title: Antibacterial modification of an injectable, biodegradable, non-cytotoxic block copolymer-based physical gel with body temperature-stimulated sol-gel transition and controlled drug release.
abstract: Biomaterials are being extensively used in various biomedical fields; however, they are readily infected with microorganisms, thus posing a serious threat to the public health care. We herein presented a facile route to the antibacterial modification of an important A-B-A type biomaterial using poly (ethylene glycol) methyl ether (mPEG)- poly(ε-caprolactone) (PCL)-mPEG as a typical model. Inexpensive, commercial bis(2-hydroxyethyl) methylammonium chloride (DMA) was adopted as an antibacterial unit. The effective synthesis of the antibacterial copolymer mPEG-PCL-∼∼∼-PCL-mPEG (where ∼∼∼ denotes the segment with DMA units) was well confirmed by FTIR and (1)H NMR spectra. At an appropriate modification extent, the DMA unit could render the copolymer mPEG-PCL-∼∼∼-PCL-mPEG highly antibacterial, but did not largely alter its fascinating intrinsic properties including the thermosensitivity (e.g., the body temperature-induced sol-gel transition), non-cytotoxicity, and controlled drug release. A detailed study on the sol-gel-sol transition behavior of different copolymers showed that an appropriate extent of modification with DMA retained a sol-gel-sol transition, despite the fact that a too high extent caused a loss of sol-gel-sol transition. The hydrophilic and hydrophobic balance between mPEG and PCL was most likely broken upon a high extent of quaternization due to a large disturbance effect of DMA units at a large quantity (as evidenced by the heavily depressed PCL segment crystallinity), and thus the micelle aggregation mechanism for the gel formation could not work anymore, along with the loss of the thermosensitivity. The work presented here is highly expected to be generalized for synthesis of various block copolymers with immunity to microorganisms. Light may also be shed on understanding the phase transition behavior of various multiblock copolymers.
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Huawen
authors.initials: H
authors.lastname: Hu
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Ka I
authors.initials: KI
authors.lastname: Lee
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Gao
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: He
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Chuilin
authors.initials: C
authors.lastname: Lai
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fei
authors.affiliation: Nanotechnology Center, Institute of Textiles and Clothing, The Hong Kong Polytechnic University, Hong Kong, China. Electronic address: tcxinjh@polyu.edu.hk.
authors.forename: John H
authors.initials: JH
authors.lastname: Xin
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001673:Biodegradation, Environmental; D001831:Body Temperature; D002400:Cathartics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D004642:Emodin / Q000031:analogs & derivatives / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005782:Gels; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008823:Micelles; D044367:Phase Transition; D011091:Polyesters / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D017768:Skin, Artificial; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D044366:Transition Temperature
chemical_list: D000900:Anti-Bacterial Agents; D002400:Cathartics; D003692:Delayed-Action Preparations; D005782:Gels; D008823:Micelles; D011091:Polyesters; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D007770:L-Lactate Dehydrogenase; D004642:Emodin; C006457:alloin
keywords: Amphiphilic balance; Antibacterial modification; Crystallinity; MPEG-PCL-DMA-PCL-mPEG block copolymers; Sol-gel-sol transition