Hyaluronic acid hydrogel as Nogo-66 receptor antibody delivery system for the repairing of injured rat brain: in vitro.
Nogo-66 and NgR are important receptors inhibiting neuronal regeneration and therefore are targets for treating CNS injury. Antagonists of this receptor including blocking antibodies are potential therapeutic agents for CNS axonal injuries such as spinal cord and brain trauma. A new antibody (IgG) releasing system has been developed by covalently attaching IgG to the biodegradable hyaluronic acid (HA) hydrogel via the hydrolytically unstable hydrazone linkage, aiming to deliver the antibody of CNS regeneration inhibitors to the injured brain. In this paper we describe the synthesis, physico-chemical characteristics and test results of biological activity of antibody released from hyluronic acid hydrogel. To form the conjugates the antibody is attached to the polymer backbone using a condensation reaction between aldehyde group of the antibody and hydrazide group of the HA hydrogel. Furthermore, pH sensitive linkage-hydrozone has been formed between hydrogel and antibody. The amount of conjugated antibodies can reach 135 microg antibody/mg hydrogel in the dry state. At low pH, the antibodies released quite fast. However, the antibodies released much slower in neutral and alkaline environment. The bioactivity of antibody released from hydrogel was retained as demonstrated by indirect immunofluorescence technique.
Tian
W M
WM
Biomaterials Laboratory, Department of Materials Science and Engineering Tsinghua University, Beijing 100084, P.R. China.
Zhang
C L
CL
Hou
S P
SP
Yu
X
X
Cui
F Z
FZ
Xu
Q Y
QY
Sheng
S L
SL
Cui
H
H
Li
H D
HD
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000008:administration & dosage* / Q000276:immunology*
D000906:Antibodies; D058851:GPI-Linked Proteins; D020100:Hydrogels; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; D006820:Hyaluronic Acid