Degradable Thermoresponsive
Nanogels for Protein Encapsulation
and Controlled Release
- Publication date
- Publisher
Abstract
Reversible addition–fragmentation chain transfer
(RAFT)
polymerization technique was used for the fabrication of stable core
cross-linked micelles (CCL) with thermoresponsive and degradable cores.
Well-defined poly(2-methacryloyloxyethyl phosphorylcholine), poly(MPC) <i>macro</i>RAFT agent, was first synthesized with narrow molecular
weight distribution via the RAFT process. These CCL micelles (termed
as nanogels) with hydrophilic poly(MPC) shell and thermoresponsive
core consisting of poly(methoxydiethylene glycol methacrylate) (poly(MeODEGM)
and poly(2-aminoethyl methacrylamide hydrochloride) (poly(AEMA) were
then obtained in a one-pot process by RAFT polymerization in the presence
of an acid degradable cross-linker. These acid degradable nanogels
were efficiently synthesized with tunable sizes and low polydispersities.
The encapsulation efficiencies of the nanogels with different proteins
such as insulin, BSA, and β-galactosidase were studied and found
to be dependent of the cross-linker concentration, size of protein,
and the cationic character of the nanogels imparted by the presence
of AEMA in the core. The thermoresponsive nature of the synthesized
nanogels plays a vital role in protein encapsulation: the hydrophilic
core and shell of the nanogels at low temperature allow easy diffusion
of the proteins inside out and, with an increase in temperature, the
core becomes hydrophobic and the nanogels are easily separated out
with entrapped protein. The release profile of insulin from nanogels
at low pH was studied and results were analyzed using bicinchoninic
assay (BCA). Controlled release of protein was observed over 48 h