Evolving new-age strategies to transport therapeutics across the blood-brain-barrier

Choudhari, Manisha; Hejmady, Siddhanth; Saha, Ranendra Narayan; Damle, Shantanu; Singhvi, Gautam; Alexander, Amit; Kesharwani, Prashant; Dubey, Sunil Kumar

doi:10.1016/j.ijpharm.2021.120351

Cited by 39 publications

(18 citation statements)

References 159 publications

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“…Despite paracellular transport over a compromised BBB showing promise in animal models, the alternative method of crossing the BBB through receptor-mediated transcytosis has recently shown greater promise. These methods are divided into three categories: employing a viral vector that naturally crosses the BBB (usually, AAV9 [ 94 ]); altering vectors to attach to a particular transcellular transport receptor; and changing vectors to attach to a specific transcellular transport receptor [ 95 ]. Guided evolution was used to generate a vector that binds with an appropriate receptor despite specifying which one.…”

Section: Advances In Drug Delivery Across the Blood–brain Barriermentioning

confidence: 99%

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

et al. 2022

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The blood–brain barrier (BBB) has shown to be a significant obstacle to brain medication delivery. The BBB in a healthy brain is a diffusion barrier that prevents most substances from passing from the blood to the brain; only tiny molecules can pass across the BBB. The BBB is disturbed in specific pathological illnesses such as stroke, diabetes, seizures, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. The goal of this study is to offer a general overview of current brain medication delivery techniques and associated topics from the last five years. It is anticipated that this review will stimulate readers to look into new ways to deliver medications to the brain. Following an introduction of the construction and function of the BBB in both healthy and pathological conditions, this review revisits certain contested questions, such as whether nanoparticles may cross the BBB on their own and if medications are selectively delivered to the brain by deliberately targeted nanoparticles. Current non-nanoparticle options are also discussed, including drug delivery via the permeable BBB under pathological circumstances and the use of non-invasive approaches to improve brain medication absorption.

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Section: Advances In Drug Delivery Across the Blood–brain Barriermentioning

confidence: 99%

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

et al. 2022

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“…To improve BBB crossing, one antibody-binding site would recognise an endogenous BBB receptor and therefore acting as a Trojan horse, while the other site would recognise a therapeutic target inside the CNS. The ideal target receptor for this receptor-mediated transcytosis across the BBB needs to be highly and specifically expressed on brain endothelial cells ( Choudhari et al, 2021 ; Pardridge, 2017 ). Several receptors for receptor-mediated transcytosis across the BBB have been considered so far as antigen for bispecific antibodies, such as the insulin receptor, LRP1 and LRP2 CD98hc ( Zuchero et al, 2016 ), but the transferrin receptor remains the most widely targeted delivery system ( Tashima, 2020 ) with promising results in Alzheimer’s disease models (Y. J.…”

Section: Fcrn and Cellular Barriersmentioning

confidence: 99%

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

Ojaimi

Blin

Lamamy

et al. 2022

Pharmacology & Therapeutics

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Antibody-based therapeutics have become a major class of therapeutics with over 120 recombinant antibodies approved or under review in the EU or US. This therapeutic class has experienced a remarkable expansion with an expected acceleration in 2021–2022 due to the extraordinary global response to SARS-CoV2 pandemic and the public disclosure of over a hundred anti-SARS-CoV2 antibodies. Mainly delivered intravenously, alternative delivery routes have emerged to improve antibody therapeutic index and patient comfort. A major hurdle for antibody delivery and efficacy as well as the development of alternative administration routes, is to understand the different natural and pathological barriers that antibodies face as soon as they enter the body up to the moment they bind to their target antigen. In this review, we discuss the well-known and more under-investigated extracellular and cellular barriers faced by antibodies. We also discuss some of the strategies developed in the recent years to overcome these barriers and increase antibody delivery to its site of action. A better understanding of the biological barriers that antibodies have to face will allow the optimization of antibody delivery near its target. This opens the way to the development of improved therapy with less systemic side effects and increased patients’ adherence to the treatment.

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“…Earlier reports showed the expression of Tf receptor (TfR) in all nucleated cells and the BBB and overexpression in a variety of tumors (Nabi et al, 2018a). TfR is overexpressed in brain neurons, capillary endothelium cells, and choroid plexuses (Sundaram et al, 2009;Choudhari et al, 2021). Tf is a glycoprotein that binds to the iron in the blood and delivers it to the brain via TfR present on the BBB (Sharma et al, 2016a;Choudhari et al, 2021).…”

Section: Transferrin Receptorsmentioning

confidence: 99%

“…TfR is overexpressed in brain neurons, capillary endothelium cells, and choroid plexuses (Sundaram et al, 2009;Choudhari et al, 2021). Tf is a glycoprotein that binds to the iron in the blood and delivers it to the brain via TfR present on the BBB (Sharma et al, 2016a;Choudhari et al, 2021). The transport of Holo-Tf from blood to the brain and apo-Tf from the brain to blood is mediated by the TfR (Liu et al, 2013).…”

Section: Transferrin Receptorsmentioning

confidence: 99%

“…The insulin receptor is abundantly present in the brain (hypothalamus, hippocampus, cerebral cortex, and olfactory bulb). In CNS, these receptors have effective action in neuronal survival, homeostasis, and reproductive endocrinology (Choudhari et al, 2021). Insulin is an endogenous protein that is transported via receptor-mediated transcytosis to the brain and specifically acts on insulin receptors (Cano et al, 2020).…”

Section: Transferrin Receptorsmentioning

confidence: 99%

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An Insight to Brain Targeting Utilizing Polymeric Nanoparticles: Effective Treatment Modalities for Neurological Disorders and Brain Tumor

Annu

Ali

Qamar

et al. 2022

Front. Bioeng. Biotechnol.

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The delivery of therapeutic molecules to the brain remains an unsolved problem to the researchers due to the existence of the blood–brain barrier (BBB), which halts the entry of unwanted substances to the brain. Central nervous system (CNS) disorders, mainly Parkinson’s disease, Alzheimer’s disease, schizophrenia, brain tumors, and stroke, are highly prevalent globally and are a growing concern for researchers due to restricting the delivery of pharmaceutical drugs to the brain. So effective treatment modalities are essential to combat the growing epidemic of CNS diseases. Recently, the growing attention in the field of nanotechnology has gained the faith of researchers for the delivery of therapeutics to the brain by targeting them to the specific target site. Polymeric nanoparticles (PNPs) emerge out to be an instrumental approach in drug targeting to the brain by overcoming the physiological barrier, biomedical barrier, and BBB. Preclinical discovery has shown the tremendous potential and versatility of PNPs in encapsulating several drugs and their targeting to the deepest regions of the brain, thus improving therapeutic intervention of CNS disorders. The current review will summarize advances in the development of PNPs for targeting therapeutics to the brain and the functional and molecular effects obtained in the preclinical model of most common CNS diseases. The advancement of PNPs in clinical practice and their prospect in brain targeting will also be discussed briefly.

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Evolving new-age strategies to transport therapeutics across the blood-brain-barrier

Cited by 39 publications

References 159 publications

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

Therapeutic antibodies – natural and pathological barriers and strategies to overcome them

An Insight to Brain Targeting Utilizing Polymeric Nanoparticles: Effective Treatment Modalities for Neurological Disorders and Brain Tumor

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