טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAbu Saleh Doaa
SubjectDesign of core anchored polymeric micelles as novel
nanocarriers for drug solubilization and
stabilization
DepartmentDepartment of Materials Science and Engineering
Supervisor Professor Alejandro Sosnik
Full Thesis textFull thesis text - English Version


Abstract

Polymers play a major role in pharmaceutical research and development in general and drug delivery in particular by providing flexible platforms for controlled release and targeting. More than 50% of the approved drugs are poorly water soluble according to the Biopharmaceutics Classification System (BCS). Polymeric micelles (PMs) represent a nanotechnology platform largely used to solubilize and stabilize drugs physically and chemically and to increase their oral bioavailability. PMs are the result of the self-assembly of amphipathic copolymer chains in water above the critical micellar concentration (CMC) and they display two domains, a hydrophobic core and a hydrophilic corona. The hydrophobic core fits the encapsulation of poorly water-soluble molecules, and the corona that is in direct contact with the medium, stabilizes the aggregate and tunes the release of the cargo. However, a main challenge is preventing the disassembly of PMs under dilution in the body fluids, which leads to uncontrolled release of the encapsulated cargo. This work investigated a new amphiphile architecture, namely core-anchored PMs, to improve the physical stability and performance of these nanocarriers. In this framework, two kinds of molecular anchors were used for the conjugation of amphipathic monomethoxy-poly(ethylene glycol)-b-poly(epsilon-caprolactone) diblocks (MPEG-PCL): (i) organic cyclodextrins (CDs) and (ii) inorganic carboxylated nanodiamonds (cNDs) and carboxylated red fluorescent nanodiamonds (cRFNDs). Characterization studies were conducted by 1H-NMR, FTIR and TGA and confirmed the conjugation of amphiphiles to the surface of both inorganic nanoparticles, while the approach based on CDs was less successful. In addition, transmission electron microscopy (TEM) revealed the presence of a thick polymeric layer on top of the nanodiamonds. Dynamic light scattering and nanoparticle tracking analysis were used to measure the size and the stability of the nanoparticles in water. Cell viability was evaluated in Caco2 cell line, an in vitro model of the intestinal epithelium. Encapsulation of the anti-helmintic drug nitazoxanide increased from 11 to 700 µg/mL in a 0.4% w/v system, reaching 17.5% w/w drug loading. Results support the feasibility of this novel flexible and modular strategy for the development of more robust nanotechnology platforms for drug delivery.