Development of Nanoparticles for Drug Delivery to Brain Tumor

The Effect of Surface Materials on Penetration Into Brain Tissue

Chenlu Lei, Pooya Davoodi, Wenbo Zhan, Pierce Kah-Hoe Chow, Chi-Hwa Wang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Surface-modified poly(d,l-lactic-co-glycolic acid) PLGA nanoparticles (NPs) were fabricated via nanoprecipitation for obtaining therapeutic concentration of paclitaxel (PTX) in brain tumor. The cellular uptake and cytotoxicity of NPs were evaluated on C6 glioma cells in vitro, and BALB/c mice were used to study the brain penetration and biodistribution upon intravenous administration. Results showed that by finely tuning nanoprecipitation parameters, PLGA NPs coated with surfactants with a size around 150 nm could provide a sustained release of PTX for >2 weeks. Surface coatings could increase cellular uptake efficiency when compared with noncoated NPs, and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) showed the most significant enhancement. The in vivo evaluation of TPGS-PLGA NPs showed amplified accumulation (>800% after 96 h) of PTX in the brain tissue when compared with bare NPs and Taxol®. Therefore, PLGA-NPs with PLGA-TPGS coating demonstrate a promising approach to efficiently transport PTX across blood-brain barrier in a safer manner, with the advantages of easy formulation, lower production cost, and higher encapsulation efficiency.
Original languageEnglish
Pages (from-to)1736-1745
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number5
Early online date12 Dec 2018
DOIs
Publication statusPublished - May 2019

Fingerprint

Brain Neoplasms
Nanoparticles
Paclitaxel
Brain
Pharmaceutical Preparations
glycolic acid
Blood-Brain Barrier
Surface-Active Agents
Glioma
Intravenous Administration
Milk
polylactic acid-polyglycolic acid copolymer
Costs and Cost Analysis
polyethylene glycol 1000
alpha-tocopheryl polyethylene glycol succinate

Keywords

  • drug delivery
  • nanoparticles
  • surface coating
  • blood-brain barrier
  • brain tumor
  • VITAMIN-E-TPGS
  • PACLITAXEL TAXOL(R)
  • PLA NANOPARTICLES
  • BIODEGRADABLE NANOPARTICLES
  • P-GLYCOPROTEIN
  • IN-VITRO
  • PARTICLE-SIZE
  • ORAL DELIVERY
  • PLGA NANOPARTICLES
  • CREMOPHOR EL

Cite this

Development of Nanoparticles for Drug Delivery to Brain Tumor : The Effect of Surface Materials on Penetration Into Brain Tissue. / Lei, Chenlu; Davoodi, Pooya; Zhan, Wenbo; Chow, Pierce Kah-Hoe; Wang, Chi-Hwa.

In: Journal of Pharmaceutical Sciences, Vol. 108, No. 5, 05.2019, p. 1736-1745.

Research output: Contribution to journalArticle

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abstract = "Surface-modified poly(d,l-lactic-co-glycolic acid) PLGA nanoparticles (NPs) were fabricated via nanoprecipitation for obtaining therapeutic concentration of paclitaxel (PTX) in brain tumor. The cellular uptake and cytotoxicity of NPs were evaluated on C6 glioma cells in vitro, and BALB/c mice were used to study the brain penetration and biodistribution upon intravenous administration. Results showed that by finely tuning nanoprecipitation parameters, PLGA NPs coated with surfactants with a size around 150 nm could provide a sustained release of PTX for >2 weeks. Surface coatings could increase cellular uptake efficiency when compared with noncoated NPs, and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) showed the most significant enhancement. The in vivo evaluation of TPGS-PLGA NPs showed amplified accumulation (>800{\%} after 96 h) of PTX in the brain tissue when compared with bare NPs and Taxol{\circledR}. Therefore, PLGA-NPs with PLGA-TPGS coating demonstrate a promising approach to efficiently transport PTX across blood-brain barrier in a safer manner, with the advantages of easy formulation, lower production cost, and higher encapsulation efficiency.",
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