Abstract
A microsphere–gel in situ forming implant (MS–Gel ISFI) dual-controlled drug delivery system was applied to a high water-soluble small-molecule compound Rasagiline mesylate (RM) for effective treatment of Parkinson’s disease. This injectable complex depot system combined an in situ phase transition gel with high drug-loading and encapsulation efficiency RM–MS prepared by a modified emulsion-phase separation method and optimized by Box–Behnken design. It was evaluated for in vitro drug release, in vivo pharmacokinetics, and in vivo pharmacodynamics. We found that the RM-MS-Gel ISFI system showed no initial burst release and had a long period of in vitro drug release (60 days). An in vivo pharmacokinetic study indicated a significant reduction (p < .01) in the initial high plasma drug concentration of the RM–MS–Gel ISFI system compared to that of the single RM–MS and RM–in situ gel systems after intramuscular injection to rats. A pharmacodynamic study demonstrated a significant reduction (p < .05) in 6-hydroxydopamine-induced contralateral rotation behavior and an effective improvement (p < .05) in dopamine levels in the striatum of the lesioned side after 28 days in animals treated with the RM–MS–Gel ISFI compared with that of animals treated with saline. MS-embedded in situ phase transition gel is superior for use as a biodegradable and injectable sustained drug delivery system with a low initial burst and long period of drug release for highly hydrophilic small molecule drugs.
Highlights
Parkinson’s disease (PD) is a common progressive neurodegeneration disorder, second only to Alzheimer’s disease (AD)
Based on the results obtained from the plasma concentration–time profiles (Figure 4) and pharmacokinetic parameters (Table S4), it was found that the Rasagiline mesylate (RM)–MS–Gel In situ forming implant (ISFI) system demonstrated a better pharmacokinetic character than the single RM–MS and RM–in situ gel systems did
An RM–MS–Gel ISFI system was prepared by dispersion of RM–MS into an in situ phase transition gel, and applied as a sustained-release depot of RM for the treatment of PD
Summary
Parkinson’s disease (PD) is a common progressive neurodegeneration disorder, second only to Alzheimer’s disease (AD). Preliminary results indicated that the variables mostly affecting the quality of MS prepared by method E were the amount of the drug, the volume ratio of organic (CH2Cl2) to aqueous (water) phase of the primary emulsion, and the stirring speed during solidification. The RM release curve of the RM–MS–Gel ISFI system, consisting of formulations S1-S6 (Figure 3(b,c)), was completely different from that of the RM–MS and RM–in situ gel systems.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
