Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats

Arica B., Kas H., Moghdam A., Akalan N., Hincal A.

JOURNAL OF CONTROLLED RELEASE, vol.102, no.3, pp.689-697, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 102 Issue: 3
  • Publication Date: 2005
  • Doi Number: 10.1016/j.jconrel.2004.11.004
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.689-697
  • Hacettepe University Affiliated: Yes


The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation. (C) 2004 Elsevier B.V. All rights reserved.