Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres

被引:185
作者
Liu, LS
Liu, SQ
Ng, SY
Froix, M
Ohno, T
Heller, J
机构
[1] ADV POLYMER SYST INC,RES INST,REDWOOD CITY,CA 94063
[2] INST PHYS & CHEM RES,TSUKUBA,IBARAKI 305,JAPAN
关键词
alginate; chitosan; controlled delivery; interleukin; immunotherapy;
D O I
10.1016/S0168-3659(96)01471-X
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Porous microspheres were formed by the gelation of two polysaccharides, a polyanionic sodium alginate and a polycationic chitosan, followed by lyophilization which creates the porous structure. Porous microspheres were also formed by gelation of sodium alginate with CaCl2 and gelation of sodium alginate with polylysine. FITC-BSA was incorporated into the microspheres by mixing the protein with the polysaccharide solution prior to gelation. Interleukin-2 (IL-2) was incorporated into the preformed microspheres by diffusion from an external aqueous solution of IL-2. Sustained release of the proteins from porous alginate/chitosan microspheres is of longer duration than from alginate/CaCl2, or from alginate/polylysine microspheres. Activity of the released IL-2 was investigated by determining the induction of cytotoxic T lymphocytes (CTL) when incubated with tumor cells and lymphocytes. It was found that the IL-2 remained active in the alginate/chitosan microspheres since the released IL-2 triggered induction of CTL. Further, IL-2 released in a sustained manner triggered induction of CTL more efficiently than free IL-2. Tumor-killing specific activity of CTL was the same whether induced by the sustained released IL-2 or by the addition of free IL-2.
引用
收藏
页码:65 / 74
页数:10
相关论文
共 29 条
[21]  
ROSENBERG SA, 1984, CANCER TREAT REP, V68, P233
[22]   OBSERVATIONS ON THE SYSTEMIC ADMINISTRATION OF AUTOLOGOUS LYMPHOKINE-ACTIVATED KILLER CELLS AND RECOMBINANT INTERLEUKIN-2 TO PATIENTS WITH METASTATIC CANCER [J].
ROSENBERG, SA ;
LOTZE, MT ;
MUUL, LM ;
LEITMAN, S ;
CHANG, AE ;
ETTINGHAUSEN, SE ;
MATORY, YL ;
SKIBBER, JM ;
SHILONI, E ;
VETTO, JT ;
SEIPP, CA ;
SIMPSON, C ;
REICHERT, CM .
NEW ENGLAND JOURNAL OF MEDICINE, 1985, 313 (23) :1485-1492
[23]  
ROSENBERG SA, 1987, NEW ENGL J MED, V316, P789
[24]  
SANDFORD PA, 1987, IND POLYSACCHARIDES, P363
[25]   CHARACTERIZATION OF ALBUMIN-ALGINIC ACID COMPLEX COACERVATION [J].
SINGH, ON ;
BURGESS, DJ .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1989, 41 (10) :670-673
[26]   EFFECT OF N-ACETYLCHITO-OLIGOSACCHARIDES ON ACTIVATION OF PHAGOCYTES [J].
SUZUKI, K ;
TOKORO, A ;
OKAWA, Y ;
SUZUKI, S ;
SUZUKI, M .
MICROBIOLOGY AND IMMUNOLOGY, 1986, 30 (08) :777-787
[27]  
TOPALIAN SL, 1989, J IMMUNOL, V142, P3714
[28]  
WALLACE PK, 1993, CANCER RES, V53, P2358
[29]   LYSIS OF HUMAN PANCREATIC ADENOCARCINOMA CELLS BY AUTOLOGOUS HLA-CLASS-I-RESTRICTED CYTOLYTIC T-LYMPHOCYTE (CTL) CLONES [J].
WOLFEL, T ;
HERR, W ;
COULIE, P ;
SCHMITT, U ;
ZUMBUSCHENFELDE, KHM ;
KNUTH, A .
INTERNATIONAL JOURNAL OF CANCER, 1993, 54 (04) :636-644