Antibacterial Research On Baicalin-loaded Nano-Polydopamine Combined With Photothermal Therapy

BackgroundThe active ingredients of Chinese medicines represented by baicalin play an important role in modern medical care and have a variety of pharmacological activities.However,it cannot be widely used clinically because of low solubility,poor stability and low bioavailability.It may help overcome the shortcomings of Chinese medicine by synthesising nanocarriers with nanotechnology to mediate drug delivery.The optimized and regulated polydopamine can be loaded with Chinese medicine and be functionally modified,achieving the intelligent and personalized treatment goals of Chinese medicine.In addition,polydopamine can mediate new treatment strategies such as photothermal therapy and further enhance the efficacy of Chinese medicine.Chinese medicine has unique advantages in many fields.In the field of bacteriostatic treatment,the emergence of bacterial infections,especially resistant bacteria,is a global public health challenge.Chinese medicine is not prone to drug resistance with low side effects,which takes unique advantages.ObjectiveIn this study,polydopamine loaded with baicalin(baicalin@PDA)were synthesized,and the antibacterial therapeutic effect of baicalin@PDA were explored from the two dimensions of computer simulation theory research and biological performance experimental research.Therefore,it can provide a basis for developing new and modernized application programs of Chinese medicine.MethodsComputer theory simulation1.The finite-difference time-domain simulation was used to simulate the changes of the ultraviolet-visible light(UV-Vis)spectra of PDA and mesoporous polydopamine(MPDA)nanoplatforms before and after baicalin loading;2.Monte Carlo method was used to simulate the drug release process of two drug delivery system under different bacterial efflux mechanisms.Antibacterial experiment of baicalin@PDA1.The UV-Vis spectrum and fluorescence spectrum of baicalin were tested to determine the optical quantitative method of baicalin;2.Preparation and characterization of PDA and MPDA nanoplatforms,and calculation of their drug loading efficiency and loading capacity for baicalin;3.The temperature changes of PDA and MPDA under laser irradiation were recorded using thermal imaging method to evaluate their photothermal performance;4.The cell viability of HaCaT cells and NIH3T3 cells co-cultured with baicalin was tested by MTT assay;5.The bacteriostatic activity of baicalin against Escherichia coli,Staphylococcus aureus and Pseudomonas aeruginosa was tested by concentration gradient dilution method;6.The susceptibility of Staphylococcus aureus and Pseudomonas aeruginosa to baicalin or PDA,and to PDA or baicalin@PDA-mediated PTT were tested by inhibition zone method;7.Staphylococcus aureus was treated with baicalin,PDA and baicalin@PDA for PTT.The survival status of bacteria was observed by fluorescence microscope.8.The model of mouse Staphylococcus aureus wound infection was made for PTT with baicalin,PDA and baicalin@PDA.The wound healing was recorded,and indicators such as body weight and neutrophil percentage were monitored.9.Mouse wounds were stained with HE,Masson and Sirius Red for pathological sections.Important organs of mice were stained with HE and the blood biochemical function was tested in order to evaluate the toxicity in vivo.ResultsComputer theory simulation1.The intensity of the baicalin absorption peak was changed.After being loaded on the PDA,the short-wavelength absorption peak was strengthened,and the long-wavelength absorption peak was weakened;2.When baicalin@PDA releases the drug inside the bacteria,the effective rate of baicalin is higher than 40%,which is better than the external release of the bacteria.MPDA is more effective than PDA in number of bacteria killed.Antibacterial experiment of baicalin@PDA1.In the concentration range of 2-80 ?M,baicalin can be quantitatively evaluated by UV-Vis spectrum.Baicalin is fluorescent;2.PDA and MPDA have high drug loading efficiency for baicalin,which is related to electrostatic adsorption;3.MPDA is better prepared by ultrasonic extraction method,whose mesoporous pore size is mainly 5nm;4.PDA and MPDA have high photothermal conversion efficiency and good photothermal stability,whose photothermal performance has concentration and power dependence;5.Baicalin exhibits low cytotoxicity and good biocompatibility.Baicalin can inhibit the growth of Escherichia coli,Staphylococcus aureus,and Pseudomonas aeruginosa and reduce their number;6.Baicalin@PDA can efficiently kill Staphylococcus aureus and Pseudomonas aeruginosa through photothermal therapy.In addition,baicalin and nanoplatform show synergistic effect in photothermal treatment.The compound antibacterial performance is higher than that of PDA alone.7.Baicalin@PDA can accelerate the healing of acute bacterial infectious wounds in mice and effectively inhibit the wound bacteria when combined with PTT.Baicalin@PDA can reduce the percentage of neutrophils in the acute phase and reduce collagen deposition with low toxicity when used externally.Conclusion1.Computer theoretical simulations show that the release of drugs through PDA and MPDA can effectively increase the baicalin utilization rate and the sterilization amount;2.Both PDA and MPDA are good baicalin-loaded nanocarriers with excellent photothermal performance,which can achieve high-efficiency adsorption;3.MPDA may be a potential drug loading nanocarrier for macromolecular Chinese medicine;4.Baicalin@PDA-mediated PTT has high-efficiency spectral sterilization,in which baicalin and PTT have a synergistic promotion effect;5.Baicalin@PDA can effectively inhibit bacteria to shorten the acute infection period and accelerate the healing of acute bacterial infectious wounds in mice with PTT,which is a promising antibiotic-free bacteriostatic nano-system.