Shenyang Yaoda Pharmaceutical Co. Ltd.

The intratracheal route enables an enhanced drug accumulation within the lungs together with reduced systemic exposure, making it a promising approach for treating epidermal growth factor receptor (EGFR)-overexpressed non-small cell lung cancer (NSCLC). In this study, dextran-PEG-erlotinib co-polymers (DPE), novel amphiphilic conjugates with outstanding therapeutic activities against EGFR-overexpressed NSCLC and stabilizing effects were synthesized and facilitated self-assembly of redox-sensitive paclitaxel dimers. The obtained nanoassemblies (DPE dimer NPs) exhibited high drug loading efficiency, satisfactory stability and optimal redox responsive paclitaxel release profile comparable with control nanoassemblies (TPGS dimer NPs), where paclitaxel dimers were assembled in the presence of TPGS, a therapeutically inert stabilizer. The DPE dimer NPs evidenced an enhanced cellular uptake efficiency and cytotoxicity in EGFR-overexpressed HCC827 cells as compared to TPGS dimer NPs. These also demonstrated superior tumor penetration ability and inhibition potential in HCC827 3D tumor spheroid. Compared to TPGS dimer NPs and Taxol® intravenous injection, the DPE dimer NPs illustrated an improved anticancer effect with reduced systemic toxicity and excellent biocompatibility after intratracheal administration to the HCC827 metastatic lung cancer mouse model. These results revealed a great potential of DPE as a stabilizer to synergistically improve the therapeutic efficacy of paclitaxel dimers against EGFR-overexpressed NSCLC after intratracheal administration.

Bacterial infection contributes to the bioburden of wounds, which is an essential factor in determining whether a wound can heal. Wound dressings with antibacterial properties that can promote wound-healing are highly desired for the treatment of chronic wound infections. Herein, we fabricated a simple polysaccharide-based hydrogel dressing encapsulating tobramycin-loaded gelatine microspheres with good antibacterial activity and biocompatibility. We first synthesised long-chain quaternary ammonium salts (QAS) by the reaction of tertiary amines with epichlorohydrin. The amino groups of carboxymethyl chitosan were then conjugated with QAS through the ring-opening reaction and QAS-modified chitosan (CMCS) was obtained. The antibacterial analysis showed that both QAS and CMCS could kill E. coli and S. aureus at relatively low concentrations. QAS with 16 carbon atoms has a MIC of 16 μg/mL for E. coli and 2 μg/mL for S. aureus. A series of formulations of tobramycin-loaded gelatine microspheres (TOB-G) were generated and the best formulation was selected by comparing the characters of the microspheres. The microsphere fabricated by 0.1 mL GTA was selected as the optimal candidate. We then used CMCS, TOB-G, and sodium alginate (SA) to prepare physically crosslinking hydrogels using CaCl2 and investigated the mechanical properties, antibacterial activity, and biocompatibility of the hydrogels. In summary, the hydrogel dressing we produced can be used as an ideal alternative for the management of bacteria-infected wounds.