ABSTRACT
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature. RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and FosB/ΔFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/ΔFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and ΔFosB in striatum.
Subject(s)
Chitosan/pharmacology , Dopamine Agents/pharmacology , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Dyskinesia, Drug-Induced/metabolism , Dyskinesia, Drug-Induced/prevention & control , Levodopa/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Animals , Biocompatible Materials/pharmacology , Blotting, Western , Corpus Striatum/drug effects , Dopamine and cAMP-Regulated Phosphoprotein 32/analysis , Dopamine and cAMP-Regulated Phosphoprotein 32/drug effects , Dyskinesia, Drug-Induced/etiology , Extracellular Signal-Regulated MAP Kinases/analysis , Extracellular Signal-Regulated MAP Kinases/drug effects , Immunohistochemistry , Liposomes , MAP Kinase Signaling System , Male , Nanoparticles , Parkinson Disease/drug therapy , Phosphorylation/drug effects , Proto-Oncogene Proteins c-fos/analysis , Proto-Oncogene Proteins c-fos/drug effects , Random Allocation , Rats, Sprague-Dawley , Reproducibility of Results , Treatment OutcomeABSTRACT
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum