Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization

Abstract

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-coated monodisperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (PLA) copolymers, with loadings up to 9% (w/w). Microscopic techniques and surface analysis studies enabled us to prove that the protein was well entrapped and not adsorbed onto the particle surface. Zeta potential and water uptake studies corroborated that part of the PEG chains are located in the nanosphere matrix. Water uptake in the nanospheres was related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. The hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA absorbed only about 10% (w/w). However, the rate of swelling at the beginning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG "brush" at the nanosphere surface drastically reduces HSA adsorption on the PEG-PLA nanospheres compared to the PLA ones.

Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI

“…Poly(lactic acid)-poly(ethylene glycol) block copolymer was prepared for use with the W/O/O particle formulation method. The PLA-PEG copolymer was prepared by ring opening polymerization of lactide in the presence of carboxymethyl-poly(ethylene glycol) (CM-PEG), using a procedure modified from Quellec and colleagues (31). Briefly, recrystallized DL-lactide monomer (Polysciences) was polymerized onto CM-PEG (molecular weight 3,400; Laysan Bio) in the presence of stannous 2-ethylhexanoate (Sigma) in toluene (anhydrous; Acros) at 110°C under a nitrogen atmosphere.…”

Drug transport to brain with targeted nanoparticles

“…59 It is likely that the [(water-in-oil) in water] solvent evaporation technique increases PEG entrapment, compared with the precipitation/solvent evaporation technique. 46 The water content of mPEG 5000 PLA 45000 nanoparticles (200 nm diameter) is around 30% compared with around 10% for PLA nanoparticles. 46 At room temperature and 37°C, a solid-like central core and more mobile interfacial region coexist within the PLA core of nanoparticles made of mPEG 5000 -PLA [glass transition temperature of around 333K], whereas the PEG corona layer situated on the nanoparticle surface is in the liquid phase.…”

“…Despite a higher water uptake the PLA or PLGA blocks of mPEG-PLA/ PLGA block copolymers have similar degradation behaviors. 45,46 mPEG blocks are released (10 -25% within 3 days and 30 -50% within 20 days at pH 7.4, 37°C) after cleavage of the ester bonds, [47][48][49] and, in the range of molecular weights of 1000 -20,000, are mainly excreted via the kidney. 50 Up to an extensive PLA/PLGA polymer degradation, nanoparticle morphology and size are generally preserved.…”

“…46 The water content of mPEG 5000 PLA 45000 nanoparticles (200 nm diameter) is around 30% compared with around 10% for PLA nanoparticles. 46 At room temperature and 37°C, a solid-like central core and more mobile interfacial region coexist within the PLA core of nanoparticles made of mPEG 5000 -PLA [glass transition temperature of around 333K], whereas the PEG corona layer situated on the nanoparticle surface is in the liquid phase. 67 The PLA chain packing density increases with the PLA molecular weights due to an increase in the number of attractive hydrophobic interactions between lactic acid units.…”

Surface Modification of Silica Nanoparticles to Reduce Aggregation and Nonspecific Binding

“…tissues, blood and single cells). [1][2][3][4][5][6][7][8][9][10][11] In microarray and microspot techniques, spatial resolution of individual reactive sites on a chip is extremely important. At the same time, improved labeling and detection technologies are required to analyze smaller sample volumes and to measure samples on a limited solid-phase area.…”