ABSTRACT
To enhance the chemotherapy effect to MDA-MB-231, a glutathione (GSH)-sensitive amphiphilic hyperbranched poly (amide-amine) (mPEG-PLGA-HPAA) was synthesized, and the anti-cancer drug, paclitaxel (PTX) was then encapsulated into the mPEG-PLGA-HPAA micelles. The mPEG-PLGA-HPAA containing a large number of disulfide bonds could degrade and then consume the GSH intracellularly, which was expected to enhances the sensitivity of MDA-MB-231 cells to PTX. It was found that the mPEG-PLGA-HPAA/PTX nanoparticles could respond to the GSH and showed a GSH-controlled PTX release. Simultaneously, the mPEG-PLGA-HPAA/PTX nanoparticles significantly enhanced the efficacy of PTX by inhibiting MDA-MB-231 cells proliferation and inducing cells apoptosis, performing the self-sensitization effect of chemotherapy. Moreover, the drug carrier of mPEG-PLGA-HPAA exhibited excellent biocompatibility in vitro and in vivo. These results indicated that the self-sensitized drug carrier is a promising route to maximize the therapeutic effect and minimize the side effects of chemotherapy drugs used currently in clinical.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drug Delivery Systems , Paclitaxel/pharmacology , Polyamines/chemistry , Polyesters/chemistry , Polyethylene Glycols/chemistry , Surface-Active Agents/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , HEK293 Cells , Humans , Molecular Structure , Paclitaxel/chemistry , Particle Size , Polyamines/chemical synthesis , Polyesters/chemical synthesis , Polyethylene Glycols/chemical synthesis , Surface Properties , Surface-Active Agents/chemical synthesisABSTRACT
As a promising drug carrier, graphene oxide (GO) has been studied widely in drug delivery due to its excellent loading ability to aromatic drugs. However, its biocompatibility, such as stability and blood compatibility, is now the biggest obstacle for its further application. Herein, the hyperbranched polyglycerol (HPG)-modified GO was prepared through the anionic ring-opening polymerization using GO as the initiator directly, and then the doxorubicin hydrochloride was loaded and showed obvious cytotoxicity to tumor cells. The obtained HPG-GO displayed good stability in the aqueous solution, as well showed low toxicity in vitro and in vivo. As an injectable drug carrier, HPG-GO showed good blood compatibility with negligible effect on the hemolysis and blood coagulation. Such a stable and blood-compatible GO derivative may be applied widely in drug delivery in the future.
Subject(s)
Glycerol/chemistry , Polymers/chemistry , Drug Carriers , Graphite , OxidesSubject(s)
Hydrogels , Triclosan , Ultraviolet Rays , 3T3 Cells , Animals , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Hydrogels/chemical synthesis , Hydrogels/chemistry , Hydrogels/pharmacokinetics , Hydrogels/pharmacology , Mice , Triclosan/chemistry , Triclosan/pharmacokinetics , Triclosan/pharmacologyABSTRACT
To encapsulate the hydrophobic camptothecin (CPT) into hydrogel matrix with a high loading amount, a supramolecular hydrogel hybrided with multi-walled carbon nanotubes (MWNTs) was developed by the host-guest interactions and used for loading and delivering CPT. Firstly, carboxylated MWNTs were modified by polyethylene glycol monomethyl ether (MPEG), which resulted in the water-dispersed MPEG-MWNTs. Then α-cyclodextrin (α-CD) was mixed with MPEG-MWNTs and the hybrid supramolecular hydrogel was fabricated by the inclusion interactions between α-CD and MPEG. The used MPEG not only dispersed MWNTs in aqueous solution, but also functioned as hydrogel matrix by interacting with α-CD. The gelation time for the sol-gel transition and rheological properties of the resultant hydrogels were studied. Due to the excellent application of MWNTs in drug delivery, hydrophobic CPT could be loaded into the hydrogel matrix by a higher amount compared with micelles. By in vitro release and cell viability tests, it was found that the encapsulated CPT could exhibit a controlled and sustained release behavior as well as sustained antitumor efficacy.
