Antimicrobial Properties of a Chitosan Dextran-Based Hydrogel for Surgical Use

ABSTRACT A chitosan dextran-based (CD) hydrogel, developed for use in endoscopic sinus surgery, was tested for antimicrobial activity in vitro against a range of pathogenic microorganisms. The microdilution technique was used to determine minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations. In addition, the time-kill efficacy of CD hydrogel was determined for two bacterial species. Scanning and transmission electron microscopy were carried out to elucidate the antimicrobial mechanism of this compound. CD hydrogel was found to be effective against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Clostridium perfringens at its surgical concentration of 50,000 mg/liter. Minimum bactericidal concentrations ranged from 2,000 to 50,000 mg/liter. Dextran aldehyde (DA) was found to be the antimicrobial component of the CD hydrogel with MBC ranging from 2,000 to 32,000 mg/liter. S. aureus appeared to be killed at a slightly faster rate than E. coli. Candida albicans and Pseudomonas aeruginosa were more resistant to CD hydrogel and DA. Scanning and transmission electron microscopy of E. coli and S. aureus incubated with CD hydrogel and DA alone revealed morphological damage, disrupted cell walls, and loss of cytosolic contents, compatible with the proposed mode of action involving binding to cell wall proteins and disruption of peptide bonds. Motility and chemotaxis tests showed E. coli to be inhibited when incubated with DA. The antibacterial activity of CD hydrogel may make it a useful postsurgical aid at other body sites, especially where there is a risk of Gram-positive infections.

[1]  G. Sarwar,et al.  Antiseptics and Disinfectants: Activity, Action, and Resistance , 2013 .

[2]  A. Beule,et al.  Effects of a Novel Chitosan Gel on Mucosal Wound Healing Following Endoscopic Sinus Surgery in a Sheep Model of Chronic Rhinosinusitis , 2008, The Laryngoscope.

[3]  U. Pennsylvania,et al.  Clinical and Laboratory Standards Institute , 2019, Springer Reference Medizin.

[4]  P. Lambert,et al.  Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. , 2002, Journal of the Royal Society of Medicine.

[5]  M. Canuto,et al.  Antifungal drug resistance to azoles and polyenes. , 2002 .

[6]  Robert Langer,et al.  Synthesis and Characterization of in Situ Cross-Linkable Hyaluronic Acid-Based Hydrogels with Potential Application for Vocal Fold Regeneration , 2004 .

[7]  S. Hudson,et al.  Synthesis and antimicrobial activity of a water-soluble chitosan derivative with a fiber-reactive group. , 2004, Carbohydrate research.

[8]  Ming Kong,et al.  Antimicrobial properties of chitosan and mode of action: a state of the art review. , 2010, International journal of food microbiology.

[9]  Tony M. Kuriger,et al.  Synthesis and Characterization of Chitosan/ Dextran‐Based Hydrogels for Surgical Use , 2009 .

[10]  E. Khor Chitin: a biomaterial in waiting , 2002 .

[11]  A. Van de Voorde,et al.  In vitro release characteristics of bioactive molecules from dextran dialdehyde cross-linked gelatin hydrogel films. , 1998, Biomaterials.

[12]  N. Artzi,et al.  Aldehyde‐Amine Chemistry Enables Modulated Biosealants with Tissue‐Specific Adhesion , 2009, Advanced materials.

[13]  J. Maillard,et al.  A NOTE: Ortho‐Phthalaldehyde: proposed mechanism of action of a new antimicrobial agent , 2000, Letters in applied microbiology.

[14]  S. Moratti,et al.  The Efficacy of a Novel Chitosan Gel on Hemostasis and Wound Healing after Endoscopic Sinus Surgery , 2010, American journal of rhinology & allergy.

[15]  R. Almeida,et al.  Novel Single-Tube Agar-Based Test System for Motility Enhancement and Immunocapture of Escherichia coli O157:H7 by H7 Flagellar Antigen-Specific Antibodies , 2002, Journal of Clinical Microbiology.

[16]  Moon-Moo Kim,et al.  Applications of Chitin and Its Derivatives in Biological Medicine , 2010, International journal of molecular sciences.

[17]  A. Abad Medium temperature epoxy resin for immunocytochemistry: Quetol 651 with water , 1992, Microscopy research and technique.

[18]  P. Wormald,et al.  Impaired Mucosal Healing and Infection Associated with Staphylococcus Aureus After Endoscopic Sinus Surgery , 2009, American journal of rhinology & allergy.

[19]  E. Kot,et al.  Novel water-soluble photosensitizers from dextrans. , 2004, Biomacromolecules.

[20]  A. D. Russell,et al.  Antiseptics and Disinfectants: Activity, Action, and Resistance , 2001, Clinical Microbiology Reviews.

[21]  M. Ferraro Performance standards for antimicrobial susceptibility testing , 2001 .

[22]  J. Andrews,et al.  Determination of minimum inhibitory concentrations. , 2001, The Journal of antimicrobial chemotherapy.

[23]  D. Sanglard,et al.  Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation. , 2009, FEMS yeast research.

[24]  Sheng Yang,et al.  Chitosan kills Escherichia coli through damage to be of cell membrane mechanism , 2010 .

[25]  C. Penn,et al.  Bacterial flagellar diversity and significance in pathogenesis. , 1992, FEMS microbiology letters.

[26]  N. Heindel,et al.  Determination of Degree of Substitution of Formyl Groups in Polyaldehyde Dextran by the Hydroxylamine Hydrochloride Method , 1991, Pharmaceutical Research.

[27]  M. Masiá Canuto,et al.  Antifungal drug resistance to azoles and polyenes. , 2002, The Lancet. Infectious diseases.