent anti-Stokes Raman scattering (CARS) microscopy. 27 In the 9:1 and 8:2 PLGA/PEG films, they not only observed that paclitaxel preferentially partitioned into the PEG domains in the blends, but also found that the strong interactions between paclitaxel and PEG prevented the crystallization of PEG. Moreover, they observed a uniform mixing of paclitaxel in both PLGA and PEG in PLGA/PEG (7:3) films.…”