title: L-dopa co-drugs in nanostructured lipid carriers: A comparative study.
abstract: This paper describes the production and characterization of nanostructured lipid carriers (NLC) containing four different levodopa (LD) co-drugs (PD), named PDA (3,4-diacetyloxy-LD-caffeic acid co-drug), PDB (lipoic acid-dopamine co-drug), PDC (lipoic acid-3,4-diacetoxy-dopamine co-drug), and PDD (dimeric LD co-drug containing an alkyl linker), with therapeutic potential in Parkinson's disease. These co-drugs were produced with the aim of prolonging the pharmacological activity of LD, enhancing its absorption and protecting it from metabolism. These compounds were characterized by very low water solubility that limits their systemic administration. To improve the solubility of these LDPD, NLC were considered. The obtained NLC showed acceptable particle size and a good stability up to two months from preparation. Cryo-TEM morphological characterization revealed no substantial differences between unloaded and co-drug loaded NLC. In vitro studies showed that the LDPD loaded NLC provided a controlled drug release. Moreover, the enhancement of LDPD stability on the hydrolysis catalysed by foetal calf serum (FCS) esterases or in the presence of lipases was evaluated as compared to a labrasol solution. In presence of esterases PDA-NLC and PDD-NLC showed half-lives higher >3-fold as compared to the corresponding aqueous micellar solution. In the case of PDB-NLC it was found that the stability exceeds the 19h. It can be concluded that NLC represent good strategies to encapsulate lipophilic LD co-drugs, although further studies aimed to deeply evaluate anti-parkinsonian effects in vivo have to be carried on.
authors.affiliation: Department of Life Sciences & Biotechnology, University of Ferrara, Ferrara, Italy. Electronic address: crt@unife.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Cortesi
authors.affiliation: Department of Life Sciences & Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Bayreuth Institute for Macromolecular Research (BIMF) - Soft Matter Electron Microscopy, University of Bayreuth, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Department of Life Sciences & Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pavoni
authors.affiliation: Department of Pharmacy, University of "G. D'Annunzio" Chieti-Pescara, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.affiliation: Department of Life Sciences & Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Sguizzato
authors.affiliation: Department of Pharmacy, University of "G. D'Annunzio" Chieti-Pescara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007980:Levodopa / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010300:Parkinson Disease / Q000188:drug therapy; D008063:Thioctic Acid / Q000737:chemistry
chemical_list: C481009:3,4-diacetyl caffeic acid; D002109:Caffeic Acids; D004337:Drug Carriers; D008055:Lipids; D007980:Levodopa; D008063:Thioctic Acid
keywords: Co-drugs; L-dopa; Nanostructured lipid carriers (NLC); Neurodegenerative disorders