N. Aditya and K.M. Praveen

BITS-Pilani, Hyderabad Campus

Purpose

Rasagiline mesylate (RM) is chemically designated as N-Propargyl-1(R)-aminoindan mesylate. RM is currently approved as initial monotherapy or adjunct therapy to levodopa for treatment of signs and symptoms of idiopathic Parkinson’s disease in the United States and Europe. It has poor oral bioavailability of approximately 36%. It undergoes extensive hepatic first pass metabolism. RM is primarily biotransformed by N-dealkylation and hydroxylation. The present study aimed at developing oral polymeric nanoparticles of RM using Poly-ε-caprolactone (PCL) to improve its oral bioavailability.

Methods

Drug loaded PCL nanoparticles were produced by multiple emulsion (w/o/w)method. Particle size and zeta potential were measured by Malvern Zetasizer. In-vitro drug release profiling was done in pH 1.2, 6.8 and 7.4 buffers.Characterization of the polymeric nanoparticles was done using FT-IR and DSC studies. Comparative bioavailability studies of liquid oral solution of RM and polymeric RM nanoparticles were carried out on male Wistar rats (n=3).

Results

The average particle size was 250 ± 5 nm for RM-PCL nanoparticles with negative charge on the surface  of the particles. Encapsulation efficiency was found to be 41 ± 5 %. Both FT-IR and DSC data showed no interaction between RM and PCL  in nanoparticles. In-vitro drug release profile showed less than 10 ± 2 % release in pH 1.2 buffer (upto 2 h), less than 14.5 ± 2 % release in pH 6.8 buffer (upto 12 h) and over 85 ± 2 % release in pH 7.4 buffer (in 48 h). It was demonstrated that RM loaded PCL nanoparticles could significantly (p<0.01) enhance oral bioavailability of RM. The enhancement was found to be over 3.3 folds for RM-PCL nanoparticles compared to pure drug solution.

Conclusion

Manufacturing method employed resulted in polymeric nanoparticles of desired size (less than 300 nm) with sufficient  drug encapsulation. The in-vivo studies on rats showed promising improvement in the bioavaialibility of the drug. Further clinical investigations need to be conducted to prove the utility of these nanocarrier systems in humans.