Sustained-release interleukin-12 microspheres in the treatment of cancer.
Interleukin-12 (IL-12) is a recently discovered cytokine with tremendous antitumor potential. It has been shown to boost the host immune response against experimental cancers in animal models. However, most studies have utilized IL-12 in the solution form, necessitating frequent dosing with higher doses, consequently leading to issues of toxicity. The only attempts at sustaining release have been in the production and use of genetically engineered cells that can secrete IL-12 constantly. These attempts are cost prohibitive and involve extensive labor. This study demonstrates the use of biodegradable albumin microspheres to sustain the release of IL-12. In vitro release of IL-12 from the microspheres was found to fit Higuchi's square-root-of-time model, suggesting diffusion-mediated release. About 46% of the theoretical IL-12 content was released slowly over a period of 24 hr. When administered intraperitoneally to C57BL/6 mice bearing subcutaneous melanomas, the microspheres significantly prolonged the survival when administered at half the weekly dose of the solution formulation. The microsphere dosage form also resulted in generally lower levels of liver and kidney function enzymes, suggesting lower toxicity.
Shah
A U
AU
Department of Pharmaceutical Sciences, Southern College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
D'Souza
M J
MJ
D000418:Albumins / Q000737:chemistry*; D000818:Animals; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy*; D013154:Spleen / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000418:Albumins; D003692:Delayed-Action Preparations; D018664:Interleukin-12