Preparation and evaluation of rotigotine-loaded implant for the treatment of Parkinson's disease and its evolution study.
OBJECTIVE
To develop rotigotine-loaded implants (RI) to achieve continuous release of rotigotine for long duration for the treatment of Parkinson's disease (PD).


METHODS
RI was prepared by hot-melt extrusion method using poly (lactide-co-glycolide) (PLGA) as the matrix. In vitro drug release was optimized by drug loading, melting temperature during preparing process and additives. The surface and internal morphology of RI was imaged by SEM. The in vivo release profile of RI was investigated on rat.


RESULTS
RI prepared with PLGA 7525 5A showed sustained release of 40 days while suffering a lag phase, which was significantly shortened by blending 5050 2A and mannitol in the matrix. RI prepared by 7525 5A/5050 2A/mannitol = 55:10:5 (rotigotine 30%) showed a 40-day sustained release in vivo with no lag phase. The drug release from RI was also affected by drug loading and melting temperature probably due to the drug state existed in the implant. The evolution of implants during release process was correlated well with the drug release kinetics.


CONCLUSIONS
RI could achieve sustained drug release for 40 days which could supply an alternative of continuous dopaminergic stimulation (CDS) for the treatment of PD.
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China.
Aiping
A
Wang
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China.
Yanxiang
Y
Liu
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China; State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, No. 9 Baoyuan Road, Yantai, Shandong 264003, PR China.
Rongcai
R
Liang
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China; State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, No. 9 Baoyuan Road, Yantai, Shandong 264003, PR China.
Xuemei
X
Zhang
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China.
Kaoxiang
K
Sun
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China.
Zimei
Z
Wu
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, PR China.
Wanhui
W
Liu
Continuous dopaminergic stimulation; Parkinson’s disease; Rotigotine-loaded implant; Sustained release