Therapeutic efficacy of IL-2-loaded hydrogels in a mouse tumor model.
Interleukin-2 (IL-2) is a highly effective anticancer drug if it is applied locally for 5 consecutive days. In most cases this requires 5 invasive treatments, which is not usually acceptable for either the patient or the clinician. For this reason we have developed dextran-based hydrogels from which the required amount of encapsulated IL-2 (1-4 x 10(6) IU of IL-2) is gradually released during 5-10 days. Initially IL-2-containing macroscopic cylinder-shaped gels (implants), and later IL-2-containing injectable microspheres, were developed. These preparations were characterized in vitro, and the therapeutic activity was tested in DBA/2 mice with SL2 lymphosarcoma. The therapy was given to mice with a large and extensively metastasized tumor load (at least 5% of the body weight). If 1-4 x 10(6) IU of IL-2 was slowly released from the hydrogels over a period of 5-10 days, the therapeutic effects were very good and comparable to the effects of free IL-2 injections for 5 consecutive days. In conclusion, dextran-based hydrogels are promising systems for the controlled release of IL-2.
De Groot
Cornelis J
CJ
Faculty of Veterinary Medicine, Department of Cell Biology and Histology, Utrecht University, Utrecht, The Netherlands.
Cadée
Jenny A
JA
Koten
Jan-Willem
JW
Hennink
Wim E
WE
Den Otter
Willem
W
D000818:Animals; D003911:Dextrans / Q000008:administration & dosage; D005260:Female; D020100:Hydrogels; D007376:Interleukin-2 / Q000008:administration & dosage*; D008689:Methacrylates / Q000008:administration & dosage; D051379:Mice; D008811:Mice, Inbred DBA; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*
D003911:Dextrans; D020100:Hydrogels; D007376:Interleukin-2; D008689:Methacrylates; C005044:hydroxyethyl methacrylate