Electrospun Composite Nanofibers Containing Nanoparticles For Controlled Release Of Multiple Drugs

Cancer relapse and metastasis tumor is very common in clinical, which is related to the incomplete surgical removal of tumor cells. Local administration of chemotherapeutics at the tumor site is effective to prevent cancer relapse and metastasis. Due to the complexity of tumor formation mechanism and the existence of multidrug resistance, it will not kill the tumor cells completely by using one drug alone. In addition, it is thought to enhance treatment effect by sequential and distinct release of drugs at the different growth cycle of tumor cells. Therefore, therapeutic efficacy can be maximized if two anticancer drugs with distinct characteristics and action mechanisms can be delivered to the same cell and release in a sequential way, which will play an important role in cancer therapy.In the paper, nanoparticle-contained composite nanofibers as a novel drug delivery system was successfully fabricated. It could encapsulate two drugs at the same time and showed different release behaviors due to their different distribution in the composite nanofibers. They were able to provide a good alternative for multiple drugs loading and programming the release of each drug for cancer chemotherapy. The following works were done in the thesis.①Dual-wavelength spectrophotometry was established to detect the concentration of rodamine B and naproxen at the same time. For rhodamine B the calibration curve was created at 554nm, where the drug gave its characteristic peak, while naproxen showed a characteristic peak at 330nm and reference wavelength at 369 nm. The average recovery rate of naproxen was 101.52±2.03%, RSD was 1.99%, and the correlation coefficient was 0.9999. The three data of rhodanmine B were 100.41±1,69%, 1.69%, and 0.9997, respectively.②Chitosan nanoparticles embedded levofloxacin were prepared via ionic gelation interaction. The preparation progress was optimized based on the encapsulation efficacy and size of nanoparticles. The optimistic conditions for preparations were as followes: the concentration of CS was 2.0mg/mL, TPP 0.7mg/mL, drug 0.2mg/mL and pH4.3. The average size was 388±17nm, and zata potential is +70.00±1.83mV. The morphology of nanoaprticles with a roughly spherical shape was analyzed using field emission scanning electron microscopy. The encapsulationt efficacy and drug loading capacity were 33.64±4.31% and 1.62±0.09%, respectively. Release process was more close to Higuchi equation and sustained drug release from nanoparticles was controlled by diffusion mechanism.③Drug loaded nanofibers were prepared using electrospinning with poly(ε-caprolactone) as a matrix and naproxen as a model drug. The results demonstrated that the concentrations of PCL and naproxen were important factors on the surface morphology and the drug release behavior of the electrospun fibers. The diameters of the fibers increased slightly with the increase of PCL concentration from 9% to 13%, while the drug concentration increased from 0.5% to 2%, it had no obvious effect on the diameters. Drug release behavior indicated that the drug loaded nanofibers showed a burst release with the increase of drug concentration, but they showed sustained release with the increase of PCL concentration. The nanofibers showed sustained release rate and the drug release experienced desorption and diffusion stages.④Nanoparticle-contained composite nanofibers with core-shell structure for controlled release of dual drugs were fabricated using rodanmine B and naproxen as model drugs. Two kind nanoparticles were prepared via ionic gelation interaction. Their size was between 380 and 550nm. Fluorescence microscopy and laser scanning confocal microscopy demonstrated that the nanoparticles were encapsulated within the composite nanofibers, forming core-sheath structures. The different release behaviors of two drugs were ascribed to their different distribution in the composite nanofibers. When rhodamine B was embedded into nanoparticles and naproxen was encapsulated in the PCL matrix, the release rate of naproxen was much faster than rhodanmine B. At 72h, their accumulated drug release was 60.53% and 18.15%, respectively. On the contrary, rhodanmine B released faster than naproxen, and they released to 99.66% and 51.47% at 72h, respectively. Therefore, Programmable release of both drugs could also be achieved by adjusting the distribution of two drugs in the core or shell of the composite nanofibers.