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 aciddopamine co-drug), PDC (lipoic acid-3,4-diacetoxy-dopamine co-drug), and PDD(dimeric LDco-drug containing an alkyl linker),with therapeutic potential in Parkinson's disease. These co-drugswere producedwith the aimof prolonging the pharmacological activity of LD, enhancing its absorption and protecting it frommetabolism. These compoundswere characterized by very lowwater 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 N3-fold as compared to the corresponding aqueous micellar solution. In the case of PDB-NLC it was found that the stability exceeds the 19 h. 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.

L-dopa co-drugs in nanostructured lipid carriers: a comparative study

CORTESI, Rita
Primo
;
ESPOSITO, Elisabetta
Secondo
;
PAVONI, Gabriella;SGUIZZATO, Maddalena;
2017

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 aciddopamine co-drug), PDC (lipoic acid-3,4-diacetoxy-dopamine co-drug), and PDD(dimeric LDco-drug containing an alkyl linker),with therapeutic potential in Parkinson's disease. These co-drugswere producedwith the aimof prolonging the pharmacological activity of LD, enhancing its absorption and protecting it frommetabolism. These compoundswere characterized by very lowwater 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 N3-fold as compared to the corresponding aqueous micellar solution. In the case of PDB-NLC it was found that the stability exceeds the 19 h. 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.
Cortesi, Rita; Esposito, Elisabetta; Drechsler, M.; Pavoni, Gabriella; Cacciatore, I.; Sguizzato, Maddalena; Di Stefano, A.
File in questo prodotto:
File Dimensione Formato  
Ldopa codrugs.2017.pdf

solo gestori archivio

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.53 MB
Formato Adobe PDF
1.53 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
11392_2367326_postprint_Cortesi_Rita.pdf

accesso aperto

Descrizione: post print
Tipologia: Post-print
Licenza: Creative commons
Dimensione 1.88 MB
Formato Adobe PDF
1.88 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2367326
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact