TABLE 2.
Dendrimers for the inhibition of neuroinflammation and their mechanisms within in vitro and in vivo models.
| Dendrimers | Diameter (nm) | Biological model | Treatment | Dose | Mechanism and detected inflammatory cytokines | Toxicity | References |
|---|---|---|---|---|---|---|---|
| In vitro | |||||||
| D-mino | ∼8.4 nm | LPS-induced BV2 cells | 24 h co-culture | Concentration range of 50–500 µM | NO, TNF-a | 50–500 µM did not show cytotoxicity | Sharma et al. (2017) |
| PEGOL-60 | Not Given | LPS-induced BV2 cells | 24 h co-culture | 500 μg/ml | TNF-a, IL-4, IL-6, IL-10, and iNOS | >1,000 μg/ml did not show cytotoxicity for 24 h | Sharma et al. (2020a) |
| dPGS | 13.55 ± 0.14 nm | Primary neuroglia and organotypic hippocampal slice cultures exposed to Aβ-42 peptide | Pre-treated for 1 h | 1 M | Interfered with Aβ fibril formation and downregulation of LCN2 | Not Given | Maysinger et al. (2018) |
| D-Sino | 4.9 nm | LPS-induced RAW 264.7 cells | 8 h co-culture | 50 µg/ml, 100 µg/ml and 300 µg/ml | NF-κB pathway; TNF-α, IL-1β, CCL-3, IL-6, iNOS, and NO | >300 µg/ml did not show cytotoxicity, 500 µg/ml decreased cell viability to 82.7 ± 7.4% | Sharma et al. (2020b) |
| PAMAM-(COOH)46-(NAC)18 | Not Given | LPS-induced BV2 cells | Pre-treated for 3 h | 0.5 mM 2 mM, and 8 mM | ROS, NO, and TNF-α | 0.04–0.59 mM did not show cytotoxicity for 24 h | Wang et al. (2009) |
| PAMAM | ∼4 nm | Brain slice culture model from newborn rabbits exposed by endotoxin | 4 h co-culture | 5 ng in 10 μL of DPBS solution | More rapid diffusion and ability to “find” the less mobile activated microglia, increasing microglial uptake | Not Given | Zhang et al. (2016) |
| In vivo | |||||||
| ABP Dendrimer | Not Given | Mouse model of MOG35–55-induced autoimmune encephalomyelitis | Intravenous injection in different time in prophylactic and therapeutic groups | 10 mg/kg | IFN-γ, IL-17, and IL-10 | Did not induce immunosuppression or systemic toxicity in nonhuman primates | Hayder et al. (2015) |
| D-NAC | 5.4 nm | A rabbit model of cerebral palsy induced by maternal intrauterine endotoxin | Intravenous injection to newborn | 1 mg/kg, 10 mg/kg | NF-κB pathway; GSH and TNF-α | Nontoxic, nonimmunogenic, and are cleared intact through the kidneys | Kannan et al. (2012) |
| TPP-D-NAC | 7.5 ± 0.2 nm | A rabbit model of TBI induced by surgery | Intravenous injection at 6 h post-injury | 0.5 µg/ml, 5 µg/ml, and 50 µg/ml | Targeted delivery to mitochondria | Did not exhibit any reduction in cell viability at the doses tested | Sharma et al. (2018) |
| shCCL20-CCR6 | 100 nm | Mouse model of rTBI induced by surgery | Intranasal and intravenous administration after 3rd, 4th and 5th TBI | Not Given | IL-6 and CCL20 | Low doses did not show cytotoxicity | Mayilsamy et al. (2020) |