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

J Control Release. 2005 Feb 16;102(3):689-97. doi: 10.1016/j.jconrel.2004.11.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Carbidopa / administration & dosage*
  • Carbidopa / pharmacokinetics
  • Drug Evaluation, Preclinical / methods
  • Levodopa / administration & dosage*
  • Levodopa / pharmacokinetics
  • Male
  • Microspheres*
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Rats

Substances

  • Levodopa
  • Carbidopa