Han, Sang Duk
(Dong-A ST Research Institute, Pharmaceutical Product Research Laboratories)
,
Sung, Hyun Jung
(Dong-A ST Research Institute, Pharmaceutical Product Research Laboratories)
,
Lee, Ga Hyeon
(Dong-A ST Research Institute, Pharmaceutical Product Research Laboratories)
,
Jun, Joon-Ho
(Dong-A ST Research Institute, Pharmaceutical Product Research Laboratories)
,
Son, Miwon
(Dong-A ST Research Institute, Pharmaceutical Product Research Laboratories)
,
Kang, Myung Joo
(College of Pharmacy, Dankook University)
Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common ...
Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common skin pathogens between the cationic polymer and tyrothricin (TRC), a cyclic polypeptide antibiotic, was investigated, by determining the concentration to inhibit 90% of bacterial isolates (MIC). The addition of the polysaccharide to TRC dramatically reduced the MIC values of TRC by 1/33 and 1/4 against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus, respectively. The synergism of TRC and chitosan combination against both strains was demonstrated by the checkerboard method, with a fractional inhibitory concentration index below 0.5. Moreover, co-treatment of TRC and chitosan exhibited antibacterial activity against Pseudomonas aeruginosa, due to the antibacterial activity of chitosan, whereas TRC itself did not inhibit the gram-negative bacterial growth. These findings suggested that the use of chitosan-based film for topical delivery of TRC could be an alternative to improve TRC antimicrobial activity against strains that are abundant in skin wounds.
Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common skin pathogens between the cationic polymer and tyrothricin (TRC), a cyclic polypeptide antibiotic, was investigated, by determining the concentration to inhibit 90% of bacterial isolates (MIC). The addition of the polysaccharide to TRC dramatically reduced the MIC values of TRC by 1/33 and 1/4 against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus, respectively. The synergism of TRC and chitosan combination against both strains was demonstrated by the checkerboard method, with a fractional inhibitory concentration index below 0.5. Moreover, co-treatment of TRC and chitosan exhibited antibacterial activity against Pseudomonas aeruginosa, due to the antibacterial activity of chitosan, whereas TRC itself did not inhibit the gram-negative bacterial growth. These findings suggested that the use of chitosan-based film for topical delivery of TRC could be an alternative to improve TRC antimicrobial activity against strains that are abundant in skin wounds.
Therefore, the aims of the study were to comparatively evaluate the in vitro antimicrobial activity of the chitosan-based TRC preparation (Dodana gel) and the marketed product (Tyrosur gel) and to investigate the possible synergism between the individual ingredients such as TRC, CPC, and chitosan
대상 데이터
coli (ATCC 25922), and P. aeruginosa (ATCC 27853) were obtained from the American Type Culture Collection (Manassas, VA, USA). ATCC 25923, a clinical isolate with the designation Seattle 1945, has been reported to be susceptible to methicillin and oxacillin [13,14,27].
이론/모형
The MIC values of the marketed products and microbial substances were determined using the microdilution method according to the National Committee of Clinical Laboratory Standards (2004). One gram of each marketed product, namely, Dodana gel (TRC 0.
성능/효과
However, a partially synergistic effect was observed with the chitosan/CPC combination, with MIC values reduced by 1/2 and 1/4 of each compound, respectively. Correspondingly, the combination of chitosan/CPC had a remarkably low FIC value of 0.75, as compared with the TRC/CPC and TRC/chitosan combinations. The partially synergistic effect of the chitosan/CPC combination supports the stronger antiseptic activity of the chitosan-based gel (Dodana gel) against E.
In summary, the primary finding of the study was that the use of chitosan as an external base for topical TRC delivery is advantageous to improve antibacterial activity against common skin pathogens. The combination of TRC with the positively charged polymer was synergistically effective against both MSSA and MRSA, lessening the MIC values of TRC by 1/33 and 1/4, respectively.
On the other hand, co-treatment of TRC with chitosan had a significant effect on enhancing the antibacterial activity of TRC against MRSA. The MIC value of TRC was remarkably reduced to 1/4 in the presence of chitosan (Table 3), suggesting the synergistic effect of TRC and chitosan against the reference strain of MRSA (FIC value of 0.37).
5 μg/ml, as compared with those against gram-positive strains. The TRC/CPC and TRC/chitosan combinations showed no synergistic antimicrobial effects, with a FIC value of over 1.1. However, a partially synergistic effect was observed with the chitosan/CPC combination, with MIC values reduced by 1/2 and 1/4 of each compound, respectively.
In summary, the primary finding of the study was that the use of chitosan as an external base for topical TRC delivery is advantageous to improve antibacterial activity against common skin pathogens. The combination of TRC with the positively charged polymer was synergistically effective against both MSSA and MRSA, lessening the MIC values of TRC by 1/33 and 1/4, respectively. Chitosan also exhibited partially synergistic bactericidal effects with CPC, a preservative, against E.
3 μg/ml). The effect of combination treatment on the viability of MRSA was quite analogous to those obtained from MSSA. The combined treatments of TRC/CPC or chitosan/CPC did not exhibit synergistic effect, with a FIC index of over 1.
were the predominant pathogens in all geographical regions [6]. The stronger microbial activity against these strains was obtained from the treatment of the chitosan-based TRC gel, as compared with the carbomer-based TRC gel in all strains tested, despite the same active ingredients. The MIC values of the chitosan-based TRC gel were only 1/16, 1/2, and 1/4 of those from the Tyrosur gel against MSSA, MRSA, and E.
563 μg/ml for TRC). These results suggested that the incorporation of TRC and/or CPC in the chitosan-based base could eradicate both gram-positive and gram-negative bacteria, by additive and/or synergistic antimicrobial interactions. Several authors proposed a synergistic action of antibiotic and/or preservatives with the cationic polysaccharide.
후속연구
[25] also reported that the combination of sulfamethoxazole and chitosan showed synergistic action against Pseudomonas strains. Based on these findings, we expected that the use of chitosan as an external base for topical delivery of TRC would be beneficial in boosting the antimicrobial activity of TRC and/or CPC, and further investigated these antimicrobial interactions against various strains that are abundant in infected skin.
The formed chitosan film offers barrier function to protect the wound site from the infiltration of microbials, as well as to prevent washout of the antibiotics. Moreover, we expected that the antiseptic effect of the cationic polymer against a broad spectrum of strains abundant in skin and tissues would impart better therapeutic effects with TRC after topical application.
참고문헌 (28)
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