Teicoplanin-loaded chitosan-PEO nanofibers for local antibiotic delivery and wound healing.

Antibiotic-loaded nano-delivery systems offer an advanced approach to overcome several limitations associated with antibiotic therapy. Antibiotic-loaded nanofibers can be applied topically for skin and wound healing, post operation implants for the prevention of abdominal adhesion, and prophylaxis and treatment of infections in orthopedic surgery. Here, the authors report the development of local antibiotic delivery system using chitosan- polyethylene oxide (PEO) nanofibers for delivery of teicoplanin. Successful electrospinning of chitosan-PEO solution containing 2 and 4 w/v% teicoplanin resulted in uniform and bead-less nanofibers. Nanofibers were able to release teicoplanin up to 12 days. Antibacterial test in agar diffusion and time-kill study on Staphylococcus aureus also demonstrate that loading teicoplanin in chitosan-PEO nanofibers not only kept the antibacterial activity of antibiotic but also, enhanced it up to 1.5 to 2 fold. Teicoplanin loaded nanofibers did not show any cytotoxicity to human fibroblast. Moreover, in vivo study on rat full thickness wound model confirmed safety and efficacy of applying teicoplanin loaded nanofibers and significant improve in wound closure was observed especially with nanofibers containing 4% teicoplanin. The sustained release profile, enhanced drug activity, cytocompatibility, and significant wound healing activity affirm the potential applications of teicoplanin-loaded nanofibers in wound healing and local antibiotic delivery.

Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor.

Leptin is an appetite regulatory hormone that is secreted into the blood circulation by the adipose tissue and it functions via its over expressed receptors (Ob-R) in a wide variety of cancers. In the present study, the function of a leptin-derived peptide (LP16, 91-110 of Leptin) was investigated as a targeting ligand to decorate PEGylated liposomal doxorubicin (PLD, Doxil®) surface and the anti-tumor activity and therapeutic efficacy of Doxil in C26 (Colon Carcinoma) tumor model were also evaluated. As a result of this, Doxil with different LP16 peptide density (25, 50, 100 and 200 peptide on the surface of each liposome) was successfully prepared and characterized. In vitro results showed significant enhanced cytotoxicity and cellular binding and uptake of LP16-targeted Doxil formulations (LP16-Doxil) in C26 cells as compared to Doxil. In BALB/c mice bearing C26 murine carcinoma, at a dose of 15 mg/kg, LP16-Doxil groups (100 ligand) significantly suppressed the growth of the tumor and showed higher inclination to tumor as compared to non-targeted Doxil. This study revealed that the potential of LP16 peptide targeting increased the therapeutic efficacy of Doxil and highlighted the importance of optimizing the ligand density to maximize the targeting ability of the nanocarriers and merits further investigations.