title: Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.
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.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Ankara, Turkey.
authors.forename: Betül
authors.initials: B
authors.lastname: Arica
authors.forename: H Süheyla
authors.initials: HS
authors.lastname: Kaş
authors.forename: Amir
authors.initials: A
authors.lastname: Moghdam
authors.forename: Nejat
authors.initials: N
authors.lastname: Akalan
authors.forename: A Atilla
authors.initials: AA
authors.lastname: Hincal
mesh_terms: D000818:Animals; D001711:Biotransformation; D002230:Carbidopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007980:Levodopa / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats
chemical_list: D007980:Levodopa; D002230:Carbidopa