Physiological change after local injection of liposomes containing tumor necrosis factor (TNF).
After the local (subcutaneous) administration of tumor necrosis factor-alpha (TNF), two types of physiological change were clearly observed in dogs. One was a systemic change, the other was a local change at the injected site. Solution, negatively charged liposome and positively charged liposome were locally injected in dogs. Even with local administration, the increase of triglyceride in plasma and the decrease of blood pressure were the most serious after administration of the solution. These changes were typical systemic side effects of TNF. Consequently, liposomes suppressed these serious systemic side effects of TNF after a local administration. Another physiological change was irritation at the injected site. However, after administration of positively charged liposome, the lowest irritation at the injected site was observed, along with the highest local concentration of TNF. We reported the superior antitumor effect of positively charged liposomes in solution, as well as the lowest systemic circulation after an intratumor administration. Therefore, it was speculated that a positively charged liposome directly acted on the tumor cells without TNF release. These results exhibited the potency of liposomal delivery of TNF with local administration.
Yasui
K
K
Department of Formulation Research, Dainippon Pharmaceutical Co., Ltd., Fukushimaku, Osaka, Japan.
Nakamura
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004337:Drug Carriers; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007022:Hypotension / Q000139:chemically induced; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha