Co-Assembly of Biodegradable Comb-Dendritic Block Copolymers and Lipids for Functional Liposomes

A new series of biodegradable comb-dendritic block copolymers (CDPs) with a monodisperse alkyl-modified hydrophobic peptide block, poly(n-alkyl-D,L-glutamate), PADLG, and a hydrophilic polyester (PE) dendron block, were synthesized, and their co-assembly behavior with lipids was investigated using dynamic light scattering (DLS), confocal laser scanning microscopy (CLSM), and transmission electron microscopy (TEM). It has been found that during a certain window of CDP-lipid mix ratios, the CDPs favorably interact with the lipids to form “patchy” co-vesicles, characterized by CDP domains on the liposome surface, while macro-phase separation of the two species occurs outside of this window. Other factors such as assembly temperature, time, and the length and degree of saturation of the acyl tails of lipids, have also been found to strongly influence the miscibility and morphology of the CDP-lipid system. These unique lipid-dendrimer co-vesicles, or “lipodendrisomes”, offer great potential for biomedical applications involving functional colloidal structures, such as targeted liposomes for drug delivery and responsive vesicles.