Category: Micro- and Nanotechnologies
Alzheimer’s disease (AD) is a chronic and progressive age related neurodegenerative disorder that begins with cognitive and memory impairments, accompanied with behavioral disturbances such as aggression, depression, hallucination, delusion, anger and eventually, progresses to dementia, physical impairment, and death. It is pathologically characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. The deposition of aggregated Aβ in the human brain is a major lesion in AD and is associated with a cascade of neuropathogenic events that includes brain neurodegeneration leading to cognitive and behavioral decline.
Therapeutic advancement of AD is complicated by the restrictive mechanisms imposed at BBB. The present day AD drug development effort is characterized by an imbalance wherein >99% of the drug development is devoted to CNS drug discovery and <1% is devoted to CNS drug delivery. Hence we are trying to develop nano carriers (carbon nanospheres) for targeting CNS.
Carbon nanospheres (CSPs) derived from glucose are biodegradable, non-toxic, intrinsically fluorescent, have the ability to deliver the drug molecules inside the nucleus and an economical alternative to presently used synthetic polymeric carriers. CSPs entry is chiefly GLUT1 and clathrin mediated ATP dependent endocytic process. Since glial cells containing GLUT1 are major components of the endothelial cells of mammalian brain and nose thereby CSPs have a potential application for specific targeting to the brain.
Hence we developed CSPs as carriers for targeting Donepezil (DZP), an acetylcholinesterase inhibitor, to the brain through intranasal route to avoid limitations associated with currently available forms, this helps to avoid systemic distribution of the drug by targeting to the brain.
Till date, we have finished and confirmed the compatibility of the DZP and excipients using FT-IR, DSC and XRD studies. Solubility and stability of DZP and carrier in simulated nasal fluid (SNF) was studied and results have shown the good amount of solubility and stability of the compounds. The analytical and bio-analytical method was developed for further studies.
DZP nanoformulations were prepared using various concentrations of DZP and carrier. From all the prepared batches, the optimized DZP-CSPs nanoformulation was selected based on entrapment efficiency and drug content. Optimized DZP-CSPs have shown the particle size of 275nm with zeta potential – 28mV and PDI <1. Optimized DZP-CSPs nanoformulation was further analyzed for morphological characterization using SEM and TEM and particles were found to be spherical. Toxicity assessment studies like erythrocyte toxicity, cytotoxicity assay, nasal ciliotoxicity studies were conducted on optimized nanoformulation (DZP-CSPs) to establish the safety profile. The results from the studies confirmed the safety of formulation. In-vivo pharmacodynamic studies were under way and giving very positive results as on date.
Keywords: Glucose nanoparticles, GLUT 1 receptors, status epilepticus, targeted delivery.
Satya Jakki– Research fellow, JSS University, UDHAGAMANDALAM, Tamil Nadu, India
UDHAGAMANDALAM, Tamil Nadu, India
Myself Ms. Satya Lavanya Jakki, from JSS College of pharmacy, JSS University, INDIA. My specific research and area of interest are development of various drug delivery systems (Gels, niosomes, proniosomes, transdermal systems, SLNs, NLCs etc.), novel natural polymers, nanotechnology, and targeted delivery to any part of the body up to cellular level.
I served as a research assistant for different contract based research works conducted in our institute for various pharmaceutical companies and have experience in teaching and guiding graduates and undergraduates. I have hands-on experience on different instruments (DSC, HPLC, IBOX SCIENTIA etc.) and techniques.
I have published my research findings in various peer-reviewed high impact factor journals (Journal Citation Reports - Thomson Reuters, 2017) serving as a first and corresponding author with a cumulative impact factor of 30. I am also a referee for various top scientific publishing groups like Elsevier, Taylor & Francis, and Bentham Science.