TY - JOUR
T1 - Development of Polymer Coacersome Structure with Enhanced Colloidal Stability for Therapeutic Protein Delivery
AU - Jo, Heejung
AU - Gajendiran, Mani
AU - Kim, Kyobum
N1 - Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle–particle charge interactions. Herein, a new term “coacersome” is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)-b-cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable “coacersome” structure. Water-soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP-2), and a sustained release profile up to 28 days. The BMP-2-loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.
AB - Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle–particle charge interactions. Herein, a new term “coacersome” is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)-b-cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable “coacersome” structure. Water-soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP-2), and a sustained release profile up to 28 days. The BMP-2-loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.
KW - bone morphogenetic protein 2
KW - coacersomes
KW - growth factor delivery
KW - methoxypolyethylene glycol attached PEAD
KW - osteogenic differentiation
UR - http://www.scopus.com/inward/record.url?scp=85074413041&partnerID=8YFLogxK
U2 - 10.1002/mabi.201900207
DO - 10.1002/mabi.201900207
M3 - Article
C2 - 31657524
AN - SCOPUS:85074413041
SN - 1616-5187
VL - 19
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 12
M1 - 1900207
ER -