Table 2.
Dendrimers with intrinsic anti-inflammatory activity.
| Modification | Disease Models | Other Main Features | Reference |
|---|---|---|---|
| Poly(amidoamine) (PAMAM)-BASED Dendrimers | |||
| Surface-modified anionic G4.5-COOH and neutral G5-OH. | Mouse model of acute pancreatitis | Inhibition of macrophage infiltration and suppression of pro-inflammatory cytokine expression. | [148] |
| PAMAM or poly(ethylenimine) dendrimers immobilized onto PSMA/polystyrene microfiber meshes, generating nucleic acid-binding polymers. | Human cancer and mouse macrophage cell lines | Inhibition of DAMP-mediated TLR stimulation and thrombosis by scavenging exDNA and HMGB1. Attenuation of inflammatory responses and coagulation induced by traumatic injury. | [149] |
| Simple surface modification of PAMAM dendrimers with -NH2, -OH, and -COOH. | Rat models of inflammation | The first study on intrinsic anti-inflammatory activity of PAMAM dendrimers. | [79] |
| Polyethylene Glycol (PEG)-Based Dendrimers | |||
| Highly dense surface hydroxyl terminals. | Models: Rabbit, cerebral palsy; Murine, glioblastoma; rat, age-related macular degeneration | Ability to cross CNS barriers, including BBB, blood–retinal barrier (BRB), and blood–brain-tumor barrier (BBTB). Selectively targets activated microglia/macrophages in CNS in vivo upon systemic administration. Intrinsic anti-oxidant and anti-inflammatory activities in vitro. | [147] |
| Polyglycerol-Based Dendrimers | |||
| Dendritic polyglycerols were either terminated with hydroxyl groups (dPG) or sulfate groups (dPGS). | Mouse primary cortical cultures; mouse model of microglial cell activation | dPGS alleviated LPS-induced microglia activation, reduction in LCN-2 production mainly in astrocytes. dPGS directly bound to IL-6 and LCN-2, attenuating astrocyte stimulation. | [31] |
| G3.5 dPGS | Organotypic hippocampal slice cultures | dPGS treatment in Alzheimer disease models prevents Aβ fibril formation by directly interacting with the Aβ42 peptide, and attenuating Aβ-induced neuroinflammation. | [22] |
| Sulfated polyglycerols (dPGS) and non-sulfated analogs (dPG). | Organotypic hippocampal slice cultures | dPGS reduces pro-inflammatory cytokine production from M1 microglia phenotype, and normalizes LPS-induced morphology of the hippocampal dendritic spines. | [32] |
| Anionic dPGS moieties interact with the ligand binding sites of P- and L-selectin through electrostatic interactions. | Mouse model of contact dermatitis and complement activation | The first report about the anti-inflammatory activity of dPGS. | [80] |
| Phosphorus-Based Dendrimers | |||
| Fluorescent phosphorus dendrimers. | Murine macrophages (M1 and M2 phenotypes) | Generation of the phenotype-dependent blue spectral shift upon macrophage polarization, potential use of biosensor identifying macrophages and their phenotypes. | [150] |
| Polyphosphorhydrazone (PPH)-Based Dendrimers | |||
| Azabisphosphonated (ABP) surface modification imparts anti-inflammatory activity to the dendrimer. | Mouse model of experimental autoimmune encephalomyelitis and arthritis. Human peripheral blood mononuclear cell line. | Attenuation of the pathological symptoms and mediation of the inflammatory response through regulating immune cells and decreased cytokine release. | [137,138,151] |