Molecularly imprinted cyclodextrin nanosponges for the controlled delivery of L-DOPA: perspectives for the treatment of Parkinson's disease

Expert Opin Drug Deliv. 2016 Dec;13(12):1671-1680. doi: 10.1080/17425247.2017.1248398. Epub 2016 Oct 24.

Abstract

Background: L-DOPA is an amino acid precursor to the neurotransmitter dopamine that is extensively used as a prodrug for the treatment of Parkinson's disease. However, L-DOPA is an unstable compound: when exposed to light or added to aqueous solutions, it may degrade, compromising its therapeutic properties.

Methods: In this work, a new type of drug-loaded cyclodextrin-based nanosponge, obtained using molecular imprinting, is described for the prolonged and controlled release of L-DOPA. The molecularly imprinted nanosponges (MIP-NSs) were synthesized by cross-linking β-cyclodextrin with 1,1'-carbonyldiimidazole in DMF in the presence of L-DOPA as a template molecule. TGA, DSC and FTIR analyses were performed to characterize the interactions between L-DOPA and the two nanosponge structures. Quantitative NMR spectroscopy was used to determine the amount and the affinity of L-DOPA entrapped in the nanosponges. The in vitro L-DOPA release kinetics from the NSs were quantitatively determined by HPLC analysis.

Results: The MIP-NSs show a slower and more prolonged release profile than the non-imprinted nanosponges. No degradation of the L-DOPA hosted in the MIP-NSs was observed after long-term storage at room temperature.

Conclusions: The MIP-NSs are a promising alternative for the storage and controlled delivery of L-DOPA.

Keywords: Cyclodextrins; L-DOPA; Nanosponges; in vitro release studies; inclusion compounds; molecularly Imprinted Polymers.

MeSH terms

  • Imidazoles / chemistry
  • Levodopa / administration & dosage*
  • Molecular Imprinting / methods*
  • Parkinson Disease / drug therapy
  • Polymers / chemistry
  • beta-Cyclodextrins / chemistry*

Substances

  • Imidazoles
  • Polymers
  • beta-Cyclodextrins
  • Levodopa
  • N,N-carbonyldiimidazole
  • betadex