methylcellulose and Carcinoma-256--Walker

The purpose of this study was to reveal the effectiveness of the polymer coated liposomes as a carrier of the anticancer drug doxorubicin in intravenous administration. The size controlled doxorubicin-loaded liposomes (egg phosphatidylcholine : cholesterol = 1:1 in molar ratio) were coated with hydrophilic polymers (polyvinyl alcohol; PVA and hydroxypropylmethylcellulose; HPMC) having a hydrophobic moiety in the molecules (PVA-R, HPMC-R). The existence of a thick polymer layer on the surface of the polymer coated liposomes was confirmed by measuring the change in particle size and the amount of polymer on the liposomal surface. The polymer coating effects on the tumor accumulation of the drug encapsulated in the liposomes were evaluated in Walker rat carcinoma 256 cell bearing rats. The doxorubicin-loaded liposomes coated with PVA-R and HPMC-R showed higher drug accumulation into the tumor site by prolonging the systemic circulation in tumor-bearing rats. The targeting efficiency of the polymer coated liposomes calculated with the total and tumorous clearance of the drug was ca. 5 times larger than that of non-coated liposomes. We ascertained that polymers having a hydrophobic moiety in the molecule such as PVA-R and HPMC-R are suitable materials for modifying the surfaces of the doxorubicin-loaded liposome to improve its targeting properties.

Topics: Animals; Antibiotics, Antineoplastic; Area Under Curve; Carcinoma 256, Walker; Doxorubicin; Drug Carriers; Lactose; Liposomes; Male; Methylcellulose; Neoplasm Transplantation; Oxazines; Particle Size; Polyvinyl Alcohol; Rats; Rats, Wistar

In this study we have used tissue culture techniques to explore the mechanism by which metastatic cancer cells in the bone marrow interfere with erythropoiesis. The effect of transplantable Walker-256 (W256) cancer cells on Ep-stimulated erythroid colony formation (CFU-E) in methylcellulose cultures and 59Fe-heme synthesis by rat marrow cells in suspension cultures was studied. The number of CFU-Es per 4 X 10(5) marrow cells decreased by 55% in the presence of 4 X 10(2) cancer cells. Likewise, the stimulatory effect of Ep on normal marrow heme synthesis decreased by 89% when cancer cells were added to marrow cell cultures. By the immobilization of the cancer cells in an agar underlayer, the inhibitory effect of cancer cells on marrow erythropoiesis in an upper methylcellulose layer was demonstrated to be independent of cell contact. The CFU-E growth-inhibitory effect of cancer cells could be attenuated by drugs which interfere with cancer cell protein and DNA synthesis. Although these experiments suggest that cancer cells produce an inhibitor of erythropoiesis, a stable inhibitory factor was not isolated. In similar experiments, rat peritoneal macrophages were also able to inhibit in vitro erythropoiesis. We conclude that cancer cells have the capacity to inhibit erythropoiesis by a mechanism which is independent of cell contact.

Topics: Animals; Carcinoma 256, Walker; Cells, Cultured; Colony-Forming Units Assay; Culture Media; Erythropoiesis; Hematopoietic Stem Cells; Heme; Macrophages; Methylcellulose; Rats; Rats, Inbred Strains

Topics: Animals; Carcinoma 256, Walker; Female; Lymphoma, Non-Hodgkin; Methylcellulose; Rats