Gelatin/chondroitin 6-sulfate microspheres for the delivery of therapeutic proteins to the joint.
OBJECTIVE
To develop a biodegradable, inflammation-responsive microsphere system for the intraarticular delivery of therapeutic proteins.


METHODS
Microspheres were synthesized by complex coacervation. Radiolabeled protein release and microsphere degradation were assessed by exposing the microspheres to human synovial fluids (SF) and recombinant gelatinase. Microsphere degradation was confirmed by scanning electron microscopy (SEM). Microsphere biocompatibility was evaluated in vitro by incubating the microspheres with human synoviocytes, and in vivo by injection into mouse joints.


RESULTS
Optimal microsphere formulation was developed. Significant (up to 100%) release of encapsulated protein occurred in SF samples with measurable metalloprotease activity, while release was minimal in SF with negligible activity. Dissolution of microspheres exposed to gelatinase was confirmed by SEM. Microspheres were found to be noncytotoxic in vitro, and noninflammatory in vivo.


CONCLUSIONS
Microsphere encapsulation is an inflammation-responsive and biocompatible system of protein delivery that holds promise for use in the delivery of therapeutic proteins to the joint.
Brown
K E
KE
University of Maryland, College Park, USA.
Leong
K
K
Huang
C H
CH
Dalal
R
R
Green
G D
GD
Haimes
H B
HB
Jimenez
P A
PA
Bathon
J
J
D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001672:Biocompatible Materials / Q000008:administration & dosage; D002809:Chondroitin Sulfates / Q000008:administration & dosage*; D017364:Collagenases / Q000378:metabolism; D016503:Drug Delivery Systems; D005780:Gelatin / Q000008:administration & dosage*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007270:Injections, Intra-Articular; D007700:Kinetics; D008666:Metalloendopeptidases / Q000494:pharmacology; D008863:Microspheres; D010003:Osteoarthritis / Q000188:drug therapy; D013582:Synovial Fluid / Q000187:drug effects / Q000201:enzymology
D001672:Biocompatible Materials; D005780:Gelatin; D002809:Chondroitin Sulfates; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases