Nanoparticles Based on a Hydrophilic Polyester with a Sheddable PEG Coating for Protein Delivery

作者：Samadi Neda; van Steenbergen Mies J; van den Dikkenberg Joep B; Vermonden Tina; van Nostrum Cornelus F; Amidi Maryam; Hennink Wim E^*

来源：Pharmaceutical Research, 2014, 31(10): 2593-2604.

DOI：10.1007/s11095-014-1355-x

• biodegradable
• nanoparticles
• polyethylene glycol (PEG)
• protein release
• shedding

Purpose To investigate the effect of polyethylene glycol (PEG) in nanoparticles based on blends of hydroxylated aliphatic polyester, poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and PEG-PLGHMGA block copolymers on their degradation and release behavior.
Methods Protein-loaded nanoparticles were prepared with blends of varying ratios of PEG-PLGHMGA (molecular weight of PEG 2,000 and 5,000 Da) and PLGHMGA, by a double emulsion method with or without using poly(vinyl alcohol) (PVA) as surfactant. Bovine serum albumin and lysozyme were used as model proteins.
Results PEGylated particles prepared without PVA had a zeta potential ranging from similar to -3 to similar to-35 mV and size ranging from similar to 200 to similar to 600 nm that were significantly dependent on the content and type of PEG-block copolymer. The encapsulation efficiency of the two proteins however was very low (<30%) and the particles rapidly released their content in a few days. In contrast, all formulations prepared with PVA showed almost similar particle properties (size: similar to 250 nm, zeta potential: similar to-1mV), while loading efficiency for both model proteins was rather high (80-90%). Unexpectedly, independent of the type of formulation, the nanoparticles had nearly the same release and degradation characteristics. NMR analysis showed almost a complete removal of PEG in 5 days which explains these marginal differences.
Conclusions Protein release and particle degradation are not substantially influenced by the content of PEG, likely because of the fast shedding of the PEG blocks. These PEG shedding particles are interesting system for intracellular delivery of drugs.

• 出版日期2014-10