ABSTRACT
Polyurethane micelles with disulfide linkage located at the interface of hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug release profiles. However, the payloads could not be released completely. The occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG coronas was considered as the reason for the incomplete release. To verify the above hypothesis and to develop a new polyurethane based micelles with dual stimuli respond properties and controllable location of pH and reduction responsive groups in the PU main chains, a tertiary amine was incorporated into the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide linkages located between the hydrophilic PEG segment and the hydrophobic PCL segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen as mode hydrophobic drug to evaluate the loading and redox triggered release profiles of the PU micelles. It was demonstrated that PU-SS-N micelles disassembled instantly at the presence of 10mM GSH and at an acidic environment (pH=5.5), which resulted the nearly complete release (~90%) of the payloads within 48h, while about ~70% PTX was released from PU-SS-I and PU-SS-N micelles at neutral environment (pH=7.4) with the presence of 10mM GSH. The rapid and complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will be a promising anticancer drug delivery system to ensure sufficient drug concentration to kill the cancer cells and to prevent the emergency of MDR. The in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also assessed in H460 and HepG2 cells.
Subject(s)
Drug Delivery Systems/methods , Micelles , Paclitaxel , Polyurethanes , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Hep G2 Cells , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Humans , Hydrogen-Ion Concentration , Oxidation-Reduction , Paclitaxel/chemistry , Paclitaxel/pharmacokinetics , Paclitaxel/pharmacology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/pharmacology , Polyurethanes/chemistry , Polyurethanes/pharmacokinetics , Polyurethanes/pharmacologyABSTRACT
Inspired by mussel-adhesion phenomena in nature, a simple, mild surface modification process was elaborated to endow the polyurethane (PU) substrate with antibacterial/antifouling properties. In the present study, polydopamine was coated directly onto polyurethane surfaces. AgNO3 was then added and absorbed onto the surface by the active catechol and amine groups of the polydopamine coating. Meanwhile, the adsorbed Ag+ ions were reduced in situ into metallic silver nanoparticles by the "bridge" of the polydopamine coating which yielded a coating with good antimicrobial properties. Finally, 1H, 1H, 2H, 2H-perfluorodecanethiol (CF3 (CF2 )7 CH2 CH2 SH, F-SH) was attached on the PDA coating via the Michael addition reaction. The hydrophobic F-SH layer above the antibacterial layer yielded a surface with excellent antifouling properties. Preliminary antibacterial assays indicate that the coated surfaces show enhanced antibacterial activity against Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). Platelet adhesion was significantly reduced for the F-SH-coated PU film. These results suggest that the modified PU could be used as an antibacterial material for future biomedical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 531-538, 2017.
