Synthesis and characterization of thermally responsive pluronic F127-chitosan nanocapsules for controlled release and intracellular delivery of small molecules

Wujie Zhang, Kyle Gilstrap, Laying Wu, K. C. Remant Bahadur, Melissa A. Moss, Qian Wang, Xiongbin Lu, Xiaoming He

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

In this study, we synthesized empty core-shell structured nanocapsules of Pluronic F127 and chitosan and characterized the thermal responsiveness of the nanocapsules in size and wall-permeability. Moreover, we determined the feasibility of using the nanocapsules to encapsulate small molecules for temperature-controlled release and intracellular delivery. The nanocapsules are ∼37 nm at 37 °C and expand to ∼240 nm when cooled to 4 °C in aqueous solutions, exhibiting >200 times change in volume. Moreover, the permeability of the nanocapsule wall is high at 4 °C (when the nanocapsules are swollen), allowing free diffusion of small molecules (ethidium bromide, MW = 394.3 Da) across the wall, while at 37 °C (when the nanocapsules are swollen), the wall-permeability is so low that the small molecules can be effectively withheld in the nanocapsule for hours. As a result of their thermal responsiveness in size and wall-permeability, the nanocapsules are capable of encapsulating the small molecules for temperature-controlled release and intracellular delivery into the cytosol of both cancerous (MCF-7) and noncancerous (C3H10T1/2) mammalian cells. The cancerous cells were found to take up the nanocapsules much faster than the noncancerous cells during 45 min incubation at 37 °C. Moreover, toxicity of the nanocapsules as a delivery vehicle was found to be negligible. The Pluronic F127-chitosan nanocapsules should be very useful for encapsulating small therapeutic agents to treat diseases particularly when it is combined with cryotherapy where the process of cooling and heating between 37 °C and hypothermic temperatures is naturally done.

Original languageEnglish
Pages (from-to)6747-6759
Number of pages13
JournalACS Nano
Volume4
Issue number11
DOIs
StatePublished - 23 Nov 2010

Keywords

  • Chitosan
  • Controlled release
  • Intracellular delivery
  • Nanocapsule
  • Pluronic F127
  • Thermal responsiveness
  • Wall-permeability

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