Local delivery system of immune modulating drug for unresectable adenocarcinoma: in vitro experimental study and in vivo animal study.
The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.
Lee
Don Haeng
DH
Department of Internal Medicine, Inha University, College of Medicine, Inchon, Korea.
Kang
Sung-Gwon
SG
Jeong
Seok
S
Yoon
Chang Jin
CJ
Choi
Jung-Ah
JA
Byun
Ju Nam
JN
Park
Jae Hyung
JH
Lee
Kyu Back
KB
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004343:Drug Implants; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010844:Picibanil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011076:Polycarboxylate Cement; D011140:Polyurethanes
D000970:Antineoplastic Agents; D004343:Drug Implants; D007155:Immunologic Factors; D008567:Membranes, Artificial; D011076:Polycarboxylate Cement; D011140:Polyurethanes; C005506:polycarbonate; D010844:Picibanil