Suppression of in vivo tumor growth by using a biodegradable thermosensitive hydrogel polymer containing chemotherapeutic agent

Current systemic chemotherapy in the treatment of solid tumors inevitably induces various systemic adverse effects. Locally injected chemotherapy is expected to overcome this limitation of systemic therapy. We evaluated by luminescence imaging the effects of chemotherapy administered locally by means of a biodegradable thermosensitive hydrogel polymer. The human gastric cancer cell line HSC44Luc was used for tumor induction, and it was confirmed to be sensitive to doxorubicin by MTT assay. Cells were injected subcutaneously into Balb/c-nude mice. When the mean volume of tumor reached 400 mm(3), we divided the mice into 6 groups (5 per group) according to treatment: 1) control (intratumor injection of PBS), 2) systemic injection of doxorubicin, 3) intratumor injection of polymer gel, 4) intratumor injection of polymer gel physically mixed with a low dose of doxorubicin, 5) intratumor injection of polymer gel physically mixed with a high dose of doxorubicin, 6) intratumor injection of conjugated polymer gel with doxorubicin. Body weight and tumor volume were measured every 2 or 3 days for 30 days after treatment. One mouse in each group was sacrificed for histopathologic examination every week. Reductions in body weight were not significantly different among groups. The relative rate of tumor growth was 774% in Group 1, 267% in Group 2, 813% in Group 3, -186% in Group 4, and 155% in Group 6, respectively. Thus the relative rate of tumor growth in the groups treated with polymer gel mixed with doxorubicin and the groups treated with conjugated polymer gel with doxorubicin were lower than that in the control group. Locally injectable chemotherapy using a thermosensitive hydrogel polymer with doxorubicin can suppress tumor growth effectively without severe systemic toxicity.Bilensoy E, 2008, INT J PHARM, V347, P163, DOI 10.1016/j.ijpharm.2007.06.051Zhang J, 2007, ACTA BIOMATER, V3, P838, DOI 10.1016/j.actbio.2007.05.011Choi SW, 2007, J CONTROL RELEASE, V122, P24, DOI 10.1016/j.jconrel.2007.06.003Rapoport N, 2007, PROG POLYM SCI, V32, P962, DOI 10.1016/j.progpolymsci.2007.05.009Ankareddi I, 2007, INT J PHARM, V336, P241, DOI 10.1016/j.ijpharm.2006.11.065Kang GD, 2006, INT J PHARM, V319, P29, DOI 10.1016/j.ijpharm.2006.03.032Pison U, 2006, EUR J PHARMACOL, V533, P341, DOI 10.1016/j.ejphar.2005.12.068Ramanan RMK, 2006, BIOTECHNOL PROGR, V22, P118, DOI 10.1021/bp0501367Couffin-Hoarau AC, 2004, BIOMACROMOLECULES, V5, P2082, DOI 10.1021/bm0400527Ruel-Gariepy E, 2004, EUR J PHARM BIOPHARM, V57, P53, DOI 10.1016/S0939-6411(03)00095-XJohn AE, 2003, FASEB J, V17, P2296, DOI 10.1096/fj.03-0166fjeSong SC, 2003, J CONTROL RELEASE, V90, P303, DOI 10.1016/S0168-3659(03)00199-8Shapiro CL, 2001, NEW ENGL J MED, V344, P1997PARTRIDGE AH, 2001, J NATL CANC I MONOGR, V30, P135RATHI R, 2000ZENTNER GM, 1999, 9 INT S REC ADV DRUGRATHI R, 1999Contag CH, 1997, PHOTOCHEM PHOTOBIOL, V66, P523Jeong B, 1997, NATURE, V388, P860CHA Y, 1997LOWENTHAL RM, 1996, ONCOL CLIN N AM, V10, P967, DOI DOI 10.1016/S0889-8588(05)70378-6KLEINSZANTO AJ, 1992, PROG CLIN BIOL RES, V374, P167