Abstract
Drug delivery is important for the transport of pharmaceutical compounds into the body to achieve the desired therapeutic effect. Targeted drug delivery technology can increase the concentration of medication in the desired site compared with other sites and can improve drug effectiveness. Precise control of the delivered amount and the position of drugs can avoid drug wastage and result in the accurate adjustment of a drug’s dosage and effect area. Accurate delivery of the precise amount of a drug to a specific location will highly impact various clinical applications. This thesis uses multifunctional poly(D,L-lactide-co-glycolide (PLGA)-based microspheres and non-invasive optical tweezers manipulation to demonstrate the effect of different delivery amounts and locations of drugs in living zebrafish embryos. This research is conducted on the basis of the following three aspects.First, multifunctional PLGA-based microspheres are designed and manufactured. This kind of microspheres has biodegradable and biocompatible properties, as well as drug-carrying capability. The microspheres are also fluorescent. Thus, they can be easily found, detected, and counted in vivo. The microspheres have a spherical shape, with a size of a few micrometers. This design can lead to the easy capture of these microspheres by optical tweezers. Experimental results show that the designed PLGA-based microspheres can be manipulated by optical tweezers, can easily be detected in living zebrafish embryos, and can be degraded in living zebrafish without harmful effect.
Second, vascular endothelial growth factor (VEGF-a) encapsulated in PLGA-based microspheres are used to demonstrate the precise amount of drug released in zebrafish embryos and its effect. VEGF ligands are the main mediators of vasculogenesis and angiogenesis development in zebrafish embryo. VEGF-a is one of the most important ligands for angiogenic function. The fluorescence density of blood vessels in zebrafish with different numbers of injected microspheres can be assessed to examine the growth status of zebrafish blood vessels. The influence of different drug amounts on the growth of blood vessels in the yolk of zebrafish embryos can be examined precisely.
Third, the precise location control of PLGA-based microsphere to the desired site in vivo is completed by the optical tweezers manipulation system. This platform contains three modules for execution, sensing, and control. The executive module includes a XYZ motorized stage and a holographic optical trapping device. The PLGA-based microsphere is transported by optical tweezers manipulator in the yolk sac of transparent living zebrafish. The position error of the tracking trajectory of microspheres trapped by optical tweezers approached zero, thereby showing satisfactory position control performance.
This study presents a new approach for the precise control of the delivery amount and location of drugs in vivo through the use of multifunction PLGA-based microspheres and a non-invasive optical tweezer manipulation. The approach has been demonstrated successfully in living zebrafish embryos. Different effects were obtained due to differences in delivery amount and location of drugs, thereby highlighting the importance of precise control of amount and position of drug delivery. Precise control of amount and location of delivered drugs in vivo will have significant impact on targeted therapy.
| Date of Award | 4 Jun 2019 |
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| Original language | English |
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| Supervisor | Dong SUN (Supervisor) |