Jin Zhang, Chuan-Zhen Ye, Ze-Yu Liu, Qian Yang, Yong Ye

Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, Peoples Republic of China

Correspondence: Yong YeDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, Peoples Republic of ChinaTel +86-20-87110234Email yeyong@scut.edu.cn

Background: Bacterial resistance to antibiotics is a persistent and intractable problem. The sapogenin isolated from the seeds of Camellia oleifera can inhibit antibiotic-resistant bacteria after structural modification.Purpose: This study aims to improve sapogenins antibacterial activity and avoid bacterial resistance based on nano-preparation with photo responsiveness.Methods: The liposome shell material of carboxymethyl chitosan-phosphatidyl ethanolamine (CMC-PE) was prepared using amidation reaction, and photo-responsive cationic (PCC) liposomes containing Camellia sapogenin derivative (CSD) and photosensitizer pheophorbide-a were prepared by film dispersion method. Encapsulation efficiency, drug loading, zeta potential, particle size distribution, morphology and stability of the PCC liposomes were determined by HPLC, particle size analyzer, transmission electron microscopy (TEM) and fluorescence microscopy. Photo-responsive release of CSD in the PCC liposomes was determined by laser (0.5 mW/cm2) at 665 nm. Antibacterial activity of the PCC liposomes with or without irradiation was analyzed by MIC50, MBC, MBIC50, and bacterial morphology to evaluate the antibacterial effects on amoxicillin resistant Escherichia coli and Staphylococcus aureus.Results: Size distribution, zeta potential, encapsulation efficiency and drug loading of the PCC liposomes were 189.23 2.12 nm, 18.80 1.57 mV, 83.52 1.53% and 2.83 0.05%, respectively. The PCC liposomes had higher storage stability and gastrointestinal stability, and no obvious hemolytic toxicity to rabbit red blood cells and no cytotoxicity after incubation with Hela cells. The photosensitizer pheophorbide-a was uniformly dispersed in the phospholipid layer of the PCC liposomes and increased the CSD release after irradiation. The PCC liposomes could bind to bacteria and impaired their morphology and structure, and had significant bactericidal effect on amoxicillin resistant E. coli and S. aureus.Conclusion: The photo-responsive PCC liposomes are efficient antibacterial agents for avoidance of bacterial resistance against antibiotics.

Keywords: Camellia sapogenin derivative, photo-responsive cationic liposomes, carboxymethyl chitosan, antibacterial effects, antibiotic substitutes

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