Table 1.
Chitosan-based delivery systems and scaffolds in biofilm eradication for localized antimicrobial therapy. The MW and DDA denoted for each study.
| Delivery System/Scaffold |
System | Microorganisms | Findings | Ref. |
|---|---|---|---|---|
| MW | ||||
| DDA | ||||
| Particles and carriers | CNPs: Chitosan 107 kDa DDA: 75–85% |
S. aureus MRSA MRSE |
In vitro antibiofilm activity: The CNPs were able to inhibit biofilm formation in all strains, however, only by around 30% for MRSE, while S. aureus and MRSA had inhibitions of more than 90% and approximately 75%, respectively. |
[151] |
| CNPs: Chitosan 1.6 kDa DDA: 92% Rhamnolipid |
S. aureus
S. epidermidis Klebsiella oxytoca |
In vitro antibiofilm activity: CNPs with the surface-active compound rhamnolipid demonstrated superior antibiofilm activity against S. aureus and S. epidermidis; however, the antibiofilm action in the Gram-negative bacteria K. oxytoca was absent. |
[152] | |
| Excipient and coatings | Chitosan-coated NPs or CNPs incorporated into microneedles: Chitosan 50–190 kDa DDA: n.a. Doxycycline |
S. aureus
P. aeruginosa |
In vitro antibiofilm activity: The bacterial eradication of doxycycline-loaded NPs with chitosan was superior to the free drug in all strains. More than 99% of the bacterial biofilm was eradicated at 4× MIC. Ex vivo porcine antibiofilm activity: the chitosan-coated NPs incorporated in microneedles eradicated upwards of 97% of the bacteria in all strains. |
[153] |
| Lipid-polymer hybrid nanovesicles: Chitosan ≈250 kDa DDA: 75–85% Vancomycin |
MRSA | In vitro antibiofilm activity: The lipid-polymer hybrid nanovesicles with vancomycin demonstrated superior eradication of MRSA biofilm. |
[154] | |
| Microneedles: Chitosan MW: n.a. DDA: n.a. Zinc |
E. coli
S. aureus |
In vitro antibiofilm activity: The zinc-loaded microneedles displayed superior antibiofilm activity in a concentration-dependent manner. In the highest zinc concentrations, almost all bacteria were killed. The unloaded microneedles killed more bacteria than the control but were less effective than the zinc-loaded microneedles. |
[155,156] | |
| Hydrogel: Chitosan LMW DDA: n.a. Methylene blue |
Propionibacterium acnes | In vitro antibiofilm activity: The chitosan/poloxamer hydrogel displayed moderate but significant antibiofilm activity; however, no additional antibiofilm effects from methylene blue were observed. |
[157] | |
| Composite matrix: Chitosan 50–190 kDa DDA: ≥85% Silver NPs |
C. albicans | In vitro antibiofilm activity: Compared to the control, the chitosan matrix with silver NPs and silver NPs alone reduced the number of viable cells in both C. albicans strains. |
[158] | |
| Film: Chitosan 120 kDa DDA: n.a. Ciprofloxacin |
S. aureus
P. aeruginosa |
In vitro antibiofilm activity: The ciprofloxacin-loaded films comprising chitosan and bacterial cellulose eradicated bacteria within 1 h of treatment. Inhibition towards both strains; however, stronger in P. aeruginosa |
[159] | |
| Polymer-based gels | Hydrogel: Chitosan 25–35 kDa DDA: >90% Toluidine blue O |
S. aureus
P. aeruginosa |
In vitro antibiofilm activity: The hydrogels comprising chitosan and HPMC with toluidine blue O displayed good anti-biofilm activity in biofilms produced by S. aureus or P. aeruginosa with 1- to 3-log bacterial killing and proper biofilm penetration. |
[160] |
| Hydrogel: Chitosan 320 kDa DDA: n.a. Antimicrobial peptides: (ASP)-1 ASP-2 |
P. aeruginosa A. baumannii MRSA |
In vitro antibiofilm activity: The peptide-loaded hydrogels had strong anti-biofilm activity in P. aeruginosa and MRSA, especially in P. aeruginosa, where the formulation was superior to a commercialized silver product. Ex vivo porcine antibiofilm activity: The peptide-loaded hydrogels surpassed the commercial product in all three strains and exhibited a strong eradication of the biofilms. |
[161] | |
| Hydrogel: Chitosan LMW DDA: 95.6% ε-poly-L-lysine |
MDR- P. aeruginosa MRSA C. albicans |
Ex vivo antibiofilm activity: The ε-poly-l-lysine loaded hydrogels reduced the thickness of the polymicrobial biofilm and reduced the bacterial load of P. aeruginosa; however, the bacterial burden of the other organisms was not reduced. |
[162] | |
| Hydrogel: Chitosan 190–375 kDa DDA: n.a. Silver NPs |
P. aeruginosa MRSA |
Polymicrobial biofilm activity: The silver NP-loaded chitosan hydrogel significantly reduced the bacterial load of MRSA in all concentrations of the nanoparticles. The bacterial load of P. aeruginosa was also reduced; however, the reduction was lower than for MRSA, and higher NP concentrations were required. |
[163] | |
| Hydrogel: Succinyl chitosan 200 kDa DDA: 87% Cellobiose dehydrogenase Cellulase from Trichoderma longibrachiatum |
S. aureus
E. coli |
In vitro antibiofilm activity: The unloaded hydrogel demonstrated anti-biofilm activity against both S. aureus and E. coli. The enzyme-loaded hydrogel had approximately the same level of inhibition. |
[164] | |
| Scaffolds | Matrix: Chitosan 200 kDa or 350 kDa DDA: n.a. Papain |
S. aureus
S. epidermidis |
In vitro antibiofilm activity: Slightly improved activity from MMW chitosan with papain compared to HMW chitosan. |
[165] |
| Membrane: Chitosan 311.5 kDa DDA: 71% Cis-2-decenoic acid Bupivacaine |
MRSA | In vitro antibiofilm activity: Almost all membranes displayed significant antibiofilm effects both upon evaluating the growth on the dressings and in wells. |
[166] |
The n.a. refers to not applicable/not denoted; CNP: chitosan nanoparticles, DDA: degree of deacetylation, HMW: high molecular weight, LMW: low molecular weight, MDR: multi-drug-resistant MIC: minimum inhibitory concentration, MMW: medium molecular weight, HPMC: hydroxypropyl methylcellulose, MRSA: methicillin-resistant S. aureus, MRSE: Methicillin-resistant S. epidermidis, MW: molecular weight, NPs: nanoparticles.