Introduction
Silver nanoparticles (AgNPs) are being widely applied as topical wound materials; however, accumulated amounts of silver in the liver, spleen, and other main organs may lead to organ damage and dysfunction.
Researchers (from the Department of Dermatology, Wellman Center for Photomedicine – Harvard Medical School, and Department of Burns and Plastic Surgery, Shanghai Ninth People’s Hospital – Shanghai Jiao Tong University School of Medicine) pursued a possible solution with combining AgNPs with polymer systems.
The researchers exaimined low molecular weight chitosan-coated silver nanoparticles (LMWC-AgNPs) compared to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nanoparticles without surface stabilizer (uncoated-AgNPs) in a dorsal MRSA wound infection mouse model. They found that LMWC-AgNPs demonstrated;
- More effectiveness against methicillin-resistant Staphylococcus aureus (MRSA)
- Better biocompatibility
- Lower absorption into the body and organs
Yinbo Peng et al, synthesized LMWC-AgNPs by nanoparticlizing silver nitrate and 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.
The in vitro experiments found that the 3 types of AgNPs had similar MRSA bactericidal effects at 4 μg/mL and 100% effective at 8 μg/mL. A bacteriostatic annulus analysis also showed that all 3 types of AgNPs had similar antibacterial inhibitory effect at 10 μg/mL. But, LMWC-AgNPs demonstrated significantly less toxicity to human fibroblasts than PVP-AgNPs and uncoated-AgNPs.
In vivo experiments found that treatment of mice with MRSA wound infection, all 3 types of AgNPs effectively controlled MRSA wound infection and promoted wound healing. But following continuous application for 14 days, LMWC-AgNPs-treated mice demonstrated significantly reduced liver dysfunction as demonstrated by the reduced alanine aminotransferase and aspartate aminotransferase levels and liver deposition of silver compared to mice treated with uncoated-AgNPs and PVP-AgNPs.
Results
Due to their antibacterial properties, AgNPs are widely used in various types of medical materials, such as topical trauma therapeutics.4,17,18 This is partially due to, when compared to silver ions, they have demonstrated much lower levels of cytotoxicity. Despite this, AgNPs still induce cell damage through induction of apoptosis.19–21 This can be influenced by the AgNPs’ particle size, pH, surface-stabilizing agents, pH, etc.1,5,7,22–24 Whereas, the latter has been also cited as an most important factor in the protection of cell viability.25–27
The literature states that chitosan and chitosan/AgNPs materials possesses robust biocompatibility capabilities, antibacterial properties, could promote wound healing.3,17,28–30 In comparison with long-chain high molecular weight chitosan, short-chain LMWC is favorable with regard to its water solubility and biocompatibility. With this, its been established that LMWC:
- Enhances the physical and chemical stability of many drugs such as, insulin31 and siRNA,32
- Functions as a suitable carrier for the delivery and controlled release of drugs.
Technical Take-Aways
- Low molecular weight chitosan (2,000 and 2,500 Da) is soluble in water and better biological activity vs. high molecular weight chitosan.
- Low molecular weight chitosan (LMWC) was used as a stabilizer and a reducing agent for direct synthesis of LMWC-Silver nanoparticles (LMWC-AgNPs) with particle diameter size of 10–30 nm.
- Surface coating with LMWC-AgNPs reduces cell toxicity and increases cell viability.
- LMWC-AgNPs demonstrates anti-MRSA infection, low cytotoxicity, better biocompatibility, and less risk of liver function damage both in vitro and in vivo experiments vs. comparator and control.
Conclusion
LMWC-AgNPs, when compared with PVP-AgNP and uncoated-AgNP treatments in vitro and in vivo experiments, demonstrates:
- Better anti-bacterial effects against MSRA
- Less body and organ absorption of silver
- Lower cytotoxicity
- Better biocompatibility
Low molecular weight chitosan-silver nanoparticles may be a safer and more effective for medical applications which presents in for patients with large-area burns and wounds and with need for antibacterial effects against methicillin-resistant Staphylococcus aureus.
