Biodegradable Hybrid Block Copolymer – Lipid Vesicles as Potential Drug Delivery Systems

<p>The anticipated benefits of nano-formulations for drug delivery are well known: for nanomedicines to achieve this potential, new materials are required with predictive and tuneable properties. Excretion of excipients following delivery is advantageous to minimise the possibility of adverse effects; biodegradability to non-toxic products is therefore desirable. With this in mind, we aim to develop tuneable hybrid lipid-block copolymer vesicle formulations where the hydrophilic polymer block is polyethylene glycol (PEG), which has accepted biocompatibility, and the hydrophobic block of the polymer is biodegradable: polycaprolactone (PCL) or polylactide (PLA). We investigate five different block copolymers for the formation of 1:1 phospholipid:polymer hybrid vesicles, compare their properties to the appropriate unitary liposome (POPC) and polymersome systems and assess their potential for future development as nanomedicine formulations. The PEG-PCL polymers under investigation do not form polymersomes and exhibit poor colloidal and/or encapsulation stability in hybrid formulations with lipids. The properties of PEG-PLA hybrid vesicles are found to be more encouraging: they have much enhanced passive loading of a hydrophilic small molecule (carboxyfluorescein) compared to their respective polymersomes and exhibit more favourable release kinetics in the presence of serum compared to the liposome. Significantly, burst release from hybrid vesicles can be substantially reduced by making the polymer components of the hybrid vesicle a mixture containing 10 mol% of PEG<sub>16</sub>-PLA<sub>25</sub> that is intermediate in size between the phospholipid and larger PEG<sub>45</sub>-PLA<sub>54</sub> components. We conclude that hybrid lipid/PEG-PLA vesicles warrant further assessment and development as candidate drug delivery systems.</p>