Block-copolymers (BCP) are widely used building blocks in micelle and vesicle self-assembly as they can be tailored to match the required physical-chemical properties by varying the hydrophobic or hydrophilic block. These types of assemblies are used in drug delivery or cell mimicry as carriers for natural or synthetic active entities. We prepared a series of BCP with hydrophobic poly(cholesteryl methacrylate) (PCMA) with various hydrophilic extensions, such as poly(ethylene glycol) (PEG), 2-methacryloyloxyethyl phosphorylcholine (MPC), poly(dimethyl amino methacrylate) (PDMAEMA), poly(carboxyethyl acrylate) (PCEA) and poly(mathacrylic acid) (PMAA). PCMA is an interesting choice because cholesterol is natural compound and plays a vital role in the fluidity of cell membrane. The hydrophobic block length was synthesises with low PDI = 1.08 and molecular weights between 4-8 kDa. The hydrophilic extension were between 5 kDa to 20 kDa as determined from 1H NMR. The successful assembly of the HVs with BCPs homogenously distributed BCP in the membrane for both small HVs (Dh=150 nm) and giant HVs (d=2 μm) was shown through the FRET effect between the fluorescently labelled polymer chains and lipids. The stability of the assemblies was tested in different environments. i.e., upon pH change and by encapsulating into alginate beads. The intracellular fate of BCPs made with the polyanionic extensions was explored in HepG2 cells. Interestingly, the BCPs were retained in the cells over longer period compared to the lipids, when delivered as HVs. From a different perspective, HVs consisting of PCMA- PDMAEMA and lipids could be placed in the cytosol of RAW264.7 macrophages and used for intracellular nitric oxide production. Furthermore, micelles prepared of PCMA-PMPC and HVs assembled from PEG-PCMA and lipids showed excellent mucopenetrating capabilities evaluated in CaCo-2/HT29-MTX-E12 co-cultures and in a rat model. Taken together, BCPs with a PCMA hydrophobic block and varied hydrophilic extension offer unique opportunities in self-assembly of soft nanoparticles with promising applications in drug delivery and cell mimicry.

Polymer – lipid hybrid vesicles and micelles made of poly(cholesteryl methacrylate) containing amphiphilic block copolymers

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.