Researchers are focusing their attention on designing Nano-carriers for the controlled delivery and sustained release of protein- or peptide-based therapeutics. Proteins are believed to be more efficient for treatment of many diseases as opposed to small molecules. However, there are a number of issues that should be addressed concerning proteins in nanoformulations. Proteins have a sensitive tertiary structure that is easily degraded by temperature and losses its activity when exposed to solvents.
For this reason, a number of production procedures have been proposed in a move to preserve the specific structure and activity of proteins. In addition, particles produced for pharmaceutical applications are facing some challenges such as restricted choice of solvents used and reduced amount of residual solvent allowed in the products.
Therefore, supercritical carbon dioxide has been proposed as an alternative medium for the nanocarriers synthesis. Supercritical carbon dioxide is an inexpensive solvent, which is non-flammable and non-toxic. Moreover, supercritical carbon dioxide can be easily removed from the reaction medium by depressurization which enables obtaining products as free-flowing powders without solvent residues.
2-hydroxyethyl methacrylate (HEMA) based cross-linked particles (nano/microgels) present high biocompatibility and can function as potential carriers in drug delivery and tissue engineering. Nanoparticles based on (co)polymers of 2-hydroxyethyl methacrylate can advantageously be prepared by dispersion polymerization. However, this process necessitates the use of organic solvents, and therefore subsequent purification and drying steps are required to harvest the particles from the reaction medium.
Researchers led by Professor Christine Jérôme from the University of Liege in Belgium, investigated the use of perfluorinated copolymers as stabilizers for the preparation of cross-linked 2-hydroxyethyl methacrylate nanoparticles in supercritical carbon dioxide in place of trifluorotoluene. This was in a move to study the feasibility of implementing the supercritical carbon dioxide as a green polymerization medium. Their research work is published in Journal of Materials Chemistry B.
The research team tested various architectures of copolymers for their surface tension, cloud point, and stabilizing agents. They found the diblock architecture to be the best candidate to form well-defined spherical particles. In this study, the authors reported the mildest synthesis conditions (temperature of 35°C, pressure of 300bars) in supercritical carbon dioxide affording monodisperse poly(HEMA) particles.
With the goal to tailor the particles size, the authors also investigated different compositions of the diblock architecture by implementing three chain lengths of carbon dioxide-phobic block. The authors defined the diblock composition which led to discrete networks with the lowest size of about 200nm. The size of the particles could be tuned by pressure, temperature, and the composition of the amphiphilic block copolymers.
The findings of their study will pave way for the integration of temperature and solvent sensitive therapeutic agents. These agents can be introduced in the reaction mixture from the initiation of in-situ encapsulation.
R. Parilti, D. Alaimo, B. Grignard, F. Boury, S. M. Howdle and C. Jérôme. Mild synthesis of poly(HEMA)-networks as well-defined nanoparticles in supercritical carbon dioxide. Journal of Materials Chemistry B, volume 5 (2017), pages 5806—5815.
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