Lithium entrapped chitosan nanoparticles to reduce toxicity and increase cellular uptake of lithium

Environ Toxicol Pharmacol. 2018 Jul:61:79-86. doi: 10.1016/j.etap.2018.05.017. Epub 2018 May 24.

Abstract

Lithium carbonate is an effective drug against bipolar disorders. Direct use of lithium carbonate has been reported to result in lithium toxication and pulmonary complications. With chitosan micro and nanoparticles gaining attention for their protein absorption, drug targeting and improved dissolution rate of sparingly water-soluble drugs, this work has focused on chitosan loaded Li as a possible alternative to Li alone for cellular uptake. Well standardized ionic gelation technique employed in this study resulted in Li loaded chitosan nanoparticles with hydrodynamic diameter below 300 nm and zeta potential of + 30 mV and oval morphology. Through various techniques electrostatic interaction as well as Claritin dependent endocytic pathway is suggested as facilitating 1.3 times increase in cell proliferation in lithium carbonate loaded chitosan nanoparticles treated PC12 cells. A controlled Li release to the extent of less than 50% in 48 h from the nanoparticle was observed. This observation has very high significance as it ensures that the lithium toxicity can be avoided. These results indicated that chitosan is a promising carrier for lithium carbonate and may improve its therapeutic efficacy and also overcome toxicity during its use in the treatment of neuropsychiatric disorders.

Keywords: Bipolar disorder; Bovine serum albumin; Cellular uptake; Chitosan nanoparticles; Lithium carbonate; Nano-carriers.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Proliferation / drug effects
  • Chitosan / administration & dosage*
  • Chitosan / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Lithium Carbonate / administration & dosage*
  • Lithium Carbonate / chemistry
  • Lithium Carbonate / toxicity
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • PC12 Cells
  • Rats

Substances

  • Drug Carriers
  • Lithium Carbonate
  • Chitosan