sorbitan-monooleate and Colonic-Neoplasms

To improve the anti-tumor effect of polyethylene glycol-modified liposome containing doxorubicin (DOX-PEG liposome), the effect of sequential administration of PEG-Span 80 niosome was investigated for Colon-26 cancer cells (C26)-bearing mice. The concept of the current study is as follows: Since both particulates would be accumulated in the tumor tissue due to the enhanced permeability and retention (EPR) effect, PEG-Span 80 niosome, mainly composed of synthetic surfactant (Span 80), would interact with DOX-PEG liposome and be a trigger to induce the release of DOX from the liposome within the tumor tissue, leading to the improvement of anti-tumor effect of DOX-PEG liposome. To find out an adequate liposome for this strategy, several PEG liposomes with different compositions were examined in terms of drug release enhancement and it was found that PEG-Span80 niosome could significantly enhance the release of calcein and DOX from a PEG liposome composed of 90% hydrogenated soybean phosphatidylcholine (HSPC) and 10% cholesterol. The sequential administration of PEG-Span 80 niosome at 24 or 48 h after dosing of DOX-PEG liposome provided a higher anti-tumor effect than the single dose of DOX-PEG liposome in the C26-bearing mice. Particularly, the 24 h-later dosing of PEG-Span 80 niosome has been found to be more effective than the 48 h-later dosing. It was also confirmed that the coexistence of PEG-Span 80 niosome with DOX-PEG liposome in 50% serum or in 50% supernatant of tumor tissue homogenate significantly increased DOX release from PEG liposome, suggesting that DOX release from DOX-PEG liposome within tumor tissue would be enhanced via the interaction with PEG-Span 80 niosome. This strategy would lead to the safer and more inexpensive chemotherapy, since it could make it possible to provide the better anti-tumor effect by utilizing the lower dose of DOX.

Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Cholesterol; Colonic Neoplasms; Doxorubicin; Drug Liberation; Hexoses; Liposomes; Mice; Mice, Inbred BALB C; Phosphatidylcholines; Polyethylene Glycols; Solvents; Surface-Active Agents

Span 80 (sorbitan monooleate) vesicles behaved differently from conventional phospholipid vesicles (liposomes) because the former had a more fluid interface. After doxorubicin hydrochloride (DOX) was encapsulated into the Span 80 vesicle (loading efficiency: 63 %), DOX-loaded Span 80 vesicles (DVs) were thereafter added to Colon 26 cells. It was suggested, from the flow cytometric analysis and confocal laser microscopic observation, that DVs directly deliver DOX into the cytoplasm of Colon 26 cells. DVs showed the different delivery manner from the DOX-loaded liposomes (DLs). It is considered that the difference of delivery manner between DVs and DLs resulted in the difference of cytotoxicity (IC(50)); i.e. IC(50) values for DVs and DLs were 5 and > 30 μM, respectively. The results obtained herein would give the fundamental findings which can contribute to the improvement of formulation of conventional liposome-based carrier and its cytotoxicity.

Topics: Animals; Cell Culture Techniques; Cell Line, Tumor; Colonic Neoplasms; Doxorubicin; Drug Delivery Systems; Female; Flow Cytometry; Hexoses; Liposomes; Mice; Microscopy, Confocal; Microscopy, Electron, Transmission; Tetrazolium Salts; Thiazoles; Transport Vesicles

The lectin Eucheuma serra agglutinin (ESA) is known from previous studies to specifically bind to high-mannose type N-glycans and to induce apoptotic cancer cell death in vitro. In this study, Span 80 vesicles, with an average diameter between about 200 and 400 nm, containing immobilized ESA were prepared from the nonionic surfactant Span 80, also known as sorbitan monooleate. The vesicles were investigated in vitro and in vivo to evaluate the vesicles's potential applicability as novel drug delivery system. The results obtained are promising since the following was observed: (i) vesicular ESA had the same hemagglutinating activity as free ESA, demonstrating its biological activity when bound to the vesicles; (ii) vesicles containing immobilized ESA decreased the viability of Colo201 cancer cells in vitro while the growth of normal cells was not affected; (iii) the vesicles showed binding to Colo201 cells in vitro and caused inhibition of cancer cell growth in nude mice to which the vesicle-treated cells were added; (iv) the vesicles diminished tumor growth after intravenous administration to nude mice which contained an implanted Colo201 tumor; (v) the vesicles showed a tendency to accumulate at the site of the tumor 6h after i.v. administration to nude mice. Thus, all measurements carried out indicate that this type of Span 80 vesicle can be considered as promising alternatives to conventional phospholipid-based vesicles.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Colonic Neoplasms; Drug Delivery Systems; Drug Screening Assays, Antitumor; Female; Hemagglutination Tests; Hexoses; Humans; Lectins; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Particle Size; Rhodophyta; Surface-Active Agents