Chitosan-polyvinyl alcohol nanoscale liquid film-forming system facilitates MRSA-infected wound healing by enhancing antibacterial and antibiofilm properties

International Journal of Nanomedicine Dovepress open access to scientific and medical research O r i g in a l R e s e a r c h International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 54.37.163.172 on 21-Dec-2018 For personal use only. Open Access Full Text Article Chitosan-polyvinyl alcohol nanoscale liquid filmforming system facilitates MRSA-infected wound healing by enhancing antibacterial and antibiofilm properties This article was published in the following Dove Press journal: International Journal of Nanomedicine Sha Yang* Yun Yang* Sixin Cui Ziqi Feng Yuzhi Du Zhen Song Yanan Tong Liuyang Yang Zelin Wang Hao Zeng Quanming Zou Hongwu Sun National Engineering Research Center of Immunological Products & Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA, Chongqing, 400038, People’s Republic of China *These authors contributed equally to this work Correspondence: Quanming Zou; Hongwu Sun National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA, 30 Sha Ping Ba Gaotanyan Street, Chongqing, 400038, People’s Republic of China Tel/fax +86 23 6875 2377 Email ; Introduction Wound healing has always been an important topic in medicine and biology, and thus, an area of interest for many years.1 Once a wound occurs, the normal function of the skin is disrupted due to the incomplete anatomical structure and natural defense barriers, and microorganisms can thereupon easily invade and infect the wound site.2 This issue has become a major public health care burden accounting for more than 25 billion dollars in costs annually.3 Wound healing is crucial for restoring the functional status and anatomical continuity of skin tissue.2 Delayed healing is the most challenging problem in wound management, and bacterial contamination is a major obstacle to the wound-healing process.4 Many antimicrobial agents are available, including silver sulfadiazine, polymyxin B sulfate, gentamycin, neomycin, and bacitracin, and these agents are widely applied to treat wound infections. However, when applied in common topical forms, such as ointments and gels, these agents barely perform in practical applications because they are easily wiped from wound exposure sites.5 Thus, a novel suitable formulation for wounds is vital. Methicillin-resistant Staphylococcus aureus (MRSA) is of particular concern because of the limited treatment measures available for treating MRSA wound 4987 submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2018:13 4987–5002 Dovepress © 2018 Yang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IJN.S161680 Powered by TCPDF (www.tcpdf.org) Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most predominant and fatal pathogens at wound infection sites. MRSA is difficult to treat because of its antibiotic resistance and ability to form biofilms at the wound site. Methods: In this study, a novel nanoscale liquid film-forming system (LFFS) loaded with benzalkonium bromide was produced based on polyvinyl alcohol and chitosan. Results: This LFFS showed a faster and more potent effect against MRSA252 than benzalkonium bromide aqueous solution both in vitro and in vivo. Additionally, the LFFS had a stronger ability to destroy biofilms (5 mg/mL) and inhibit their formation (1.33 μg/mL). The LFFS inflicted obvious damage to the structure and integrity of MRSA cell membranes and caused increases in the release of alkaline phosphate and lactate dehydrogenase in the relative electrical conductivity and in K+ and Mg2+ concentrations due to changes in the MRSA cell membrane permeability. Conclusion: The novel LFFS is promising as an effective system for disinfectant delivery and for application in the treatment of MRSA wound infections. Keywords: liquid film-forming system, methicillin-resistant Staphylococcus aureus, wound healing, antibiofilm, antibacterial Dovepress International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 54.37.163.172 on 21-Dec-2018 For personal use only. Yang et al infections.6 MRSA has become a leading cause of wound infection and is not easily eradicated by routine antimicrobial therapies, making MRSA outbreaks a worldwide problem in recent decades, especially in the developing world. Moreover, biofilms, which are commonly present at wound infection sites, formed by MRSA can delay wound healing and resist the therapeutic efficacy of conventional antibiotics.7 Therefore, a novel and effective therapy to treat MRSA wound infections is urgently needed. Benzalkonium bromide (BZL), a well-known quaternary ammonium compound, is a common cationic surfactant widely utilized in industrial and medical applications, including as a sanitizer, a fungicide, an antiseptic, a disinfectant, and an emulsifier.8 Our previous studies have shown that BZL can effectively inhibit MRSA, and the compound is currently in the form of a foam, a sponge, and a hydrogel to optimize its pharmaceutical properties in topical administration. However, the drug retention times of the above formulations at the wound site are too short to play an efficient role in MRSA eradication.9 Therefore, a suitable delivery system containing BZL for wound healing is necessary in clinical applications. Liquid film-forming systems (LFFSs) are ideal for this situation because of the following advantages: enhanced therapeutic efficacy and wound-healing activity, reduced side effects, and minimized administration frequency. 9 Polyvinyl alcohol (PVA) is widely used in film preparation for its excellent biodegradable properties and low toxicity.10 PVA 0588 is the only PVA derivative that has been approved &+ &+ &+ &+ 1 %U± by the China Food and Drug Administration for biomedical applications and is attracting increasing attention due to its optimal biocompatibility and unique mechanical properties.11 Studies have shown that biomimetic material, chitosan (CS), loaded with antibiotics can prolong drug residence time and prevent injury, thereby lessening infections in wound tissues. Furthermore, films made of CS have been used extensively in drug delivery systems and tissue engineering scaffold (...truncated)