Mesenchymal Stromal Cells Loading Curcumin-INVITE-Micelles: a Drug Delivery System for Neurodegenerative Diseases

This work reports on the formation of a carrier-in-carrier device for the systemic delivery and targeting
of hydrophobic drugs mediated by micelle-loaded mesenchymal stromal cells (MSCs) (carrier-in-carrier)
to be administered by intravenous injection. The innate ability of MSCs to reach injured tissues such as
the central nervous system or other damaged tissues, is the key for the second order delivery and first
order targeting. Inulin-d-alfa-tocopherol succinate micelles (INVITE M) are able to incorporate highly
hydrophobic drugs and, due to their dimensions (≈7 nm diameter), to penetrate the cell membrane
easily and quickly. This study demonstrates that the curcumin loaded micelles (INVITE MC), sterilized by

filtration, reached the maximum loading in MSCs in few minutes and that the loading was concentration-
dependent. When “naked” curcumin was used, an evident cytotoxicity on MSCs was detected, while

INVITE micelles protected them from this effect. Moreover, MSCs loaded with INVITE MC are able to
release the entrapped drug. This study strongly supports the feasibility of the carrier-in-carrier approach
for the therapy of selected diseases, i.e., this innovative drug delivery system will be proposed for the
treatment of the amyotrophic lateral sclerosis (ALS).

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