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Recent trends of bioconjugated nanomedicines through nose-to-brain delivery for neurological disorders

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Abstract

The global burden of neurological disorders has been increasing day by day which calls for immediate attention to the solutions. Novel drug delivery systems are one of the alternatives that we count on to counteract these disorders. As the blood–brain barrier creates a significant hindrance to the delivery of drugs across the endothelium lining of the brain, nose-to-brain delivery has been the favorite option to administer such drugs. In recent times, bioconjugation has been viewed as a rapidly growing area in the field of pharmaceuticals. The pharmaceutical industry and academic research are investing significantly in bioconjugated structures as an attractive and advantageous potential aid to nanoparticulate delivery systems, with all of its flexible benefits in terms of tailor grafting and custom design as well as overcoming the majority of their drawbacks. This review discusses drug delivery via the intranasal route and gives insight into bioconjugation systems for drug molecules, their chemistry, and benefits over other systems. Conjugation of drugs/macromolecules with peptides, carbohydrates, ligands, and nucleic acids has also been discussed in detail.

Graphical abstract

The figure represents few types of novel drug delivery systems and molecules that have been attempted by researchers for nose-to-brain delivery through nasal (mucosal) route for the effective management of epilepsy, Alzheimer’s disease, brain cancer, and other brain disorders.

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Abbreviations

AD:

Alzheimer’s disease

ADC:

Antibody-drug conjugate

BBB:

Blood-brain barrier

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DA:

Dopamine

DIC:

N,N′-Diisopropylcarbodiimide

DRG:

Delonix Regia Gum

DZ:

Donepezil

EDC:

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide

FBS:

Fetal bovine serum

FGFR:

Fibroblast growth factor receptor

HA:

Hyaluronic acid

HOAt:

1-Hydroxy-7-azabenzotriazole

HOBt:

1-Hydroxybenzotriazole

HOPy:

1-Hydroxy-2-pyridinone

HRP:

Horseradish peroxidase

LUMO:

Lowest unoccupied molecular orbital

MMP:

Matrix metalloproteinase

NHS:

N-Hydroxysuccinimide

NPs:

Nanoparticles

OECs:

Olfactory ensheathing cells

PAMAM:

Polyamidoamine

PD:

Parkinson’s disease

PDZ:

PAMAM 4.0 G dendrimer

PEG:

Polyethylene glycol

PLA:

Polylactic acid

PLGA:

Polylactic-co-glycolic acid

PM:

Polymeric micelles

PTX:

Paclitaxel

SNF:

Simulated nasal fluid

TMP:

Tetramethylpyrazine

WGA:

Wheat germ agglutinin

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Acknowledgements

The authors are grateful to the National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, and highly acknowledged to former Director, Prof. Kiran Kalia for the support.

Funding

BS and GJ would like to acknowledge the Department of Science and Technology (DST)-Science and Engineering Research Board (SERB) for providing the grant (file no. SRG/2020/001241).

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  1. Tejas Girish Agnihotri and Govinda Shivaji Jadhav contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India

    Tejas Girish Agnihotri & Aakanchha Jain

  2. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Palaj, Gandhinagar, 382355, Gujarat, India

    Govinda Shivaji Jadhav & Bichismita Sahu

Authors
  1. Tejas Girish Agnihotri
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  2. Govinda Shivaji Jadhav
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  3. Bichismita Sahu
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  4. Aakanchha Jain
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Contributions

TA and GJ drafted the manuscript; BS contributed in giving valuable suggestion for bioconjugation portion written.

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Correspondence to Aakanchha Jain.

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All the authors do hereby give their consent for publication of the work entitled “Recent Trends of Bioconjugated Nanomedicines through Nose-to-Brain Delivery for Neurological Disorders” in drug delivery and translational research.

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Articles drafting and selection criteria

The article proposed here has been drafted following the given steps: we searched PubMed, Science Direct, and SciFinder (1983–2021) with the search terms “nose-to-brain delivery,” “bioconjugation types and strategies,” “nanoparticles for the nose-to-brain delivery,” and “bioconjugated nanosystems.” We primarily selected articles from the last 10 years and also included older publications that are found to be establishing the foundation for the concepts outlined in the manuscript.

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Agnihotri, T.G., Jadhav, G.S., Sahu, B. et al. Recent trends of bioconjugated nanomedicines through nose-to-brain delivery for neurological disorders. Drug Deliv. and Transl. Res. 12, 3104–3120 (2022). https://doi.org/10.1007/s13346-022-01173-y

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  • DOI: https://doi.org/10.1007/s13346-022-01173-y

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