"Combo" Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury.
Marzia MorettiRiccardo CaraffiLuca LorenziniIlaria OttonelliMichele SanniaGiuseppe AlastraVito Antonio BaldassarroAlessandro GiulianiJason Thomas DuskeyMaura CescattiBarbara RuoziLuigi AloeMaria Angela VandelliLuciana GiardinoGiovanni TosiLaura CalzàPublished in: Cells (2023)
Spinal cord injury (SCI) is characterized by a cascade of events that lead to sensory and motor disabilities. To date, this condition is irreversible, and no cure exists. To improve myelin repair and limit secondary degeneration, we developed a multitherapy based on nanomedicines (NMeds) loaded with the promyelinating agent triiodothyronine (T3), used in combination with systemic ibuprofen and mouse nerve growth factor (mNGF). Poly-L-lactic-co-glycolic acid (PLGA) NMeds were optimized and loaded with T3 to promote sustained release. In vitro experiments confirmed the efficacy of T3-NMeds to differentiate oligodendrocyte precursor cells. In vivo rat experiments were performed in contusion SCI to explore the NMed biodistribution and efficacy of combo drugs at short- and long-term post-lesion. A strong anti-inflammatory effect was observed in the short term with a reduction of type M1 microglia and glutamate levels, but with a subsequent increase of TREM2. In the long term, an improvement of myelination in NG2-IR, an increase in MBP content, and a reduction of the demyelination area were observed. These data demonstrated that NMeds can successfully be used to obtain more controlled local drug delivery and that this multiple treatment could be effective in improving the outcome of SCIs.
Keyphrases
- spinal cord injury
- drug delivery
- growth factor
- spinal cord
- neuropathic pain
- cancer therapy
- oxidative stress
- anti inflammatory
- induced apoptosis
- drug release
- cell cycle arrest
- electronic health record
- white matter
- signaling pathway
- inflammatory response
- machine learning
- stem cells
- wound healing
- drug induced
- bone marrow
- pet imaging
- artificial intelligence
- cell death
- postoperative pain