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

• Published in: Journal of controlled release Vol. 43; no. 1; pp. 65 - 74
• Main Authors: Liu, Lin-Shu, Liu, Shu-Qin, Ng, Steven Y, Froix, Michael, Ohno, Tadao, Heller, Jorge
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.01.1997; Elsevier
• Subjects: Alginate; Antineoplastic agents; Biological and medical sciences; Chitosan; Controlled delivery; Immunotherapy; Interleukin; Medical sciences; Pharmacology. Drug treatments; Controlled delivery; Alginate; Chitosan; Interleukin; Immunotherapy; Human; Microsphere; Pharmaceutical technology; Controlled release form; Cytokine; Cytotoxicity; Alginates; In vitro; Interleukin 2; T-Lymphocyte; Dosage form; Oside polymer; Tumor cell
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(96)01471-X

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 CaCl 2 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/CaCl 2, 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.