טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentMun Alexandra
SubjectControlling Drug Release from Alginate Beads using
Embedded PCL Microbeads
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Dror Seliktar
Full Thesis textFull thesis text - English Version


Abstract

In recent years there has been a growing demand for research and development in the field of controlled release (CR) technology. CR has been applied in the biomedical, food, pharmaceutical and agricultural industries to deliver biomolecules, drugs, pesticides, herbicides and fertilizers. The core concept of all delivery vehicles is to release a defined quantity of various active substances over the course of a specific duration. Thus, materials used in the production of CR devices may be engineered to provide exacting specification of the intended use in terms of release profiles and biodegradation. The stability of the core material can be modified by altering the composition, and the release characteristics can be modified by changing the formulation. In the present study, we aimed to create a novel agricultural CR device using two polymeric systems that have been predominantly employed in biomedical applications: Alginate and Polycaprolactone (PCL). This is done by forming a combined alginate and PCL device that utilizes the advantages of each polymer type for biodegradation and controlled release. Paclobutrazol (PBZ) was chosen as the active ingredient (AI) to serve as a model substance for a common agrochemical used for vegetative grow control. The polymeric device was designed to release PBZ for 4 years with a single treatment.  The device was composed of alginate capsules with embedded PCL microbeads. Montmorillonite (MT) clay minerals were added to the alginate in order to increase physical stability of the capsules. Alginate capsules with MT and PCL beads were prepared using an extrusion method with the help of an encapsulation machine. In addition, a coating technique for the alginate capsules was developed to slow the release of PBZ. In order to test the coating efficiency, the surface morphology of the resultant capsules was characterized by scanning electron microscopy (SEM) and water immersion tests were performed for stability and release measurements.  Bioassays were performed both in accelerated laboratory conditions and field conditions. The aim of the accelerated experiments was to test the effect of released PBZ with increasing amounts of irrigation water. The results showed a capability to control the size of PCL microbeads through modification of homogenization speed and emulsifier concentration. Enlargement of PCL microbead size had a negative effect on release of AI from the alginate capsules. With regard to coating of alginate capsules, a special device for spray-drying was constructed. SEM images of the coated capsules showed the formation of a thin film with improved uniformity as the number of coating cycles was increased. Testing for AI release in water confirmed delay of release for coated alginate capsules. Addition of clay to alginate increased swelling stability in water. Growth of oatmeal was affected by the controlled release of PBZ by all irrigation treatments. A preliminary field experiment was observed during two consecutive seasons. The final product was also environmentally friendly and has the potential to be used as a carrier for different substances in the agrochemical industry.