ABSTRACT
It is still a major challenge for targeted cancer chemotherapy to design a stable biocompatible micellar drug delivery system. To address this dilemma, novel responsive cross-linked micelles (x-micelles) based on polyurethane with photo-responsive coumarin derivatives and pH-responsive hydrazone groups were synthesized. The polymers could be self-assembled into micelles using a typical and facile way. The x-micelles were stable at physiological conditions after UV light induced cross-linking, and can be disassociated under acidic condition. The drug loading content (DLC) and the encapsulation efficiency (EE) of the obtained x-micelles (15.2% and 60.8% respectively) were higher than those of micelles (9.8% and 39.2% respectively), and the DOX release rate of x-micelles was also improved. For targeted therapy, folic acid (FA) was then conjugated to x-micelles, resulting in x-micelles-FA. Cellular viability experiments show that both x-micelles and micelles had a low cytotoxicity and good biocompatibility of up to 1000 µg mL-1, and DOX-loaded x-micelles-FA and x-micelles exhibited half-maximal inhibitory concentration (IC50) values of 1.17 and 2.40 µg mL-1, respectively, to HeLa cells, but have lower cytotoxicity to L929 cells. The pH-responsive x-micelles-FA exhibited superior extracellular stability but activated intracellular drug release. We have demonstrated that the polyurethane with UV- and pH-responsive properties as a novel platform for tumor-targeting drug delivery.
ABSTRACT
Polymeric vesicles constructed from cyclodextrin- and azobenzene-grafted poly(glycidyl methacrylate)s showed excellent stability owing to the multiple host-guest complexation. Upon culturing in Na2S2O4-contained buffer solution, cargo-loaded vesicles disassembled, for potential applications in colon-specific drug delivery.
Subject(s)
Azo Compounds/chemistry , Biocompatible Materials/chemistry , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Drug Delivery Systems , Polymethacrylic Acids/chemistry , beta-Cyclodextrins/chemistry , Biocompatible Materials/chemical synthesis , Cell Line, Tumor , Cell Survival , Humans , Polymethacrylic Acids/chemical synthesisABSTRACT
A series of linear and star-shaped amphiphilic polyethylene glycol block polylactide (PEG-b-PLA) and ß-cyclodextrin (CD) conjugated PEG-b-PLA (PEG-b-PLA-CD) copolymers were synthesized. Bovine serum albumin (BSA) aqueous solution was emulsified in the copolymer organic solutions to fabricate reverse micelles (RMs), and was then further transferred into ethyl oleate (EO), a pharmaceutically acceptable vehicle, by the RMs. As identified by 1H NMR, the RMs were formed with a hydrophilic core of PEG and CD, covered with a hydrophobic corona of PLA moiety, and were spherical in shape, as observed by a scan electronic microscope. Compared with the PEG-b-PLA RMs, the PEG-b-PLA-CD RMs presented higher encapsulation efficiency. The release of BSA was influenced by the copolymer composition and architecture. BSA stability in the release aqueous phase was confirmed by circular dichroism spectroscopy. The oil-based formulation fabricated from biodegradable copolymers with high drug loading showed a great potential for protein delivery.
ABSTRACT
In this feature article, we give an overview of the preparation and application of self-assembled architectures based on an emerging area of polymers, i.e., poly(glycidyl methacrylate)s (PGMAs) and their derivatives. A series of PGMA-based aggregates and hybrids, such as micelles, reverse micelles, capsules, nanoparticles, and inorganic-organic hybrid materials, has been constructed, and diverse morphologies were formed, driven by hydrophobic interactions, hydrogen bonding, ionic complexation, host-guest interactions, etc. In particular, the assemblies have shown great potential applications as drug vectors, gene vectors, solubilizing agents, antimicrobial agent, and so forth. Herein, the general guidelines are elaborately selected from literature examples and partially from our own. Although still in its infancy, self-assembly of PGMA-based polymers is expected to become a hot topic in polymer chemistry and materials science.
