title: Mesenchymal stromal cells loading curcumin-INVITE-micelles: a drug delivery system for neurodegenerative diseases.
abstract: 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).
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: giuseppe.tripodo@unipv.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tripodo
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: theodora.chlapanidas@unipv.it.
authors.forename: Theodora
authors.initials: T
authors.lastname: Chlapanidas
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: sara.perteghella@unipv.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Perteghella
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: barbara.vigani@unipv.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vigani
authors.affiliation: Department of Pharmacy, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: delia.mandracchia@uniba.it.
authors.forename: Delia
authors.initials: D
authors.lastname: Mandracchia
authors.affiliation: Department of Pharmacy, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: adriana.trapani@uniba.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; Struttura Semplice Tissue Therapy, Niguarda Hospital, Piazza dell'Ospedale Maggiore 3, 20162 Milan, Italy. Electronic address: marta.galuzzi@ospedaleniguarda.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Galuzzi
authors.affiliation: Struttura Semplice Tissue Therapy, Niguarda Hospital, Piazza dell'Ospedale Maggiore 3, 20162 Milan, Italy. Electronic address: martacecilia.tosca@ospedaleniguarda.it.
authors.forename: Marta Cecilia
authors.initials: MC
authors.lastname: Tosca
authors.affiliation: Struttura Semplice Tissue Therapy, Niguarda Hospital, Piazza dell'Ospedale Maggiore 3, 20162 Milan, Italy. Electronic address: barbara.antonioli@ospedaleniguarda.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Antonioli
authors.affiliation: Neurosurgical Department, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy. Electronic address: p.gaetani@smatteo.pv.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gaetani
authors.affiliation: Struttura Semplice Tissue Therapy, Niguarda Hospital, Piazza dell'Ospedale Maggiore 3, 20162 Milan, Italy. Electronic address: mario.marazzi@ospedaleniguarda.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Marazzi
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: marina.torre@unipv.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Torre
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000601:surgery; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D065546:Drug Liberation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007444:Inulin / Q000737:chemistry; D007700:Kinetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008823:Micelles; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D061251:Primary Cell Culture; D014810:Vitamin E / Q000737:chemistry; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D008823:Micelles; D018696:Neuroprotective Agents; D014810:Vitamin E; D007444:Inulin; D024502:alpha-Tocopherol; D003474:Curcumin
keywords: Amyotrophic lateral sclerosis (ALS); Curcumin; Inulin; Mesenchymal stromal cells; Vitamin E