TY - JOUR
T1 - Sustained delivery of IL-1Ra from biodegradable microspheres reduces the number of murine B16 melanoma lung metastases
AU - Lavi, Galia
AU - Voronov, Elena
AU - Dinarello, Charles A.
AU - Apte, Ron N.
AU - Cohen, Smadar
N1 - Funding Information:
Smadar Cohen holds the Claire & Harold Oshry Professor Chair in Biotechnology. Ron N. Apte is supported by the Israel Science Foundation and the German–Israeli DIP collaborative program. Elena Voronov is supported by the Israel Cancer Association and the Concern Foundation.
PY - 2007/11/6
Y1 - 2007/11/6
N2 - The interleukin-1 receptor antagonist (IL-1Ra) is approved for treating rheumatoid arthritis and has the potential to treat metastatic cancers involving excess amounts of the pro-inflammatory cytokine, interleukin-1β (IL-1). To maintain sustained delivery and improve its therapeutic efficacy, IL-1Ra was encapsulated with stabilizers in biodegradable poly-(lactic/glycolic acid) (PLGA) microspheres. In vitro cytokine release and bioactivity studies in cultured melanoma B16 cells revealed the microspheres to be capable of sustained IL-1Ra release on a daily level that could inhibit cell proliferation for at least 7 days. The level of IL-1Ra released from the microspheres was revealed in rat serum. Significant amounts of IL-1Ra were released over the course of 2 weeks, at levels sufficient for the inhibition of exogenously-administered IL-1β. In mice injected with B16 melanoma cells, the sustained IL-1Ra delivery from biodegradable microspheres inhibited tumor growth and significantly prolonged mice survival. Furthermore, the tumors were less vascularized and after amputation of the primary tumor, the number of lung metastases was reduced by 70%, as compared to the control groups. Thus, we show that biodegradable microspheres represent an efficient system for sustaining IL-1Ra delivery and improving its therapeutic efficacy. As such, the system can be integrated into therapeutic protocols for treating metastatic cancers.
AB - The interleukin-1 receptor antagonist (IL-1Ra) is approved for treating rheumatoid arthritis and has the potential to treat metastatic cancers involving excess amounts of the pro-inflammatory cytokine, interleukin-1β (IL-1). To maintain sustained delivery and improve its therapeutic efficacy, IL-1Ra was encapsulated with stabilizers in biodegradable poly-(lactic/glycolic acid) (PLGA) microspheres. In vitro cytokine release and bioactivity studies in cultured melanoma B16 cells revealed the microspheres to be capable of sustained IL-1Ra release on a daily level that could inhibit cell proliferation for at least 7 days. The level of IL-1Ra released from the microspheres was revealed in rat serum. Significant amounts of IL-1Ra were released over the course of 2 weeks, at levels sufficient for the inhibition of exogenously-administered IL-1β. In mice injected with B16 melanoma cells, the sustained IL-1Ra delivery from biodegradable microspheres inhibited tumor growth and significantly prolonged mice survival. Furthermore, the tumors were less vascularized and after amputation of the primary tumor, the number of lung metastases was reduced by 70%, as compared to the control groups. Thus, we show that biodegradable microspheres represent an efficient system for sustaining IL-1Ra delivery and improving its therapeutic efficacy. As such, the system can be integrated into therapeutic protocols for treating metastatic cancers.
KW - Biodegradable microspheres
KW - IL-1Ra
KW - Melanoma B16 tumor
KW - Metastatic cancer
KW - Sustained release
UR - http://www.scopus.com/inward/record.url?scp=35248871058&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2007.07.015
DO - 10.1016/j.jconrel.2007.07.015
M3 - Article
C2 - 17900737
AN - SCOPUS:35248871058
SN - 0168-3659
VL - 123
SP - 123
EP - 130
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -
