dendrimer-drug conjugates by exploiting the selective, intrinsic, pathology-dependent, reactive microglia/macrophage uptake of dendrimers (tree-like nanoparticles) in over 40 models of central nervous system (CNS), ocular, and systemic disorder models across six species (mouse to primates and humans).
Rangaramanujam discussed the significance of nanotechnologies created for targeted drug delivery during his speech on the sidelines of the 12th edition of Bengaluru India Nano 2022. He explained in detail about the manipulation of reactive macrophages and its benefits. He said, “We show that appropriate manipulation of reactive glia/macrophages can have a dramatic impact on inflammation, oxidative stress, excitotoxicity, neurobehaviour and cognition in many models. These results not only provide unique insights into the role of macrophages on disease and repair, but also offer opportunities for developing potent systemic therapies for unmet needs, from childhood disorders such as cerebral palsy, to disorders affecting the elderly such as Covid-19, age-related macular degeneration (AMD), and Alzheimer’s Disease. The systemic therapeutic approach opens avenues for the technology to benefit patients across a broad economic spectrum”.
The researcher continued, saying that nanotechnology has emerged as a novel method for treating neurological problems. He said, “Therapeutic delivery to the brain faces several barriers to achieving sufficient drug concentrations at the diseased site. Nanotechnologies can be engineered to cross the blood-brain barrier and target specific cells”.
Dr Rangaramanujam demonstrated that a single intravenous dosage of dendrimer-drug conjugate delivered to newly born rabbit kits with cerebral palsy improves motor performance significantly and reduces neuroinflammation and oxidative damage by five days of age. He explained the experiment saying, “Tiny molecules such as N-acetyl-L-cysteine (NAC) were delivered directly to the brain. We gave a single dose of our nanomedicine and in five days the rabbit started hopping”.
Dr Rangaramanujam is currently on the mission of developing a Covid 19 anti-inflammatory medication, which is now through a phase II stage II study. He spoke about treating the inflammation. He said, “Severe inflammation is a major hallmark of Covid-19. The inflammation occurs not only in lungs but other parts of the body and could result in death. A single dose of our drug given intravenously to hospitalized Covid-19 patients treated systemic inflammation. We have seen 40 per cent improvement in survival among severe Covid-19 patients who got the drug. This nanomedicine targets macrophages affected by hyper-inflammation throughout the body”.
