Effects of Polyethylene Glycol Spacer Length and Ligand Density on Folate Receptor Targeting of Liposomal Doxorubicin In Vitro

The folate receptor is an attractive target for selective tumor delivery of liposomal doxorubicin (DXR) because it is abundantly expressed in a large percentage of tumors. This study examined the effect of polyethylene glycol (PEG) spacer length and folate ligand density on the targeting ability of folate-modified liposomes. Liposomes were modified with folate-derivatized PEG-distearoylphosphatidylethanolamine with PEG molecular weights of 2000, 3400, or 5000. The association of DXR-loaded liposomes with KB cells, which overexpress the folate receptor, was evaluated by flow cytometry at various ratios of folate modification. A low ratio of folate modification with a sufficiently long PEG chain showed the highest folate receptor-mediated association with the cells, but did not show the highest in vitro cytotoxicity. DXR release from folate-modified liposomes in endosomes might be different. These findings will be useful for designing folate receptor-targeting carriers

A MECHATRONIC CASE STUDY HIGHLIGHTING THE NEED FOR RE-THINKING THE DESIGN APPROACH

Developing mechatronic products is a great challenge for many companies due to the multi-disciplinary nature of the development process. In this article the main objective is an investigation of seven aspects related to the synthesis process of developing mechatronic products. The role and effects of these aspects are illustrated by a case study. A literature study is performed regarding how well the seven aspects have been covered in the literature. It reveals that some suggestions for support can be found in terms of semi-formal modelling suggestions and proposal for procedures, but that the context of the proposed support often originates from a control engineering dominated research area. This circumstance leaves a vast amount of other types of mechatronic products with only sparse development support with the potential of being made operational