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Peer-reviewedCC BY-NC-ND 4.0BioMedical Engineering OnLine

Nanomedicine strategies for overcoming the blood–brain barrier in central nervous system drug delivery: mechanisms, advances, and challenges

  • Mukul Pratap Singh1
  • Ananda Kumar Chettupalli2
  • Sarad Pawar Naik Bukke3,4
  • Bharath Kumar Mamilla Mugaiahgari5
  • Pavani Uppu6
  • Priyanshu Pathak1
  • Bayapa Reddy Narapureddy7
7 affiliations
  1. 1Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh 203201 India
  2. 2Department of Pharmaceutical Technology, School of Health and Medical Sciences, Adamas Knowledge City, Adamas University, Barasat-Barrackpore, District-24 Parganas (North), Kolkata, 700126 West Bengal India
  3. 3Department of Pharmaceutics and Pharmaceutical Technology, Kampala International University, Western Campus, P.O. Box 71, Ishaka-Bushenyi, Uganda
  4. 4Department of Pharmacy – Faculty of Health Sciences, Victoria University, Victoria Towers, 1–13 Jinja Road, Kampala, Uganda
  5. 5Department of Emergency Medical Services, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia
  6. 6Department of Pharmaceutics, Nethaji Institute of Pharmaceutical Sciences. Somidi, Kazipet, Warangal, Telangana 506003 India
  7. 7Department of Public Health, College of Applied Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia
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Abstract

Central nervous system (CNS) disorders remain one of the most significant challenges in medicine given the restrictive properties of the blood–brain barrier (BBB), which substantially reduces the delivery of most therapeutics to penetrate the brain. Although there has been considerable progress in the generation of support neuroactive substances, approximately 98% of possible CNS medicines never get to effective milligram proofs in the brain, mostly due to exclusion from BBB. This research offers an in-depth and analytical assessment of approaches utilizing nanomedicine aimed at addressing the limitations of the blood–brain barrier (BBB) and improving the delivery of drugs to the brain. It thoroughly explores the structural and functional properties of the BBB, identifies the major obstacles hindering molecular movement, and investigates the cellular and molecular processes that regulate the movement of nanoparticles. Significant focus is given to various nanocarrier platforms, encompassing lipid-based systems (such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles, micelles, dendrimers, nanogels, nanoemulsions, exosomes, carbon nanotubes, and metallic nanoparticles. These platforms are particularly noted for their important functions in improving drug stability, bioavailability, controlled release, and precision targeting within the central nervous system. Furthermore, recent developments in innovative technologies, including nanofiber scaffolds and multidimensional (3D-6D) printing methods for neurological uses, are also discussed. The paper also analyses translational hurdles, safety issues, and toxicity factors that persistently obstruct the clinical application of nanomedicine-based CNS therapeutics. This paper highlights the revolutionary potential of nanotechnology in brain drug delivery and offers insights into future strategies for the rational design of safe and effective nanocarriers to meet unmet demands in CNS disease therapy.

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Cite

BibTeXRIS
BibTeX
@article{singh2026nanomedicine,
  title = {{Nanomedicine strategies for overcoming the blood–brain barrier in central nervous system drug delivery: mechanisms, advances, and challenges}},
  author = {Mukul Pratap Singh and Ananda Kumar Chettupalli and Sarad Pawar Naik Bukke and Bharath Kumar Mamilla Mugaiahgari and Pavani Uppu and Priyanshu Pathak and Bayapa Reddy Narapureddy},
  journal = {BioMedical Engineering OnLine},
  year = {2026},
  month = may,
  doi = {10.1186/s12938-026-01582-x},
  url = {https://doi.org/10.1186/s12938-026-01582-x},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Nanomedicine strategies for overcoming the blood–brain barrier in central nervous system drug delivery: mechanisms, advances, and challenges
AU  - Mukul Pratap Singh
AU  - Ananda Kumar Chettupalli
AU  - Sarad Pawar Naik Bukke
AU  - Bharath Kumar Mamilla Mugaiahgari
AU  - Pavani Uppu
AU  - Priyanshu Pathak
AU  - Bayapa Reddy Narapureddy
PY  - 2026
DA  - 2026/05/21
JO  - BioMedical Engineering OnLine
DO  - 10.1186/s12938-026-01582-x
UR  - https://doi.org/10.1186/s12938-026-01582-x
AB  - Central nervous system (CNS) disorders remain one of the most significant challenges in medicine given the restrictive properties of the blood–brain barrier (BBB), which substantially reduces the delivery of most therapeutics to penetrate the brain. Although there has been considerable progress in the generation of support neuroactive substances, approximately 98% of possible CNS medicines never get to effective milligram proofs in the brain, mostly due to exclusion from BBB. This research offers an in-depth and analytical assessment of approaches utilizing nanomedicine aimed at addressing the limitations of the blood–brain barrier (BBB) and improving the delivery of drugs to the brain. It thoroughly explores the structural and functional properties of the BBB, identifies the major obstacles hindering molecular movement, and investigates the cellular and molecular processes that regulate the movement of nanoparticles. Significant focus is given to various nanocarrier platforms, encompassing lipid-based systems (such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles, micelles, dendrimers, nanogels, nanoemulsions, exosomes, carbon nanotubes, and metallic nanoparticles. These platforms are particularly noted for their important functions in improving drug stability, bioavailability, controlled release, and precision targeting within the central nervous system. Furthermore, recent developments in innovative technologies, including nanofiber scaffolds and multidimensional (3D-6D) printing methods for neurological uses, are also discussed. The paper also analyses translational hurdles, safety issues, and toxicity factors that persistently obstruct the clinical application of nanomedicine-based CNS therapeutics. This paper highlights the revolutionary potential of nanotechnology in brain drug delivery and offers insights into future strategies for the rational design of safe and effective nanocarriers to meet unmet demands in CNS disease therapy.
SN  - 1475-925X
ER  -