Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model
Document Type
Article
Publication Date
3-1-2023
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.
Identifier
85151447230 (Scopus)
Publication Title
Brain Sciences
External Full Text Location
https://doi.org/10.3390/brainsci13030402
e-ISSN
20763425
Issue
3
Volume
13
Fund Ref
Nanjing Institute of Technology
Recommended Citation
Perumal, Venkatesan; Ravula, Arun Reddy; Agas, Agnieszka; Gosain, Aakaash; Aravind, Aswati; Sivakumar, Ponnurengam Malliappan; I, Shanmuga Sundari; Sambath, Karthik; Vijayaraghavalu, Sivakumar; and Chandra, Namas, "Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model" (2023). Faculty Publications. 1883.
https://digitalcommons.njit.edu/fac_pubs/1883
