Sytze Buwalda1, Assala Al Samad2, Ayman El Jundi3, Audrey Bethry4, Youssef Bakkour5, Jean Coudane6, Benjamin Nottelet7. 1. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France. Electronic address: sijtze.buwalda@umontpellier.fr. 2. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France; Laboratory of Applied Chemistry, Faculty of Science III, Lebanese University, P.O. Box 826, Tripoli, Lebanon. Electronic address: assalasamad@hotmail.com. 3. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France; Laboratory of Applied Chemistry, Faculty of Science III, Lebanese University, P.O. Box 826, Tripoli, Lebanon. Electronic address: aymanjondi91@gmail.com. 4. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France. Electronic address: audrey.bethry@univ-montp1.fr. 5. Laboratory of Applied Chemistry, Faculty of Science III, Lebanese University, P.O. Box 826, Tripoli, Lebanon. Electronic address: ybakkour@ul.edu.lb. 6. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France. Electronic address: jcoudane@univ-montp1.fr. 7. IBMM (UMR5247), Univ Montpellier, CNRS, ENSCM, Montpellier, France. Electronic address: Benjamin.Nottelet@umontpellier.fr.
Abstract
HYPOTHESIS: The functionalization of poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) block copolymers with moieties allowing for core-crosslinking is expected to result in improved micellar stability and drug delivery properties. EXPERIMENTS: PEG-(PCL)8 star block copolymers were functionalized with pendant benzylthioether (BTE) groups by applying an anionic post-polymerization modification technique followed by photoradical thiol-yne addition of benzyl mercaptan. The micellar properties of PEG-(PCL)8 and PEG-(PCL-BTE)8 were studied and compared in terms of critical micelle concentration (CMC), size, morphology, drug loading and release and in vitro cytotoxicity. FINDINGS: In comparison with unmodified PEG-(PCL)8 micelles, PEG-(PCL-BTE)8 micelles exhibited a 15-fold lower CMC, a 15-fold smaller size and a 50% higher drug loading and encapsulation efficiency thanks to the presence of pendant benzyl groups which provide the possibility for micellar core-crosslinking via supramolecular π-π stacking and additional hydrophobic interactions. Whereas the PEG-(PCL)8 micelles showed significant aggregation during in vitro cytotoxicity experiments, the PEG-(PCL-BTE)8 micelles showed no signs of aggregation and were capable of solubilizing high concentrations of curcumin, resulting in a significant decrease in MCF-7 cell viability after 48 h. Their ease of synthesis combined with promising results regarding drug delivery make the PEG-(PCL-BTE)8 micelles appealing for application in the field of encapsulation.
HYPOTHESIS: The functionalization of poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) block copolymers with moieties allowing for core-crosslinking is expected to result in improved micellar stability and drug delivery properties. EXPERIMENTS: PEG-(PCL)8 star block copolymers were functionalized with pendant benzylthioether (BTE) groups by applying an anionic post-polymerization modification technique followed by photoradical thiol-yne addition of benzyl mercaptan. The micellar properties of PEG-(PCL)8 and PEG-(PCL-BTE)8 were studied and compared in terms of critical micelle concentration (CMC), size, morphology, drug loading and release and in vitro cytotoxicity. FINDINGS: In comparison with unmodified PEG-(PCL)8 micelles, PEG-(PCL-BTE)8 micelles exhibited a 15-fold lower CMC, a 15-fold smaller size and a 50% higher drug loading and encapsulation efficiency thanks to the presence of pendant benzyl groups which provide the possibility for micellar core-crosslinking via supramolecular π-π stacking and additional hydrophobic interactions. Whereas the PEG-(PCL)8 micelles showed significant aggregation during in vitro cytotoxicity experiments, the PEG-(PCL-BTE)8 micelles showed no signs of aggregation and were capable of solubilizing high concentrations of curcumin, resulting in a significant decrease in MCF-7 cell viability after 48 h. Their ease of synthesis combined with promising results regarding drug delivery make the PEG-(PCL-BTE)8 micelles appealing for application in the field of encapsulation.