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Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma.

Publication ,  Journal Article
Saha, S; Yakati, V; Shankar, G; Jaggarapu, MMCS; Moku, G; Madhusudana, K; Banerjee, R; Ramkrishna, S; Srinivas, R; Chaudhuri, A
Published in: Journal of materials chemistry. B
May 2020

Combating brain tumors (glioblastoma multiforme or GBM) is a formidable challenge because of the existence of blood-brain barrier (BBB), a tight cellular junction that separates the central nervous system (CNS) and systemic circulation. Such a selectively permeable barrier prevents the entry of therapeutic molecules from blood circulation to brain parenchyma. Towards enhancing the efficacy of brain tumor-selective drug delivery without perturbing the BBB integrity, nanometric drug carriers are increasingly becoming an efficient therapeutic modality in preclinical studies. Psychostimulant drugs such as amphetamine and methylated amphetamine (METH) are known to penetrate the BBB. Still, little effort has been made to exploit them in nano-drug delivery, largely due to their toxicities. Herein, for the first time, we design, synthesize, and formulate three different β-amphetaminylated cationic lipid nanoparticles. We show that the β-amphetaminylated cationic lipid nanoparticles are nontoxic and can cross the BBB presumably through active transcytosis. The BBB penetrating ability also depends on the hydrophilic-hydrophobic balance of the lipids, with hexadecyl lipid (16-BACL) nanoparticle showing maximum accumulation in the brain. The lipid nanoparticle of 16-BACL can simultaneously encapsulate paclitaxel and PDL1-siRNA. The dual drug-loaded lipid nanoparticles showed apoptosis driven cellular cytotoxicity against GL261 cells and improved the overall survivability of orthotopic glioblastoma bearing mice compared to their non-targeting counterpart. The present work describes a new class of BBB-crossing lipid nanoparticles and delineates their therapeutic promise against glioblastoma.

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Published In

Journal of materials chemistry. B

DOI

EISSN

2050-7518

ISSN

2050-750X

Publication Date

May 2020

Volume

8

Issue

19

Start / End Page

4318 / 4330

Related Subject Headings

  • Tumor Cells, Cultured
  • Surface Properties
  • RNA, Small Interfering
  • Particle Size
  • Paclitaxel
  • Nanoparticles
  • Molecular Structure
  • Mice, Inbred C57BL
  • Mice
  • Lipids
 

Citation

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Saha, S., Yakati, V., Shankar, G., Jaggarapu, M. M. C. S., Moku, G., Madhusudana, K., … Chaudhuri, A. (2020). Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma. Journal of Materials Chemistry. B, 8(19), 4318–4330. https://doi.org/10.1039/c9tb02700a
Saha, Soumen, Venu Yakati, Gajji Shankar, Madan Mohan Chandra Sekhar Jaggarapu, Gopikrishna Moku, Kuncha Madhusudana, Rajkumar Banerjee, Sistla Ramkrishna, Ragampeta Srinivas, and Arabinda Chaudhuri. “Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma.Journal of Materials Chemistry. B 8, no. 19 (May 2020): 4318–30. https://doi.org/10.1039/c9tb02700a.
Saha S, Yakati V, Shankar G, Jaggarapu MMCS, Moku G, Madhusudana K, et al. Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma. Journal of materials chemistry B. 2020 May;8(19):4318–30.
Saha, Soumen, et al. “Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma.Journal of Materials Chemistry. B, vol. 8, no. 19, May 2020, pp. 4318–30. Epmc, doi:10.1039/c9tb02700a.
Saha S, Yakati V, Shankar G, Jaggarapu MMCS, Moku G, Madhusudana K, Banerjee R, Ramkrishna S, Srinivas R, Chaudhuri A. Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma. Journal of materials chemistry B. 2020 May;8(19):4318–4330.
Journal cover image

Published In

Journal of materials chemistry. B

DOI

EISSN

2050-7518

ISSN

2050-750X

Publication Date

May 2020

Volume

8

Issue

19

Start / End Page

4318 / 4330

Related Subject Headings

  • Tumor Cells, Cultured
  • Surface Properties
  • RNA, Small Interfering
  • Particle Size
  • Paclitaxel
  • Nanoparticles
  • Molecular Structure
  • Mice, Inbred C57BL
  • Mice
  • Lipids