Self-assembly Of ?-cyclodextrin Conjugated Poly(glycerol Methacrylate) Derivatives By Host–guest Inclusion Complexation For Potential Applications In Drug Delivery

Upon reflection,PGMA-based polymers have been playing a significant role in the process of the development of polymer self-assembly.Multiple functionalized PGMA derivatives with thermosensitivity,pH-responsiveness,luminescence emission or other properties,have been synthesized by the combination of living radical polymerization,ring-opening addition,and click chemistry to meet different requirements of constructing stimuliresponsive self-assembly architectures.The self-assembly methods tend to be more flexible with the introduction of supramolecular chemistry.Being one of the most widely used supramolecular hosts,cyclodextrins(CDs)are donut-shaped cyclic oligosaccharides,and the relatively hydrophobic interior cavity endows CD the ability to complex with a wide range of lipophilic guest molecules possessing suitable polarity and dimension characteristics.To date,numerous kinds of vesicles have been prepared not only from conventional block copolymers,but also based on these host-guest interactions.Compared to conventional lipidbased vesicles(liposomes),polymer vesicles possess better mechanical stabilities,controllable surface functionality,and tunable wall thickness and chemical properties.Reverse vesicles,as the counterparts of normal vesicles formed in aqueous solution,are spherical containers consisting of a hydrophobic core surrounded by a reverse bilayer,whose hydrophobic portions are exposed to nonpolar solvents both in the core and in the exterior.More importantly,their physical and biological properties can be further modulated through molecular engineering,endowing them with low polydispersity and good responsiveness towards external stimuli such as pH,light,enzyme,voltage or a combination.To date,numerous kinds of vesicles have been prepared not only from conventional block copolymers,but also based on these host–guest interactions.In this study,we focused on the formation of polymeric vesicles and reverse polymeric from supramolecular amphiphiles based on host-guest interactions between multiple CD-grafted host and guestpolymers,i.e.,non-covalent cross-linking,ensuring their great potential for use in drug delivery systems,by means of the natural excellent performance of polymeric vesicles.We first developed a facile synthesis of pseudo-graft amphiphilic copolymer reverse vesicles based on poly(glycerol methacrylate)(PGMA)and cholesterol(Chol)-ended linear polylactide(PLA-Chol)via ?-CD-Chol host-guest interactions.Through a “dissolve-dialysis” method,the pseudo-graft amphiphilic copolymers self-assembled into reverse vesicles.Congo red extraction experiment demonstrated the excellent loading capacities of reverse vesicles,showing great potential as carriers,especially for hydrophilic drugs.In order to realize controlled release of drugs,azobenzene(Az)involved well-defined polymeric vesicles was designed.Hydrophobic Az grafted PGMA(PGMA-Az)and hydrophilic CD grafted PGMA(PGMA-CD)derivatives have been synthesized to direct interpolymer host–guest complexation.These polymeric vesicles demonstrated an excellent stability.In the presence of Na2S2O4,however,the N=N bonds of Az groups can be reduced so that the polymeric vesicles disassembled in some degree.The results revealed that the disassociation of the polymeric vesicles was advantageous to the release of macromolecular drugs,exhibiting only moderate burst release.We believe the polymeric vesicles hold a great potential in the delivery of colon-specific macromolecular drugs,especially biomacromolecules such as proteins and nucleic acids.