The Drug Delivery System Based On The Swelling Core Structure For Differential Release Of Multiple Drugs

Incomplete removal of tumor cells is one of the important reasons for leading to tumor recurrence and metastasis. Using implants for local chemotherapy drugs at the the tumor site after removing tumor cells, it plays an important role for increasing the effectiveness of cancer treatment and prevention of recurrence of the tumor. Due to the diversity of the the mechanism and role of the tumor targets, the Single-drug factors can not achieve the purpose of killing the tumor cells, and may easily to lead to multidrug resistance. Moreover, strategy of combined administration of multiple drugs could adjust various siginal transmission channels in the regulation of tumor cell proliferation, invasion, and metastasis stages, through the synergy and complementary effects between drugs. Therefore, it has great significance for the postoperative treatment of tumors to integrate the advantages of drug combination and local treatment, and establish a multi-drug delivery system based on the composite structure of carrier. Through the regulation of drug delivery route, loading methods and the application of functional materials, release of drugs could be well controlled in the operating site.In the paper, the core-shell nanofibers based on swelling core as novel drug delivery system were successfully fabricated. It could encapsulate two drugs with different molecular weight at the same time and showed different release behaviors due to their different drug delivery path and the swelling of the loading area. They can provide an alternative for loading multiple drugs and achieving differential release of each drug for cancer chemotherapy. The following works were done in the thesis.①Dual-wavelength spectrophotometry was built to detect the concentration of rodamine B and BSA at the same time. For rhodamine B the calibration curve was created at 553nm, while BSA showed a characteristic peak at 273nm and reference wavelength at 500nm. The average recovery rate of BSA was 100.14±0.97%, RSD was 1.99%, and the correlation coefficient was 0.9993. The three data of rhodanmine B were 100.50±1.53, 0.97%, and 0.9992, respectively.②Preparation of the fibers with complete core-shell structure was the basis for achieving the differential release of multiple drugs. Polyvinyl alcohol (PVA) and poly (ε-caprolactone) (PCL) was used for preparing PVA / PCL fibers with core-shell structure. W/O type of PVA/PCL uniform emulsion was prepared with PVA aqueous solution as water phase, PCL chloroform solution as the oil phase, and Span 80 as emulsifier. When the water phase and oil phase volume ratio was 1:10, the surface of PVA / PCL fibers were smooth, and the average fiber diameter was of 500±35nm. The core-shell structure of the fibers was complete, and the average diameter of the core fibers was 420±40nm.③The swelling property of the core fiber was important for achieving the differential release of multiple drugs. Three PVA with the different swelling degrees (117-PVA, CST-PVA, 217-PVA) were used as the nuclear part of fiber in this paper, and the morphology changes caused by core swelling were also researched. Surface of three kinds of PVA / PCL fibers was smooth, and a little differences of average diameter were observed, RSD was 1.45%. The membrane of three PVA / PCL fibers immersed in phosphate buffer solution achieved maximum swelling degrees at 8h. The maximum degree of swelling was 10.07±0.15%, 62.4±0.22%, 13.2±0.17%, respectively. All of the fibers didn't appear breakage and dissolution phenomenon, and the original three-dimensional structure was not damaged after immersing 6d. The average diameter of these fibers were increased, especially (CST-PVA) / PCL increased 81.8±2.3%. After 8h immersion of (CST-PVA) / PCL fibers, average fiber diameter increased 138.2±6.1%, of which the nuclear part increased 127±11.4%, and shell part increased 20±3%. Swelling of the fiber is mainly caused by the swelling of the nuclear part, which plays a major role.④Base on the preparation of core-shell structure PVA/PCL fibers and the researches of fiber morphology influenced by the swelling nuclear part, the core-shell structure fiber (BSA+CSC+CST-PVA)/(RhB+PCL) contained both RhB, BSA, and CSC was prepared. When the BSA content was less than 0.04g/mL and CSC content was less than 0.03g/mL in the aqueous emulsion, uniform and stable W/O type emulsion could be prepared. The drug-loaded fiber was uniform and smooth. The diameter was 669±2.1nm, of which the nuclear part was 425±4.5nm. Images of FM displayed that BSA was encapsulated completely in nuclear part of the core-shell structure CST-PVA/PCL fiber. In the emulsion electrospinning process, there was no chemical reaction between polymer materials and the drugs. RhB was loaded in the PCL shell of composition fiber, which swelling properties is lower. Fitting results showed Higuchi equation fit well in the first 2h, there was a burst release for RhB embedded in the fiber; the first order equation fit well during the mid-22h, RhB released as the desorption of fibers. Higuchi equation fit well in the last release stage. When fiber shell was fully infiltrated, RhB was released by diffusion. BSA was encapsulated in the core of the CST-PVA, which possessed good swelling property. Diffusion-relaxation equation can be well fitted its release profile. BSA released slowly by diffusion early in the swelling. With the continued absorption of fluid, CST-PVA swelled continuously, the release rate of BSA increased until the fiber swelling was equilibrium. BSA released by diffusion after swelling equilibrium. The model drugs, RhB and BSA, were loaded in the polymer materials with different swelling properties at different positions, so they have distinct release paths and diverse release principles, thus the differences in drug release behavior were led to.