TY - JOUR
T1 - Sustained release of IL-1Ra from biodegradable microspheres prolongs its IL-1-neutralizing effects
AU - Lavi, Galia
AU - Dinarello, Charles A.
AU - Apte, Ron N.
AU - Cohen, Smadar
PY - 2005/11/29
Y1 - 2005/11/29
N2 - A sustained delivery system for interleukin-1 receptor antagonist (IL-1Ra) may have great therapeutic and industrial potential due to the cytokine activity as an IL-1 inhibitor. Here, we investigated the capability of biodegradable polymeric microspheres to sustain the release and prolong the therapeutic efficacy of IL-1Ra. IL-1Ra was encapsulated within rapidly degrading poly(lactic/glycolic acid) PLGA RG502H microspheres, which showed a desirable release profile of IL-1Ra in vitro. Pharmacokinetic study in mice revealed elevated serum levels of the recombinant IL-1Ra (rIL-1Ra) for up to 8 days following subcutaneous injection of IL-1Ra microspheres. In comparison, the serum levels of rIL-1Ra following subcutaneous or intravenous bolus injection of the soluble cytokine decreased very rapidly; within 48 h no recombinant cytokine was detected in mice sera. The sustained delivery of rIL-1Ra for over two weeks was efficient in inhibiting IL-1β-stimulated induction of serum IL-6. These results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-1Ra within PLGA RG502H microspheres.
AB - A sustained delivery system for interleukin-1 receptor antagonist (IL-1Ra) may have great therapeutic and industrial potential due to the cytokine activity as an IL-1 inhibitor. Here, we investigated the capability of biodegradable polymeric microspheres to sustain the release and prolong the therapeutic efficacy of IL-1Ra. IL-1Ra was encapsulated within rapidly degrading poly(lactic/glycolic acid) PLGA RG502H microspheres, which showed a desirable release profile of IL-1Ra in vitro. Pharmacokinetic study in mice revealed elevated serum levels of the recombinant IL-1Ra (rIL-1Ra) for up to 8 days following subcutaneous injection of IL-1Ra microspheres. In comparison, the serum levels of rIL-1Ra following subcutaneous or intravenous bolus injection of the soluble cytokine decreased very rapidly; within 48 h no recombinant cytokine was detected in mice sera. The sustained delivery of rIL-1Ra for over two weeks was efficient in inhibiting IL-1β-stimulated induction of serum IL-6. These results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-1Ra within PLGA RG502H microspheres.
UR - http://www.scopus.com/inward/record.url?scp=27844520492&partnerID=8YFLogxK
U2 - 10.1560/DYBG-TWDV-J8PF-7W9T
DO - 10.1560/DYBG-TWDV-J8PF-7W9T
M3 - Article
AN - SCOPUS:27844520492
SN - 0021-2148
VL - 45
SP - 457
EP - 464
JO - Israel Journal of Chemistry
JF - Israel Journal of Chemistry
IS - 4
ER -