title: Induction of an in vitro reversible hypometabolism through chitosan-based nanoparticles.
abstract: OBJECTIVE
  Chitosan-based nanoparticles (NPs) were prepared to promote intracellular sustained delivery of the synthetic delta opioid D-Ala(2)-D-Leu(5)-enkephalin (DADLE), prolonging peptide activity and inducing a safe and reversible hypometabolic state.
  
  
  METHODS
  NPs were prepared by combining ionotropic gelation and ultrasonication treatment. NP uptake studies and the effects of encapsulated DADLE on HeLa cells proliferation were tested by transmission electron microscopy (TEM) analysis, by immuno-fluorescence and immuno-cytochemistry.
  
  
  RESULTS
  DADLE-loaded NPs are produced with suitable characteristics, a satisfactory process yield (55.4% ± 2.4%) and encapsulation efficiency (64.6% ± 2.1%). NPs are effective in inducing a hypometabolic stasis at a 10(-4) M DADLE concentration. Moreover, as seen from the immunofluorescence study, the effect persists through the recovery period (72 h). Indeed, NPs labelled by anti-enkephalin antibody inside cell nucleus reassert that the in vivo release of the peptide can be prolonged with respect to the case of free peptide supply.
  
  
  CONCLUSIONS
  The nanoparticulate drug delivery system described seems to be effective in inducing and prolonging a sort of hibernation-like state in the cells.
authors.affiliation: Department of Drug Sciences, University of Pavia, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colonna
authors.forename: R
authors.initials: R
authors.lastname: Dorati
authors.forename: B
authors.initials: B
authors.lastname: Conti
authors.forename: T
authors.initials: T
authors.lastname: Modena
authors.forename: M
authors.initials: M
authors.lastname: Biggiogera
authors.forename: A
authors.initials: A
authors.lastname: Spedito
authors.forename: I
authors.initials: I
authors.lastname: Genta
mesh_terms: D048271:Chitosan; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D016308:Enkephalin, Leucine-2-Alanine / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016308:Enkephalin, Leucine-2-Alanine; D048271:Chitosan