Dendrimers

Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.

Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.

Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood-brain barrier (BBB) impedes the permeation and access of most drugs to central nervous system (CNS) and that many neurological diseases remain undertreated. Therefore, a number of nanocarriers have been designed over the past few decades to deliver drugs to the brain. Among these nanomaterials, dendrimers have procured an enormous attention from scholars because of their nanoscale uniform size, ease of multi-functionalization, and available internal cavities. As hyper-branched 3D macromolecules, dendrimers can be maneuvered to transport diverse therapeutic agents, incorporating small molecules, peptides, and genes; diminishing their cytotoxicity; and improving their efficacy. Herein, the present review will give exhaustive details of extensive researches in the field of dendrimer-based vehicles to deliver drugs through the BBB in a secure and effectual manner. It is also a souvenir in commemorating Donald A. Tomalia on his 80th birthday.

Employing messenger RNA (mRNA) for protein production in the liver or for vaccine purposes is a promising therapeutic approach. However, unlocking mRNA's full therapeutic potential requires systemic delivery platform technology with controllable biodistribution features. Apolipoprotein nanoparticles (aNP) containing monovalent ionizable cationic lipids have been shown to functionally deliver mRNA to myeloid progenitor cells in the bone marrow after intravenous administration. Here, the development of polyvalent ionizable cationic dendrimers is reported for incorporation in aNPs to enable efficient mRNA complexation and functional delivery. A library of dendrimers is first rationally designed with diverse hydrophobic core units, a number of branching units, and functionalized terminal units. Upon incorporation, eleven distinct dendrimer-based aNP-mRNA formulations are screened and characterized in vitro for their properties. Based on the screening outcome, four formulations are selected and evaluated their ability to induce functional gene expression in vivo. The results indicate that the lead polyvalent dendrimer-based aNP formulation outperformed formulations containing a clinically approved ionizable cationic lipid regarding gene expression in hematopoietic stem and progenitor cells in the bone marrow after intravenous administration.