Collagen-based wound dressing for doxycycline delivery: in-vivo evaluation in an infected excisional wound model in rats.
OBJECTIVE
A novel collagen-based dressing consisting of 2,3-dihydroxybenzoic-acid-modified gelatin microspheres loaded with doxycycline has previously been reported to address both infection and matrix degradation. In the present study the potential benefits of the dressing were investigated in an excisional wound model in rats challenged with Pseudomonas aeruginosa.


METHODS
A full-thick excisional wound (1.5 x 1.5 cm) was created on the dorsum of the rats and infection induced by injecting 10(5) colony-forming units (CFU) of P. aeruginosa. The healing pattern was assessed from wound reduction, matrix metalloprotease (MMP) levels, CFU reduction and histological and biochemical analysis.


RESULTS
The treated group exhibited complete healing by day 15, compared with day 24 in the control group. Early subsidence of infection (99.9% by day 9) resulted in faster epidermal resurfacing and fibroplasias, whereas the microbial load exceeded 10(3) CFU even on day 15 in the control group and caused severe inflammation. Biochemical analysis showed that the expression of both collagen and hexosamine was significantly increased in the treated group. Gelatin zymography revealed prolonged expression of MMPs 2, 8 and 9 in the control group compared with the treated group.


CONCLUSIONS
The study indicates that the developed dressing attenuated both infection and metalloprotease levels, and may therefore have potential application in wound healing.
Adhirajan
Natarajan
N
Biomaterials Division, Central Leather Research Institute, Chennai, India.
Shanmugasundaram
Natesan
N
Shanmuganathan
Seetharaman
S
Babu
Mary
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047070:Bandages, Hydrocolloid; D003094:Collagen / Q000378:metabolism; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005782:Gels; D006595:Hexosamines / Q000378:metabolism; D062385:Hydroxybenzoates; D007249:Inflammation / Q000517:prevention & control; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D008863:Microspheres; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D005782:Gels; D006595:Hexosamines; D062385:Hydroxybenzoates; C009135:2,3-dihydroxybenzoic acid; D003094:Collagen; D053505:Matrix Metalloproteinases, Secreted; D004318:Doxycycline