Preparation And Study Of PH Sensitive Gelatin/PLCL Dual-drug Loaded Fiber Scaffolds By Coaxial Electrospinning

Cancer endangers human health seriously.Now,we did not find a particularly effective way for cancer treatment.Surgery,radiotherapy and chemotherapy are the main methods for the treatment of cancer.The earliest treatment for cancer is surgery,and it is also the first choice for early cancer treatment.However,surgical treatment can't achieve good therapeutic effect,since the metastasis of cancer cells is easy to cause cancer recurrence.Electrospinning has been the focus of attention since its emergence.Electrospun fiber has many advantages,such as large specific surface area,high porosity.It has been applied in environmental engineering,wound dressing,material support,biological medicine and so on.Coaxial electrospinning is based on electrospinning,which has the same principle with electrostatic spinning.It gives more functions to electrospinning.Electrospun fiber membranes can be used as drug carriers,and the addition of smart materials can achieve the function of drug controlled release.In this study,hydrophilic gelatin was chosen as shell material to load ciprofloxacin,and sodium bicarbonate was added with emulsion method.The core layer material was hydrophobic poly?lactide-co-?-caprolactone??PLCL?,loading the anticancer drug doxorubicin hydrochloride?DOX?,hexafluoroisopropanol?HFIP?was selected as solvent.A dual drug loaded nanofiber scaffold with pH sensitivity was prepared by coaxial electrospinning for postoperative cancer treatment.Specific research contents are as follows:?1?Gelatin fibers?GS^-,GS⁺,G^-,G⁺?were prepared by electrospinning,and fiber hydrophilicity and hydrophobicity,in vitro drug release,antibacterial,cytotoxicity were studied.The results showed that the drug-loaded gelatin fiber had good hydrophilicity,good biocompatibility and antibacterial activity,the addition of sodium bicarbonate using the emulsion method showed obvious pH sensitivity.?2?Preparation of PLCL fibers by electrospinning?PS^-,PS⁺,P^-,P⁺?,study the hydrophilicity and hydrophobicity,in vitro drug release,antibacterial,and cytotoxicity of the fibers.The results showed that the drug loaded PLCL fiber was hydrophobic material with good biocompatibility and antibacterial activity.After adding sodium bicarbonate,the fibers did not exhibit pH sensitivity.?3?Gelatin/poly?lactide-co-?-caprolactone??PLCL?coaxial fiber scaffolds?G⁺/P⁺,GS₁⁺/P⁺,GS₂⁺/P⁺,GS₃⁺/P⁺,G^-/P^-,GS₁^-/P^-,GS₂^-/P^-,GS₃^-/P^-?prepared by coaxial electrospinning.The shell was made up of a mixture of gelatin and sodium bicarbonate?SB?,SB was included in the shell to provide pH-sensitivity.The shell was also loaded with anti-inflammatory drug ciprofloxacin;the core comprised poly?lactide-co-?-caprolactone?with the chemotherapeutic doxorubicin hydrochloride?DOX?.Scanning electron microscopy?SEM?showed that the fiber scaffolds were smooth,no beads appeared,and the fiber diameter was uniform.A clear coaxial structure was observed by transmission electron microscopy?TEM?,and sodium bicarbonate particles were visible in the shell.Fourier transform infrared spectroscopy?FTIR? and X-diffraction?XRD?showed that the gelatin-PLCL coaxial drug loaded fiber scaffolds were prepared successfully.?4?Study the application of gelatin/PLCL coaxial dual-drug loaded fiber scaffolds in the postoperative treatment of cancer,the hydrophilicity and hydrophobicity of the fiber scaffolds,drug release in vitro,antibacterial activity,cytotoxicity,mechanical properties and degradation properties were studied respectively.Those results showed that the coaxial fiber scaffolds were hydrophilic due to the hydrophilic gelatin,which were good for cell growth.The addition of ciprofloxacin made the fibers antibacterial.Drug release experiments showed that the release of ciprofloxacin and DOX had pH sensitive because of the addition of sodium bicarbonate.The DOX release from the core layer slowly,due to the encapsulation of the shell gelatin.Simultaneously,drug release and drug controlled release were achieved.The addition of ciprofloxacin made the fiber scaffolds antibacterial.The coaxial fiber scaffolds had high biocompatibility,non-toxic side effects on cells,and the addition of DOX inhibited the growth of cancer cells.The scaffold had good mechanical properties,which belongs to biodegradable material and meets the demand of tissue engineering scaffolds.