期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 602, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120508
关键词
Multidrug resistance (MDR); Wound infections; Phage therapy; Thermosensitive hydrogel; Poloxamer 407
资金
- Direct Grant for Research Medicine Panel, CUHK [2018.080]
- USydCUHK Partnership Collaboration Awards 2018
The study showed that incorporating phage into hydrogel had minimal impact on bacterial killing efficiency, acting as a phage depot to maintain higher phage titer at the infectious site for more effective treatment. The phage-loaded thermosensitive hydrogel is a simple and promising formulation for managing wound infections, demonstrating significant microbial suppression in ex vivo wound infection models.
With the emergence of multidrug resistance (MDR) bacteria, wound infection continues to be a challenging problem and represents a considerable healthcare burden. This study aims to evaluate the applicability of a phage loaded thermosensitive hydrogel in managing wound infections caused by MDR Acinetobacter baumannii, using IME-AB2 phage and MDR-AB2 as the model phage and bacteria, respectively. Excellent storage stability of the IME-AB2 phage in a -18 wt% Poloxamer 407 (P407) hydrogel solution was first demonstrated with negligible titer loss (-0.5 log) in 24 months at 4 degrees C. The incorporated phage was released in a sustained manner with a cumulative release of 60% in the first 24 h. The in vitro bacterial killing efficiency of phage gel and phage suspension at 37 degrees C demonstrated >5 log(10) CFU/ml reduction against A. baumannii. A comparable biofilm elimination capacity was also noted between the phage gel and phage suspension (59% and 45% respectively). These results suggested that the incorporation of phage into the hydrogel not only had insignificant impacts on the bacterial killing efficiency of phage, but also act as a phage depot to maintain higher phage titer at the infectious site for a prolong period for more effective treatment. We also found that the hydrogel formulation significantly suppressed microbial survival in an ex vivo wound infection model using pig skin (90% reduction in bacterial counts was achieved after 4 h treatment). In summary, our results demonstrated that the P407-based phage-loaded thermosensitive hydrogel is a simple and promising phage formulation for the management of wound infections.
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