Experimental Study On The Fabrication And Characterization Of Drug-loaded Microcapsules

Drug loaded microcapsules have been used in many applications such as sustained drug release,targeted therapy,controlled delivery and fluorescence imaging.These microcapsules may overcome the limitations of the encapsulated therapeutic cargos by protecting cargo bioactivity,enhancing the absorption rate and extend the therapeutic life time.At present,one of the most commonly used methods to fabricate microcapsules is emulsification.Although it is simple,easy to operate,and highly productive,emulsification usually produces microcapsules with broad size distribution,low encapsulation efficiency and burst release of drugs.Therefore,it is important to fabricate microcapsules with uniform size,high encapsulate efficiency and easy control of process parameters.Coaxial electrospray method is an emerging method for producing microcapsules at low cost,high encapsulation efficiency,uniform size and controlled morphology.In this thesis,curcumin is chosen as a model drug to be encapsulated in PLGA(poly(lactic-co-glycolic acid))microcapsules by coaxial electrospray.We study the influence of flow rate and applied voltages on the cone-jet morphology of coaxial electrospray,the size distribution of microcapsules,the encapsulation efficiency and the in vitro release profiles.In addition,triple-layered microcapsules are fabricated by an enhanced tri-axial electrospray process.The particulate micro-scaffolds are fabricated by combining coaxial electrospray with pre-patterned and gold covered microelectrodes.Finally,the liquid-driven flow focusing method is used to fabricate curcumin-loaded microcapsules with a size distribution ranging from several micrometers to tens of micrometers.The details are described as follows.1.We use the coaxial electrospray process to encapsulate curcumin in a biodegradable PLGA shell to form microcapsules with core-shell structure,narrow size distribution and high encapsulation efficiency.We study the influence of outer liquid flow rate and applied voltages on the coaxial cone-jet morphology,size distribution of microcapsules.Comparing to the microcapsules fabricated by the emulsification method and single electrospray method,the microcapsules fabricated by coaxial electrospray have advantages in sustained and controlled drug release.The results show that the microcapsules fabricated by coaxial electrospray can enhance the bioavailability and avoid several disadvantages of curcumin,such as low water solubility,poor oral absorption,the low blood drug concentration and the short plasma half-life.2.We first report the maskless coaxial electrospray of three-dimensional(3D)polycaprolactone(PCL)particulate microscaffolds(PPMs)with the help of pre-patterned gold-covered electrodes.Three flow modes in the process can be identified clearly.The process parameters including liquid flow rate,applied voltages,substrate configurations and fabricating time are found to affect the geometry of PPMs.The in vitro release study of rhodamine B of PPMs presents a controlled and sustained drug release behavior by changing the geometry of PPMs and the outer liquid flow rate.3.The tri-axial electrospray is used to fabricate curcumin-loaded triple-layered microcapsules.We use water,acetone and milk as three phases to visualize the tri-layered cone.PLGA(50:50,Mw=10,000)and PLGA(75:25,Mw=50,000)are dissolved into acetone,respectively,to fabricate the microcapsules.We study the influence of liquid flow rates and the applied voltages on the morphology of tri-layered cone and the size distribution of microcapsules.The encapsulation efficiency and the release profiles in vitro of microcapsules are measured.4.We use the coaxial flow focusing to obtain the core-shell strictured drug-loaded microcapsules.In this thesis,we design and manufacture the core devices of liquid-driven flow focusing.The resultant microcapsules are uniform and have a high encapsulation efficiency.By adjusting the focusing,the outer and the inner liquid flow rates,we study the effects of the process parameters on the morphology of the cone and the size distribution of microcapsules.The cytotoxicity profiles of microcapsules are studied in SKOV-3 ovarian cancer cell lines using MTT assay.Moreover,we develop a scalable coaxial flow focusing device for larger throughput of microcapsules.