Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II. Controlled release properties

Abstract

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. The aim of this work was to investigate the possibility of achieving the controlled release of a model protein, human serum albumin (HSA), from poly(ethylene glycol) (PEG)-coated biodegradable nanospheres (mean diameter of about 200 nm) prepared from amphiphilic diblock PEG-poly(lactic acid) (PLA) copolymers. HSA was efficiently incorporated into the nanospheres, reaching loadings as high as 9% (w/w). Results of the in vitro release studies showed that it is possible to control the HSA release by choosing the appropriate nanosphere size, loading, and composition. These results also revealed that, following their release, HSA molecules readsorbed onto the nanospheres surfaces when they were not protected by a PEG coating. We were surprised to observe that in spite of the water uptake of the PLA-PEG nanospheres [11-29% (w/w)], the copolymer did not significantly degrade after a 15-day incubation period. Therefore, we concluded that during this time HSA release from PLA-PEG nanospheres followed a diffusion mechanism where bulk erosion and surface desorption were negligible.

PEG–PLA microparticles for encapsulation and delivery of Tat-EGFP to retinal cells

“…2). This biphasic release profile is typical of PEG-PLA microparticles, and has been reported in the literature [30][31][32][33]. The initial burst phase is associated with the release of protein at the particle surface, while the sustained phase represents the slow diffusion of protein from the particle core and the slow release of protein as the particles degrade.…”

OX26 modified hyperbranched polyglycerol-conjugated poly(lactic-co-glycolic acid) nanoparticles: synthesis, characterization and evaluation of its brain delivery ability

“…Peak 3 was generated by the carbon of C=O. Figure 5c, d revealed the presence of two types of oxygen O=C (peak 4) at 532.0 eV and O-C (peak 5) at 533.5 eV, respectively [36]. Results indicated that OX26 is successfully conjugated onto EM-HPG-PLGA NPs, thus available for the interaction with the BBB.…”

Synthesis of novel biodegradable polyanhydrides containing aromatic and glycol functionality for tailoring of hydrophilicity in controlled drug delivery devices

“…Moreover, by synthesizing copolymers of aliphatic and aromatic monomers, precise control over the degradation rate can be achieved, from days to years. Unfortunately, increasing the aromatic content increases the hydrophobicity of the polymer, which may lead to protein aggregation along the hydrophobic domains inside the polymer matrix [1][2][3][4].…”

“…Therefore, our approach is to incorporate short oligo(ethylene glycol) (OEG) chains into polyanhydride monomers that will serve to reduce the hydrophobic polymer-protein interactions within the polymer matrix as well as allow further tuning of the degradation rate. Previous research has shown the beneficial effect of poly(ethylene glycol) (PEG) inclusion into block copolymers of polyesters such as e-caprolactone and lactide [2][3][4][5][6]. Polyanhydride copolymers of sebacic anhydride and PEG segments have been synthesized for pulsatile release and inhalation devices have been developed from prepolymers of sebacic acid and polyoxyethylene dicarboxylic acid.…”