Novel amphiphilic scorpion-like macromolecules (AScM) and amphiphilic star-like macromolecules (ASM): Physico-chemical characterizations and applications in stabilized colloidal drug delivery systems

AScMs and ASMs are two new series of amphiphilic macromolecules that have great potential as drug delivery systems. Both macromolecules form a core-shell micellar structure in aqueous medium, whereas AScMs aggregate to form polymeric micelles, and the ASMs have a covalently bound core structure and behave as unimolecular micelles.; AScMs have versatile structures that generate polymeric micelles with a wide range of CMC values (10-4-10-7 M), which influences their thermodynamic and kinetic stability. Some AScM polymeric micelles have free energy of micellization much lower than surfactant micelles (-23∼ -39 kJ/mol), and show slower dissociation kinetics upon drastic dilution. The ASM unimolecular micelles are inherently stable to temperature and concentration. Sizes of both micelles fall between 10∼20 nm in aqueous solution, which remained constant for 3 weeks at room temperature. Structural versatility of AScMs and ASMs also facilitate tailoring drug/micelle compatibility and drug loading. Hydrophobic drugs suloctidil and triclosan interact with the micellar systems differently: triclosan achieves 61% w/w loading within AScM M12P5 polymeric micelles and shows selectivity among micelles; whereas suloctidil had lower loadings without obvious selectivity. On the other hand, both drugs achieve 20-30% w/w loading within ASM unimolecular micelles. Differences in drug/micelle compatibility also result in rapid and sustained release kinetics for suloctidil and triclosan, respectively. Hemolytic activity evaluation concludes that AScMs with long acyl chains are hemolytic; whereas the ASMs are non-hemolytic due to the covalently bound core structures. Therefore, the ASMs are deemed more suitable as injectable drug delivery systems.; M12P5 can incorporated into DPPC liposomes to achieve steric stabilization. The incorporation of M12P5 into the DPPC bilayers is exothermic and spontaneous. Compared to unmodified DPPC vesicles, M12P5-DPPC liposomes maintain satisfactory colloidal stability, significantly reduce liposomal membrane permeability, and significantly inhibit in vitro cellular uptake by J774A.1 macrophages. Compared to PEG5000-DPPE which is widely used to prepare stabilized liposomes, M12P5 bind to the DPPC bilayers with greater affinity; upon dilution, M12P5-DPPC liposomes quantitatively retained incorporated M12P5 that ensures continued liposome-stabilization effect, whereas PEG5000-DPPE suffered significant loss. Therefore, M12P5 offers better alternative to PEG5000-DPPE to sterically stabilize DPPC liposomes.