טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentCroitoru Sadger Tsuf
SubjectPolymersomes Based on Low Molecular Weight Multi-Armed
PEG-PCL
DepartmentDepartment of Biotechnology and Food Engineering
Supervisor Assistant Professor Boaz Mizrahi
Full Thesis textFull thesis text - English Version


Abstract

In recent years, significant progress has been made in the research of nanoparticles, mainly concerning their important role in drug delivery systems for poorly water-soluble drugs. Polymersomes, synthetic version of liposomes, are widely used as drug delivery system however they have shortcomings in drug-eluting properties that are attributable to the high molecular weight of the copolymers forming their membrane.  In this research, we demonstrated how novel class of polymersomes from very short, liquid to soft star-shaped copolymers can be empowered to form an efficient drug delivery system. The main goals of this study were: (1) to synthesize a series of PEG4-PCL copolymers with various PCL lengths; (2) to characterize the copolymers and monitor their aqueous behavior; (3) to study the size and morphology of the formed structures and; (4) to load the various copolymers with model drug and to study the effect of PCL length on the release profiles.

We synthesized a series copolymers consisting of a four armed low molecular weight (Mw = 2000 Da) Poly(Ethylene Glycol) (PEG) core and Poly(Caprolactone) (PCL) segments in order to form (PEG4-PCL) of various lengths. In two samples (PEG4-PCL 10:2 and 10:4 monomer ratio), the PEG segments weighed more than the PCL segment (1:0.4 and 1:0.8, accordingly). Another sample had a similar weight ratio (10:5 monomer ratio equivalent to 1:1.2 weight ratio), and in two samples (PEG4-PCL 10:6 and 10:20) the weight ratio was in favor of the PCL segment ( 1 : 1.5 and 1 :5, accordingly).  The synthesized copolymers undergo self-assembly in water into a stable, nano-sized rod or a spherical shape polymersomes. Increasing the molecular weight (Mw) of the hydrophobic moieties the critical micelle concentration (CMC) value is decreased accompanied with the tendency to form a more spherical structure. The poorly water-soluble anticancer drug Camptothecin (CPT) was loaded into the fabricated polymersomes, resulting in a high drug loading content, and released over a period of 7 days. This biocompatible system could potentially deliver a variety of drugs intracellularly in a rapid yet controlled manner, which is a desirable trait for various clinical conditions as well as for biomedical applications.