Preparation Of PH-responsive Nanocarriers And Study On Their Mucus Permeability

Local nano-drug delivery system can avoid systemic toxicity and ineffective treatment of traditional systemic administration.At present,low mucus penetration ability and low cellular uptake limit the effectiveness of local drug administration in mucosal tissue because of the rapid foreign particulates and pathogens removal property of the high viscoelastic and adhesive mucus layer.In this work,we design a kind of pH-responsive mucus-penetrating nanoparticles(pMPP)for female vaginal treatment,which is expected to be applied to the controllable drug release and fluorescence imaging.The details are as follows:(1)Preparation and characterization of pH-responsive amphiphilic polymer.Amphiphilic polymer conjugate(PLGA-N=CH-PEG)was designed and synthesized.The ~1H NMR and fluorescence spectrophotometer results showed that PLGA-N=CH-PEG was synthesized successfully and had perfectly self-assemble properties.(2)Preparation and characterization of pH-responsive nanocarriers.The obtained PLGA-N=CH-PEG conjugates self-assembled into nanocarriers.The ~1H NMR,dynamic light scattering and transmission electron microscopy results showed that nanocarriers were assembled successfully with the spherical structure and homogeneously distributed at around 78 nm in diameter.The surface potential of nanocarriers was neutral and the hydrazone bonds on the nanocarriers had good pH sensitivity.(3)Study on mucus permeability of pH-responsive nanocarriers.Multiple particle tracking in human cervicovaginal mucus suggested that the obtained nanocarriers had perfectly mucus permeability.Cytotoxicity assay and histology in the mouse vaginal tract showed the low toxicity of nanocarriers.The results of cellular uptake and cellular uptake of nanoparticles in mouse vaginal tissue showed the high cell internalization efficiency of nanocarriers.Retention and distribution of nanoparticles in mouse vagina showed that the obtained nanocarriers had perfectly mucus permeability and cell internalization efficiency in vivo.In short,all of the results showed that the pH-responsive mucus-penetrating nanocarriers were prepared successfully,which may be promising nanocarriers for mucus diagnosis and therapy applications.