Category: Micro- and Nanotechnologies

1107-C - Targeting of glucose nanoparticles to brain through intranasal GLUT-1 receptor mediated delivery for the management of status epilepticus

Tuesday, February 6, 2018
2:00 PM - 3:00 PM

Status epilepticus (SE) is an emergency situation, where immediate and effective treatment is required in the least possible time as it is associated with neuronal damage, systemic complications, substantial morbidity and mortality depending on status type, duration, age, and etiology. In adults, patients older than 60 years had the highest risk of developing status epilepticus, with an incidence of 86 per 100,000 persons per year. According to WHO statistics, about 50 million people worldwide have epilepsy.

Presently available delivery systems have several drawbacks described as follows. The oral route is not accessible during seizures. In intravenous route, highly qualified, trained medical person is required for this procedure. Whereas the use of rectal route results in variable plasma levels and it is also socially embarrassing and difficult to administer during convulsions. Thus, an alternative fast-acting delivery route is needed.

Early termination of seizures, by initiating therapy as soon as possible, preferably at home, has been increasingly emphasized as a key to minimize the morbidity of these seizures. Therefore, a main goal of the treatment is the rapid termination of seizures to avoid the risk of permanent brain damage and mortality. The global response to this crisis has been inadequate. Hence, the best strategy is to develop novel drug delivery system in order to improve the efficacy, specificity, tolerability and therapeutic index of existing drugs.

Our research was focused on effective targeting of Lamotrigine (LTG) to the brain through Intranasal route (IN) using carbon nanospheres (CSPs) as carriers which help to reduce dose of drug, dose related side effects and terminating the seizures in the least possible time. Where drug can be easily administered by the surrounding people or caregivers and could dramatically improve the management of out-of-hospital seizures as well as the patient recovery.

FT-IR, DSC and XRD studies confirmed the compatibility of the drug and excipients. Prepared and optimized LTG-CSPs have shown the particle size of 250nm with zeta potential – 33mV and PDI <1. Surface morphology of LTG-CSPs was studied by SEM and TEM and found to be spherical. Entrapment efficiency was above >90 % with the drug content of around ~50 %. Further toxicity assessment studies confirmed the safety of the LTG-CSPs. In-vivo pharmacodynamic studies were under way and giving very positive results as on date.

The success and mechanism involved in LTG-CSPs crossing the blood brain barrier and reaching the brain cells maybe through the involvement of ATP dependent clathrin mediated endocytosis process (ATP-CEP). ATP-CEP plays a fundamental role in neurotransmission and signal transduction. The presence of higher levels of GLUT 1 receptors in nose and clathrin in the brain in comparison to other tissue also partly answers the more specificity of LTG-CSPs towards the brain.

Yasam Venkata Ramesh

Senior Research Fellow- Council of Scientific and Industrial Research (CSIR-SRF)
JSS University -
Udhagamandalam, Tamil Nadu, India

Greetings,
Myself Y. V. Ramesh, from JSS College of Pharmacy JSS University, INDIA.

My interdisciplinary area of research is the development of smart drug delivery systems, nanomedicine, nanotechnology, and targeted delivery to various diseases and disorders. I have also worked on various nano delivery systems (gels, patches, proniosomes, nanospheres) and carriers. As a part of the projects, I have hands-on experience on different instruments (DSC, HPLC, IBOX SCIENTIA etc.) and techniques.

My research findings were published in high impact factor journals (Journal Citation Reports - Thomson Reuters, 2017) serving as a first and corresponding author with a cumulative impact factor of 28.

Even I have received a fellowship from the government of INDIA (CSIR) for pursuing my doctoral research work.

Thank you very much for your time and consideration. I look forward to hearing from you soon.

Yours Sincerely,
Ramesh