Nanoparticle stability in biologically relevant media: influence of polymer architecture

Abstract

We have contrasted the behavior of nanoparticles formed by the self-assembly of polymers based on poly(ethylene glycol) (PEG) and poly(D,L-lactide), with linear, linear-dendritic and bottle-brush architectures in biologically relevant media. Polymer PEG content ranged between 14% and 46% w/w, and self-assembly was triggered by a rapid and large change in solvent quality inside a four-stream vortex mixer. We examined nanoparticle interaction with human serum albumin (HSA), and solute release in the presence of fetal bovine serum. Dynamic light scattering data showed that PEG surface brushes of all nanoparticles provided effective steric stabilization, thus limiting their interaction with human serum albumin. Calorimetric experiments revealed that nanoparticle-HSA interaction was relatively weak and enthalpically driven, whereas dynamic light scattering results of incubated nanoparticles showed the absence of larger aggregates for most of the polymers examined. Solute core partitioning was examined by the loss of Forster resonance energy transfer (FRET) from a core-loaded donor-acceptor pair. The rate and magnitude of FRET efficiency loss was strongly dependent on the polymer architecture, and was found to be lowest for the bottle-brush, attributed to its covalent nature. Collectively, these findings are expected to impact the molecular design of increasingly stable polymeric carriers for drug delivery applications.

Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin

“…The fluorescence intensity of HSA was quenched by the addition of NPs indicating binding between NPs and HAS . After 5 min of incubation, the largest decrease in HSA maximum fluorescence intensity was exhibited by non‐PEGylated NPs ( P < 0.05).…”

“…[26,27] The tubes were incubated at 37°C in a Thermomixer (Comfort; Eppendorf, Germany) shaking horizontally at 100 rpm. At set time points (15,30,45, 60 min, 2, 4, 6, 12, 24, 48 h), the tubes were centrifuged at 13 000 rpm for 5 min (to separate NPs from release medium). A separate tube was prepared for each time point.…”

“…Shifts in NP size distribution curves were indicative of protein adsorption onto NPs and possible NP aggregation. [37,45] Figure 5 illustrates that for all samples except NPs without PEG, there was a small shift in median particle size after 1-h incubation in human serum, indicating the absence of observable complexing and aggregation. On the other hand, non-PEGylated NPs showed significant shifts of the size distribution curve to higher median size values.…”

“…The fluorescence intensity of HSA was quenched by the addition of NPs indicating binding between NPs and HAS. [29,42,45] After 5 min of incubation, the largest decrease in HSA maximum fluorescence intensity was exhibited by non-PEGylated NPs (P < 0.05). Samples of all PEGylated NPs exhibited an insignificant change in HSA maximum fluorescence intensity (P > 0.05) as illustrated in Figure 6.…”

Real-time Ratiometric Imaging of Micelles Assembly State in a Microfluidic Cancer-on-a-chip

“…Recently, a Förster Resonance Energy Transfer (FRET) based approach has been used to follow the disassembly of supramolecular assemblies in blood serum, [13]- [16] and in animal models, [17] by encapsulation or covalent attachment of a FRET fluorophore pair into one micelle. In a recent work we employed PEG-Dendron amphiphiles that were functionalized with a spectral-shifting coumarin to track the stability of micelles in serum and cells.…”