SARS-CoV-2: The Road Less Traveled—From the Respiratory Mucosa to the Brain

Anoop, U R; Verma, Kavita; Rajendran, Rahini; Chidambaram, Subbulakshmi

doi:10.1021/acsomega.1c00030

Cited by 8 publications

(5 citation statements)

References 26 publications

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“…However, nasal drops applied topically on the nasal mucosa of the mouse showed the distribution of the drug in the brain only at the midline. The study also showed that the drug was transported to both eyes, and slightly more fluorescence was detected in the contralateral eye …”

Section: Results and Discussionmentioning

confidence: 80%

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Rajendran,

Arunachalam,

Chidambaram

et al. 2023

ACS Chem. Neurosci.

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Protein drugs are used for treating many diseases of the eye and the brain. The formidable blood neural barriers prevent the delivery of these drugs into the eye and the brain. Hence, there is a need for a protein drug delivery system to deliver large proteins across blood-neural barriers. Low half-life, poor penetration of epithelial barriers, low stability, and immunogenicity limit the use of non-invasive systemic routes for delivering proteins. In this pre-clinical study, the efficacy of a new maxillofacial route for administering protein drugs using a novel drug delivery system is compared with systemic administration through intra-peritoneal injection and ocular administration through topical eye drops and subconjunctival and intravitreal injections. Bevacizumab and retinoschisin proteins were administered using the maxillofacial technique along with systemic and ocular routes in wild-type male C57BL/6J mice. Liquid chromatography with tandem mass spectrometry and western blot was used to detect bevacizumab in tissue samples. Furthermore, immunohistochemistry was performed to detect the presence and localization of bevacizumab and retinoschisin in the retina and brain. The maxillofacial route of delivery could target the brain including regions involved in the visual pathway and optic nerve. The maxillofacial technique and intravitreal injection were effective in delivering the drugs into the retina. A new concept based on the glymphatic pathway, cerebrospinal fluid drug distribution, and the crossover of ipsilateral optic nerve fibers at optic chiasma is proposed to explain the presence of the drug in contralateral eye following maxillofacial administration and intravitreal injection.

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Section: Results and Discussionmentioning

confidence: 80%

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Rajendran,

Arunachalam,

Chidambaram

et al. 2023

ACS Chem. Neurosci.

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“…The study also showed that the drug was transported to the eyes. The maxillofacial route showed slightly more fluorescence in the contralateral eye 36 .…”

Section: Discussionmentioning

confidence: 90%

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Rajendran

Chidambaram

Srikanth

et al. 2022

Preprint

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The blood neural barriers are formidable barriers that prevent delivery of drugs into the eye and the brain. Currently, large biologics are used for treating many diseases of the eye and the brain. But the blood retinal barrier and the blood brain barrier prevent entry of these useful drugs into the eye and the brain respectively. Hence, there is a need for a drug delivery technique to bypass these natural barriers. Bevacizumab (Avastin) is a full length humanized monoclonal antibody with a molecular weight of 149kda. It binds to circulating vascular endothelial growth factor A and prevents interaction with vascular endothelial growth receptors. This results in blocking endothelial response and tumor vascularization. Bevacizumab is used to prevent choroidal neovascularization in age related macular degeneration and to prevent retinal neovascularization in diabetic retinopathy. It is also used for treating certain types of brain cancer. But it crosses neither the blood retinal barrier nor the blood brain barrier. This in vivo mouse study assessed the delivery of a commercial formulation of bevacizumab into the retina of mice using different ocular techniques like topical drops, subconjunctival injection, intravitreal injection and a novel maxillofacial technique. The objective was to assess whether the novel maxillofacial drug delivery technique could deliver drugs into the retina and to compare the efficacy of the maxillofacial technique with the mentioned ocular techniques. The distribution of bevacizumab was further compared with retinoschisin which is a small protein with a molecular weight of 24kda. Intravitreal injection and maxillofacial technique were effective in delivering drugs into the retina. In addition, the maxillofacial technique could target the brain including regions involved in the visual pathway and the optic nerve. The glymphatic pathway could also be targeted for drug delivery. Drug was also detected in the contralateral optic nerve and retina. Based on our study findings, we propose a new concept to explain the presence of the drug in the contralateral eye. We propose that after maxillofacial drug delivery, early distribution of the drug can occur in the CSF at the optic chiasma from the brain via the glymphatic system. In the case of the intravitreal injection, the drug from the experimental eye may be cleared through the glymphatic pathway of the ipsilateral optic nerve into the CSF surrounding the nerve. The crossover of the ipsilateral optic nerve fibers at the optic chiasma can result in further distribution of the drug in the CSF at the optic chiasma. From the region of the optic chiasma, the drug can distribute into the CSF surrounding the contralateral optic nerve. The drug can be then distributed into the contralateral optic nerve through the glymphatic pathway and be delivered into the contralateral eye. The drug can be further cleared into the aqueous of the contralateral eye through the anterior clearance pathway.

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“…Patients will ultimately require device-assisted therapies to manage motor fluctuations [ 13 ]. Recently, in vivo animal studies have shown that drugs can be successfully delivered into the brain through the maxillofacial route via the paravascular, vascular, perineural, lymphatic, and glymphatic pathways [ 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

The Administration of Levodopa in a Patient With Parkinson’s Disease Using a Novel Maxillofacial Route: A First-in-Human Report

Thirunavukarasu,

Ramanan,

Suresh

et al. 2023

Cureus

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Parkinson's disease is characterized by the loss of nigrostriatal dopaminergic neurons in the brain. Dopamine cannot be administered systemically because it does not cross the blood-brain barrier. Oral levodopa remains the gold standard to date. Currently, for patients who show a poor response to oral levodopa and for those who cannot take it orally, the alternate routes available are inhalation and continuous administration via intestinal and subcutaneous routes. In this report, a novel maxillofacial route was used for the first time in the world to administer levodopa to a Parkinson's patient. Furthermore, the efficacy of maxillofacial administration was compared with the oral route of administration.

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SARS-CoV-2: The Road Less Traveled—From the Respiratory Mucosa to the Brain

Cited by 8 publications

References 26 publications

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

The Administration of Levodopa in a Patient With Parkinson’s Disease Using a Novel Maxillofacial Route: A First-in-Human Report

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