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1.
Macromol Biosci ; 16(4): 591-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26756211

ABSTRACT

Polymicrobial biofilm-associated implant infections present a challenging clinical problem. Through modifications of lyophilized chitosan sponges, degradable drug delivery devices for antibiotic solution have been fabricated for prevention and treatment of contaminated musculoskeletal wounds. Elution of amikacin, vancomycin, or a combination of both follows a burst release pattern with vancomycin released above minimum inhibitory concentration for Staphylococcus aureus for 72 h and amikacin released above inhibitory concentrations for Pseudomonas aeruginosa for 3 h. Delivery of a vancomycin, amikacin, or a combination of both reduces biofilm formation on polytetrafluoroethylene catheters in an in vivo model of contamination. Release of dual antibiotics from sponges is more effective at preventing biofilm formation than single-loaded chitosan sponges. Treatment of pre-formed biofilm with high-dose antibiotic release from chitosan sponges shows minimal reduction after 48 h. These results demonstrate infection-preventive efficacy for antibiotic-loaded sponges, as well as the need for modifications in the development of advanced materials to enhance treatment efficacy in removing established biofilm.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Catheter-Related Infections/drug therapy , Chitosan/chemistry , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Acetates/chemistry , Amikacin/chemistry , Amikacin/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Biofilms/growth & development , Catheter-Related Infections/microbiology , Catheters/microbiology , Delayed-Action Preparations , Disease Models, Animal , Drug Compounding , Drug Liberation , Freeze Drying , Humans , Mice , Polytetrafluoroethylene , Pseudomonas aeruginosa/physiology , Skin , Staphylococcus aureus/physiology , Vancomycin/chemistry , Vancomycin/pharmacology
2.
J Biomed Mater Res B Appl Biomater ; 103(2): 387-96, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24895066

ABSTRACT

Chitosan sponges were developed for adjunctive local antibiotic delivery to reduce bacteria in wounds. There is a need to increase sponge degradation for rapid clearance from the wound site during initial wound care. This work examined the effect of using 0.25 M sodium acetate buffers, at pH 4.6 or 5.6, to fabricate sponges with an amorphous chitosan polymer structure. Sponges were evaluated for their crystallinity, thermal, spectroscopic, and morphological properties, in addition to in vitro degradation, and cytocompatibility analysis using normal human dermal fibroblasts. In vivo degradation and biocompatibility were also examined after 4 and 10 days in rat intramuscular tissues. Both buffered chitosan sponge variations exhibited decreases in crystallinity and thermal decomposition temperatures, and increases in surface roughness, which resulted in over 40% increases in degradation over 10 days in vitro compared to the neutral sponges. There were no significant differences between sponges during in vivo degradation over 10 days with respect to histomorphometric analysis of the recovered sponges. These results demonstrated that the acetate buffer did change characteristic chitosan sponge material properties, and increasing the in vivo sponge degradation rate will require balancing material characteristics and processing.


Subject(s)
Absorbable Implants , Anti-Bacterial Agents , Biocompatible Materials , Chitosan , Drug Implants , Muscle, Skeletal , Wound Infection/therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacokinetics , Buffers , Cell Line , Chitosan/chemistry , Chitosan/pharmacology , Drug Implants/chemistry , Drug Implants/pharmacology , Humans , Male , Rats , Rats, Sprague-Dawley , Sodium Acetate/chemistry
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