title: Low molecular weight chitosan-coated silver nanoparticles are effective for the treatment of MRSA-infected wounds.
abstract: Silver nanoparticles (AgNPs) are being widely applied as topical wound materials; however, accumulated deposition of silver in the liver, spleen, and other main organs may lead to organ damage and dysfunction. We report here that low molecular weight chitosan-coated silver nanoparticles (LMWC-AgNPs) are effective against methicillin-resistantStaphylococcus aureus(MRSA), have better biocompatibility, and have lower body absorption characteristics when compared with polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nanoparticles without surface stabilizer (uncoated-AgNPs) in a dorsal MRSA wound infection mouse model. LMWC-AgNPs were synthesized by reducing silver nitrate with low molecular weight chitosan as a stabilizer and reducing agent, while PVP-AgNPs were synthesized using polyvinylpyrrolidone as a stabilizer and ethanol as a reducing agent. AgNPs with different surface stabilizers were identified by UV-visible absorption spectrometry, and particle size was determined by transmission electron microscopy. UV-visible absorption spectra of LMWC-AgNPs, PVP-AgNPs and uncoated-AgNPs were similar and their sizes were in the range of 10-30 nm. In vitro experiments showed that the three types of AgNPs had similar MRSA-killing effects, with obvious effect at 4 μg/mL and 100% effect at 8 μg/mL. Bacteriostatic annulus experiments also showed that all the three types of AgNPs had similar antibacterial inhibitory effect at 10 μg/mL. Cell counting kit-8 assay and Hoechst/propidium iodide (PI) staining showed that LMWC-AgNPs were significantly less toxic to human fibroblasts than PVP-AgNPs and uncoated-AgNPs. Treatment of mice with MRSA wound infection demonstrated that the three types of AgNPs effectively controlled MRSA wound infection and promoted wound healing. After continuous application for 14 days, LMWC-AgNPs-treated mice showed significantly reduced liver dysfunction as demonstrated by the reduced alanine aminotransferase and aspartate aminotransferase levels and liver deposition of silver, in comparison to mice treated with uncoated-AgNPs or PVP-AgNPs. Our results demonstrated that LMWC-AgNPs had good anti-MRSA effects, while harboring a better biocompatibility and lowering the body's absorption characteristics.
authors.affiliation: Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chenlu
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qige
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Institute of Traumatic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; Department of Dermatology, Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D012834:Silver / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D013056:Spectrophotometry, Ultraviolet; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D012834:Silver; D048271:Chitosan; D011205:Povidone
keywords: LMWC-AgNPs; MRSA; PVP; PVP-AgNPs; biocompatibility; silver nanoparticles