A New Insight for an Old System: Protein-PEG Colocalization in Relation to Protein Release from PCL/PEG Blends

Abstract

Quantification of protein-polymer colocalization in a phase-separated polymer blend gives important insights into the protein release mechanism. Here, we report on the first visualization of protein-poly(ethylene glycol) (protein-PEG) colocalization in poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) blend films using a combined application of confocal Raman mapping and confocal laser scanning microscopy (CLSM) imaging. The degree of protein-PEG colocalization was further quantified via a novel image processing technique. This technique also allowed us to characterize the 3-D protein distribution within the films. Our results showed that the proteins were homogeneously distributed within the film matrix, independent of PEG content. However, the degree of protein-PEG colocalization was inversely proportional to PEG content, ranging from 65 to 94%. This quantitative data on protein-PEG colocalization was used along with in vitro PEG leaching profile to construct a predictive model for overall protein release. Our prediction matched well with the experimental protein release profile, which is characterized by an initial burst release and a subsequent slower diffusional release. More importantly, the success of this predictive model has highlighted the influence of protein-PEG colocalization on the protein release mechanism.

In situ microscopic studies on the structures and phase behaviors of SF/PEG films using solid-state NMR and Raman imaging

“…[6][7][8][9][10] Before the use of the blend materials, the structures and phase behaviors of the blend system were thought to be essential issues because they affected the properties of the products. 17,18 In addition, microfocus XRD was also used for the morphological study. In addition, the clearance of PEG from body is dependent on the molecular weight.…”

Cenderitide-Eluting Film for Potential Cardiac Patch Applications

“…As we observed no significant film degradation from our degradation study, we believe that subsequent release over 30 days was due to diffusion controlled release of hydrophilic CD-NP diffusing out of hydrophobic polymer matrix. The slow degrading characteristics of PCL [31], [32]and the diffusion release from PCL [33] had been reported in literature respectively. All films displayed sustained release over time in the range of 12–84 µg/mL (for 0–6 hours) and 1–6 µg/mL (for 1–30 days).…”

Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using electrospinning

“…At each releasing time, the cumulative amounts of HP from PCL/PEG = 1:4 membrane, released in the first hour (P < 0.01 relative to GEM), had a high initial burst 80% and reached maximal cumulative release of nearly 98% within 24 h. Whereas, compared to HP in the first hour, GEM within PCL/PEG = 9:1 membrane showed relatively slow drug release in the first hour (50%). The significant difference of releasing kinetics between HP and GEM was observed within 24 h, as indicated drug-releasing rate can be regulated within 24 h by adjusting PEG and PCL compositions, then both drugs complete releasing occurred during the time span between 24 h and 72 h. The mechanism of drug release was reported by Liu et al [32] and Lei et al [14] that PEG acted as a pore former in PCL/PEG blends, where the releasing rate from co-localization of protein/drug and blends were proportional to PEG content. The hydrophilic PEG in PCL/PEG blends easily acted on aqueous solution, which resulted in the formation of swollen structure and subsequently increased the drug-releasing rate, as indicated the kinetics of drug releasing was mainly due to the degradation of the PCL/PEG blends [14].…”