The Study Of The Cell-membrane Mimetic Polymersome As Drug Carrier

Polymersomes, self-assembled vesicles of amphiphilic copolymers, usually possess an aqueous interior separated from the outside by the hydrophobic membrane with both external and internal surfaces formed by hydrophilic shells. In recent years, this unique morphology has attracted considerable attention due to their potential applications in biomedicine as drug and gene delivery carriers, artificial cells and bioreactors. However, the utilization of the polymersome as carriers for various therapeutic agents may be the most promising. In this paper, we synthetized diblock copolymers based on phosphorylcholine molecules and studied their self-assembly behavior to construct cell membrane mimetic polymersomes. The potential application of such biocompatible polymersomes as durg carriers was also explored. The main work in this paper foucses on the construction and the formation mechanism of cell-membrane mimetic polymersomes, and the degradation-induced controllable release:(1) The poly(D,L-lactide)-block-poly(2-methacryloyloxyethyl phosphorylcholine)(PLA-b-PMPC) was specially designed to develop biomimetic giant polymersomes and nano-sized polymersomes via a simple spontaneous assemble in aqueous solution. The weight fraction of the hydrophilic PMPC block (fPC) was proved to play an important role in the size and morphology control of the self-assembled aggregates. The large polymersomes with controlled micro-meter size and biomimetic PMPC corona have great potential as artificial cell models. The nano-sized polymersomes can be used as drug carriers for cancer therapy.(2) For polymersomes to achieve their potential as effective delivery vehicles, they must efficiently encapsulate therapeutic agents into either the aqueous interior or the hydrophobic membrane. Cell membrane-mimetic polymersomes were prepared from amphiphilic PLA-b-PMPC diblock copolymers and were used as encapsulation devices for water-soluble molecules. Thioalkylated zwitterionic phosphorylcholine protected quantum dots (PC@QDs) were chosen as hydrophilic model substrates and successfully encapsulated into the aqueous polymersome interior, as evidenced by transmission electron microscopy (TEM) and flow cytometry. In addition, we also found a fraction of the PC@QDs was bounded to both the external and internal surfaces of the polymersome. This interesting immobilization might be due to the ion-pair interactions between the phosphorylcholine groups on the PC@QDs and polymersomes. The experimental encapsulation results support amechanism of PLA-b-PMPC polymersome formation, in which PLA-b-PMPC copolymer chains first form spherical micelles, then worm-like micelles, and finally disk-like micelles which close up to form polymersomes.(3) Nano-sized biocompatible and biodegradable polymersomes were prepared based on PLA-b-PMPC diblock copolymers and applied for the release anti-cancer drugs. Hydrophobic doxorubicin (DOX) and hydrophilic doxorubicin hydrochloride (DOX·HCl) were successfully loaded into the polymersome membrane and polymersome interior, respectively. The in vitro release studies demonstrated that the release of DOX and DOX·HCl from polymersomes was highly pH-dependent, i.e. significantly faster drug release at mildly acidic pH of5.0compared to physiological pH7.4. Furthermore, DOX·HCl-loaded polymersomes exhibited faster drug release than DOX-loaded polymersomes under the same pH conditions. The highly pH-depended release behavior was attributed to the hydrolysis of PLA-b-PMPC, which would result in morphological transformation from polymersome to micelle with a triggered release of the encapsulated drugs. The drug-loaded polymersomes were shown to rapidly enter HepG2cells, localize in their endosome/lysosomes with acidic pH environment and display enhanced intracellular release of the drugs into the cytosol. These biocompatible and acid pH-sensitive polymersomes might have great potential for cancer therapy.(4) PEO and PMPC are biocompatible polymers that have delivered clinically proven benefits in various biomedical applications. Biocompatible polymer polymersomes were prepared on basis of the inclusion complexation between α-cyclodextrins (α-CDs) and double-hydrophilic PEO-b-PMPC in aqueous media without using organic solvent. The supramolecular structure of the nano-sized vesicles was demonstrated by transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The biocompatibility of PEO-b-PMPC block copolymers and PEO-b-PMPC/a-CDs vesicles were studied by cell viability test, and the results revealed that both of them showed excellent cytocompatibility. Hydrophilic doxorubicin (DOX·HCl) was successfully loaded into the vesicle with loading content of10.3%and loading efficiency of30%. The DOX·HCl loaded vesicles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into HepG2cells as confirmed by fluorescence microscope (FM). With these properties, the polymer vesicles are attractive as drug carriers for pharmaceutical applications.