Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Perumal, Venkatesan; Ravula, Arun Reddy; Shao, Ningning; Chandra, Namas

doi:10.1016/j.joto.2022.09.002

Cited by 5 publications

(3 citation statements)

References 83 publications

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“…Blast injury: Rats were subjected to a single blast wave as described previously in ( , accessed on 19 February 2023) [ 33 , 61 , 76 , 77 ]. Rats were then strapped securely to an aluminum plate using a cotton cloth wrapped around the body and placed horizontally inside a 6 m long and 9 in.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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“…Blast injury: The rats were subjected to a single blast wave at the Center of Injury Biomechanics, Materials, and Medicine (New Jersey Institute of Technology, Newark, NJ, USA) in a 9 inch square cross-section shock tube, as described previously [43][44][45][46]. The principal animals used in this study were rats, with 4-5 animal in each experimental group (power value of 0.8, α = 0.05) based on a power analysis.…”

Section: Transwell Migration Assaymentioning

confidence: 99%

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

Perumal

Ravula

Agas

et al. 2023

Micro

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide, affecting over 10 million people annually, with an estimated cost of $76.5 billion. Although apocynin freely transverses the blood–brain barrier (BBB), its application is limited due to its rapid elimination, low terminal half-life (t1/2 = 6.7 min), narrow dose–response relationship, and cytotoxicity, thereby requiring repeated dosages. With this study, we aimed to develop transferrin-functionalized nanoparticles encapsulating apocynin to treat neuroinflammation for targeted drug delivery to sites of brain injury. As a preliminary approach, we endeavored to optimize the formulation parameters of apocynin-loaded albumin nanoparticles prepared through the desolvation method. The nanoparticles were characterized for their size, polydispersity, surface charge, drug loading and in vitro drug release. In this study, we also investigated the anti-inflammatory and neuroprotective effects of free apocynin and nanoparticle-loaded apocynin in neuronal cells. We show that the developed formulation displayed monodispersed, nanosized particles with higher entrapment efficiency, loading, stability, and sustained release profiles. The permeability of the nanoparticles across HBMECs reached the maximum at 67%. The in vivo evaluation revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles after I.V. administration. In vivo nanoparticle localization studies using a blast TBI (bTBI) model and confocal fluorescence microscopy have shown that tf-apoANPs are successful in delivering relatively high amounts of nanoparticles to the brain parenchyma and glial cells compared to non-targeted nanoparticles. We also establish that targeted nanoparticles accumulate in the brain. In conclusion, tf-apoANPs are efficacious carriers for targeted delivery across the blood–brain barrier to potentially treat neuroinflammation in brain injury and other diseases.

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“…Specific nanoparticle types, their payloads, the model studied, and the outcomes are listed in Table 1 . The majority of astrocyte research to date has employed either polymer NPs or dendrimers to deliver APIs ( Newland et al, 2014 ; Serramia et al, 2015 ; Lozic et al, 2016 ; Kong et al, 2017 ; Chowdhury et al, 2018 ; Surnar et al, 2018 ; Holmkvist et al, 2020 ; Proulx et al, 2020 ; Vismara et al, 2020 ; Wang et al, 2020 ; Clementino A. et al, 2021 ; Gu et al, 2022 ; Huang et al, 2022 ; Narsineni et al, 2023 ; Perumal et al, 2023 ; Sabourian et al, 2023 ; Zhang F. et al, 2023 ). API payloads range from small molecule drugs to proteins, plasmid DNA, and siRNA ( Montenegro et al, 2011 ; Kannan et al, 2012 ; Chen and Foldvari, 2016 ; Tickle and Chari, 2019 ; Porkolab et al, 2020 ; Gu et al, 2022 ).…”

Section: Nanomaterials For Api Delivery To Cns Gliamentioning

confidence: 99%

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Saksena,

Hamilton,

Gilbert

et al. 2023

Front. Cell. Neurosci.

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Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood–brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective. Novel nanomaterials are being developed to deliver APIs into the CNS to modulate glial responses and improve outcomes in injury and disease. Nanomaterials are attractive options as therapies for central nervous system protection and repair in degenerative disorders and traumatic injury due to their intrinsic capabilities in API delivery. Nanomaterials can improve API accumulation in the CNS by increasing permeation through the BBB of systemically delivered APIs, extending the timeline of API release, and interacting biophysically with CNS cell populations due to their mechanical properties and nanoscale architectures. In this review, we present the recent advances in the fields of both locally implanted nanomaterials and systemically administered nanoparticles developed for the delivery of APIs to the CNS that modulate glial activity as a strategy to improve outcomes in traumatic injury and disease. We identify current research gaps and discuss potential developments in the field that will continue to translate the use of glia-targeting nanomaterials to the clinic.

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Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Cited by 5 publications

References 83 publications

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

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

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

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