Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors.
Localized activation of the prodrug ifosfamide in or close to tumors by implanting encapsulated ifosfamide-activating cells is an efficacious strategy for tumor therapy. The aim of this study was to evaluate the feasibility of subsieve-size agarose capsules for enclosing the cells in this application. Compared with many conventional microcapsules, subsieve-size agarose capsules are about one-tenth the size and have both higher mechanical stability and allow better molecular exchangeability than other systems. Cells that have been genetically modified to express cytochrome P450 2B1 enzyme were encapsulated in subsieve-size agarose capsules of approximately 90 microm in diameter and implanted into preformed tumors in nude mice. Living cells were detected for >1 month after encapsulation in vitro and showed enzymatic activity (i.e., they were able to activate ifosfamide). More significant regression of preformed tumors was observed in the recipients implanted with cell-enclosing capsules compared with those implanted with empty capsules. These results suggest that the strategy of using subsieve-size agarose capsules enclosing cytochrome P450 2B1-expressing cells is feasible for tumor therapy by chemotherapeutic targeting in combination with ifosfamide administration.
Sakai
Shinji
S
Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. sakai@chem-eng.kyushu-u.ac.jp
Kawabata
Kenji
K
Tanaka
Shinji
S
Harimoto
Norifumi
N
Hashimoto
Ichiro
I
Mu
Changjun
C
Salmons
Brian
B
Ijima
Hiroyuki
H
Kawakami
Koei
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001703:Biophysics / Q000379:methods; D002415:Cats; D002460:Cell Line; D048429:Cell Size; D002470:Cell Survival; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010078:Oxazines / Q000494:pharmacology; D010316:Particle Size; D012685:Sepharose / Q000737:chemistry / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D010078:Oxazines; C014180:resorufin; D012685:Sepharose; D019362:Cytochrome P-450 CYP2B1; D007069:Ifosfamide