A novel and easy to prepare azo-based bioreductive linker and its application in hypoxia-sensitive cationic liposomal doxorubicin: Synthesis, characterization, in vitro and in vivo studies in mice bearing C26 tumor.

This study designed and synthesized a cost-effective azo-based hypoxia-sensitive linker (AHSL) using commercially accessible, inexpensive raw materials and simple methods to apply in cationic nanoliposomes. Then, AHSL was post-inserted into the cationic liposome (Cat-lip), and PEG-Azo-Cat-lip was prepared and characterized using DLS. The decrease in the zeta-potential of formulation from + 18.4 mV for Cat-lip to + 6.1 mV and the increase in the size of the PEG-Azo-Cat-lip indicated the successful post insertion of AHSL into the liposomes. The Doxorubicin (Dox) release study showed that PEGylation results in a more stable PEG-Azo-Cat-lip than the Cat-lip. The increased cytotoxicity of the PEG-Azo-Cat-lip in the hypoxic condition also indicated the cleavage of the AHSL in the hypoxic environment. In vivo biodistribution using animal imaging has shown higher tumor accumulation of the MPEG-Azo-Cat-lip than Cat-lip during the 120 h of the study. The results of anti-tumor activities and biosafety of the formulations also showed the higher efficiency of the MPEG-Azo-Cat-lip compared with the Cat-lip. The results of this study indicated the antitumor efficacy of this hypoxia-sensitive which merits further investigation.

Bacterial biofilms and their resistance mechanisms: a brief look at treatment with natural agents.

Biofilm is a complex community of microorganisms residing within a polysaccharide and/or protein matrix. Biofilm can be produced by several microorganisms, including various bacteria and fungi. Nowadays, the resistance of biofilm-growing cells to antimicrobials originated from the structural nature of biofilms, and phenotypic alteration of sessile cells is becoming a global issue. Bacterial biofilms are important in various aspects of human health, including chronic infections, dental plaque, and infection of indwelling medical devices such as catheters. They are also a major problem in other industries, including oil recovery, drinking water distribution, papermaking, metalworking, and food processing. Estimates indicate that more than 80% of infectious diseases are biofilm-derived. The aim of this study is to describe mechanisms of antibiotic resistance to provide a better perspective on how to manage it. Moreover, the current strategies for biofilm inhibition were described. Considering that plants are a valuable source of abundant natural chemicals to create prophylactic and therapeutic medicines against biofilm-based infections, significant natural compounds with anti-biofilm properties were highlighted. Finally, natural anti-biofilm compounds under clinical trial evaluation were summarized to provide a background for more extensive researches and assist in opening a new window to novel treatments.