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Drug-impregnated polyelectrolyte complex (PEC) sponge composed of chitosan and sodium alginate was prepared for wound dressing application. The morphological structure of this wound dressing was observed to be composed of a dense skin outer layer and a porous cross-section layer by scanning electron microscopy (SEM). Equilibrium water content and release of silver sulfadiazine (AgSD) could be controlled by the number of repeated in situ PEC reactions between chitosan and sodium alginate. The release of AgSD from AgSD-impregnated PEC wound dressing in PBS buffer (PH = 7.4) was dependent on the number of repeated in situ complex formations for the wound dressing. The antibacterial capacity of AgSD-impregnated wound dressing was examined in agar plate against Pseudomonas aeruginosa and Staphylococcus aureus. From the behavior of antimicrobial release and the suppression of bacterial proliferation, it is thought that the PEC wound dressing containing antimicrobial agents could protect the wound surfaces from bacterial invasion and effectively suppress bacterial proliferation. In the cytotoxicity test, cellular damage was reduced by the controlled released of AgSD from the sponge matrix of AgSD-medicated wound dressing. In vivo tests showed that granulation tissue formation and wound contraction for the AgSD plus dihydroepiandrosterone (DHEA) impregnated PEC wound dressing were faster than any other groups.

Sang Joon Lee,1,* Young-Il Jeong,2,* Hyung-Kyu Park,3 Dae Hwan Kang,2,4 Jong-Suk Oh,3 Sam-Gyu Lee,5 Hyun Chul Lee31Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, 2Biomedical Research Institute, Pusan National University Hospital, Busan, 3Department of Microbiology, Chonnam National University Medical School, Gwangju, 4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam, 5Department of Physical and Rehabilitation Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea*These authors contributed equally to this workBackground: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting.Methods: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure.Results: The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity.Conclusion: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.Keywords: cathepsin B, CT26 cell, enzyme-sensitive dendrimer, tumor targeting, tetra peptide