The work performed during the project has achieved most of its objectives and milestones for the period, with relatively minor deviations.
Scientific objectives
• Design of a pH-cleavable chemistry strategy to obtain polymers that while assembling under physiological pH could degrade and disassemble at the slightly acidic pH of the lysosome
• Synthesis of cyclodextrin derivatives (CDs) to be incorporated onto the polymers through such pH-cleavable linkage
• Synthesis of bis-functional poly-ε-caprolactone polymers (PCL) of different lengths through a novel microwave-assisted procedure developed during the project
• Conjugation of the CD onto the PCL in order to obtain CD-appended polymers (CD-PCL)
The results of this first block, as per WP1, have already been published in a scientific paper A. Puglisi, et al, Biomacromolecules 2019, 20, 4001−4007
• Study of the self-assembling properties of the different CD-PCL polymers and selection of the best candidate in terms of stability of the CD-based polymersome microparticles (CD-PMs).
• Study of the hydrolysis behavior of the CD-PMs at different pHs
The results of this first block, as per WP2, have already been published in a scientific paper A. Puglisi, et al, Biomacromolecules 2019, 20, 4001−4007
• Cytotoxicity investigation of the CD-PMs
• Cellular uptake of CD-PMs
• BBB-crossing on models for CD-PMs
• Cholesterol-mopping activity for CD-PMs
Some of the results of this first block, as per WP3, have already been published in a scientific paper A. Puglisi, et al, Biomacromolecules 2019, 20, 4001−4007
Besides, a perspective article to set the project in the context of the current state-of-the-art about the importance of cyclodextrin-cased macromolecular systems as cholesterol-mopping therapeutic agents in Niemann-Pick Disease Type C was published:
o A. Puglisi, et al, Macromolecular Rapid Communications 2019, 40, 1800557
