Nanomedicine

 

PEGylated nanoliposomes loaded with an active agent are widely used in nanomedicine. We are studying the structures and morphology of PEGylated nanoliposomes before and after remote loading with drugs. Using solution X-ray scattering combined and our advanced analysis tools, we have studied the PEGylated liposomal doxorubicin (PLD) products like Doxil®, where remote doxorubicin loading is performed by a gradient of ammonium salts.  The PLD structures were compared with drug-free nanoliposomes having identical composition. We can determine the membrane electron density profiles of the empty and loaded PLDs, the thickness and density of the PEG layers, and the structure of the drug inside the liposomes. The structure of the drug inside the liposomes depend on the type of ammonium salt used for loading (BBA General Subject 2016). The information obtained by our measurements and analysis were essential for addressing the requirements of the FDA. Similar structures can be used for treatment of inflammatory neurodegenerative diseases (PLoS One 2015) or for loading more than one drug (vincristine and topotecan, Journal of Controlled Release 2012).

Doxil
Illustration of the structure of Doxil® and its generics as determined by our SAXS and WAXS analyses. The headgroups of HSPC and the phosphoethanolamine moiety of the DSPE–PEG are shown in blue and their acyl tails are drawn in red, PEG chains are in cyan, cholesterol molecules are in turquoise, and the unit cells of doxorubicin are shown in bourdeaux. The illustration is drawn to scale as indicated by the scale bar and was created by Einav Raviv.

Cationic lipids can be complexed with DNA and used for gene delivery applications. MT coated by a lipid bilayer can switch between nanotubes with either open or closed ends with lipid caps. This can be done by controlling the cationic lipid/tubulin stoichiometry and the ratio of the macromolecular areas of lipid to MT. These structure might be used for applications involving controlled chemical and gene encapsulation, and release (PNAS 2005Philos. Trans. A Math. Phys. Eng. Sci., 2006, Biophys. J 2007).