טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentJosef Elinor
SubjectControlled Release of Hydrophobic Drugs from Nanocarriers
Embedded in Alginate Hydrogels
DepartmentDepartment of Biotechnology
Supervisor Professor Bianco-Peled Havazelet
Full Thesis textFull thesis text - English Version


Abstract

Poorly water soluble compounds that promote health are very common. These include vitamins, (such as vitamin A), antioxidants (curcumin, carotenes), lipid bioactive lipids (omega-3, omega-6), peptides and drugs. This thesis presents an innovative methodology for sustained delivery of hydrophobic drugs using composite hydrogels, prepared by embedding oil-in-water microemulsions in alginate hydrogels. The hydrophobic nature of the microemulsion core enhances the solubilization of hydrophobic drugs, while the crosslinked matrix could be readily used as a solid controlled delivery vehicle. Ca. 10-nm microemulsions droplets were formulated from pharmaceutical accepted components. The composite gels showed capability of loading several hydrophobic compounds with a wide range of aqueous solubilities. Small angle X-ray and neutron scattering from composite gels show that both the droplets and the gel network preserve their structure when mixed together. The release behavior was similar for different microemulsion formulations, various drugs and increasing concentrations of a drug. However, the release could be controlled by manipulating the polymer and crosslinker concentration. These findings indicate that our system could potentially act as a generic system, where the properties of the release do not depend on the drug but rather on the attributes of the gel.

Achieving a dry easy-to-store delivery system based on composite hydrogels could be beneficial. We report on a new method to solidify self-microemulsifying drug delivery systems (SMEDDS)?their incorporation in sponges made from alginate. SMEDDS containing Nile red were gradually released from the sponges, at a rate that depended on the drying method. The combination of SMEDDS and sponges may be a way to overcome the disadvantages of each component separately, provide a solid dosage form for SMEDDS that can sustain the release of drugs and also enable utilization of hydrophilic sponges for the delivery of hydrophobic drugs

As a step toward unveiling the structure of composite gels, one has to understand the structure of alginate gels and solutions. We studied the conformation of alginate chains in solution, and examined several approaches for their modeling, taking into account inter-chain electrostatic interactions. Some of the models discussed have not been applied to experimental data before. To the best of our knowledge, this is the first time a complete physical modeling of alginate solutions is presented. By fitting the entire scattering curve, we derived the persistence length as a function of the polymer concentration. This allowed us to examine the electrostatic persistence length and the validity of the OSF theory.