Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model

Author:

Perumal Venkatesan1ORCID,Ravula Arun Reddy1ORCID,Agas Agnieszka1ORCID,Gosain Aakaash1,Aravind Aswati1,Sivakumar Ponnurengam Malliappan23,I Shanmuga Sundari4,Sambath Karthik5ORCID,Vijayaraghavalu Sivakumar6ORCID,Chandra Namas1

Affiliation:

1. Center for Injury Biomechanics, Materials and Medicine, Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA

2. Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam

3. School of Medicine and Pharmacy, Duy Tan University, Da Nang 550000, Vietnam

4. Computational Biology Special Lab, Department of Biotechnology, Bannari Amman Institute of Technology, Sathyamangalam 638401, India

5. Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, 323 Martin Luther King Jr. Blvd., Newark, NJ 07102, USA

6. Department of Life Sciences (Zoology), Manipur University, Imphal 795003, India

Abstract

Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline’s neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood–brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.

Funder

faculty seed grant (FSG), NJIT

Publisher

MDPI AG

Subject

General Neuroscience

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