Impact of rasagiline nanoparticles on brain targeting efficiency via gellan gum based transdermal patch: A nanotheranostic perspective for Parkinsonism

• Published in: International journal of biological macromolecules Vol. 164; pp. 1006 - 1024
• Main Authors: Bali, Nikhil R., Salve, Pramod S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2020
• Subjects: Administration, Cutaneous; Administration, Oral; Animals; Behavior, Animal; Brain - drug effects; Brain - pathology; Brain targeting; Catalepsy; Diffusion; Gellan gum; In-vivo anti-Parkinson study; In-vivo imaging; Indans - pharmacology; Kinetics; Male; Nanoparticles; Parkinsonian Disorders - drug therapy; Particle Size; Polyesters - chemistry; Polysaccharides, Bacterial - chemistry; Rasagiline nanoparticles; Rats; Rats, Wistar; Skin - drug effects; Solvents; Tensile Strength; Theranostic Nanomedicine; Tissue Distribution; Transdermal film; Transdermal Patch; Gellan gum; Brain targeting; In-vivo imaging; Transdermal film; In-vivo anti-Parkinson study; Rasagiline nanoparticles
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.06.261

Rasagiline mesylate is used as first line agent for early management of Parkinson's disease but its water soluble nature creates hurdles to cross blood brain barrier also its low oral bioavailability and rapid elimination requires frequent dosing. Thus present study aims to prepare rasagiline mesylate-nanoparticles (RM-NPs) loaded gellan gum transdermal film for non-invasive; self-administration in elderly patients. PLGA coated RM-NPs prepared by solvent evaporation technique were incorporated into film prepared by solvent casting method. Optimized films with 1.127 g gellan gum and 1.962 % linoleic acid showed enhanced ex-vivo diffusion over a period of 72 h. Comparative pharmacokinetic study revealed increased bioavailability of rasagiline on transdermal application compared to oral route. In-vivo anti-Parkinson activity estimated by behavioural and biochemical analysis indicate reserpine to interfere with monoamine storage hence resulting in development of akinesia and PD-like symptoms in rats. Brain targeting monitored by gamma imaging showed effective brain drug uptake from transdermal film which was also supported by increased brain targeting efficiency estimated from biodistribution study. Thus, the data support efficacy of gellan gum film to target drug to brain region compared to oral route and hence can be employed as a convenient approach for long-term treatment of Parkinson's disease in elderly patients. [Display omitted] •PLGA coating on RM-NPs results in nano sized particles with stable zeta potential and effective brain targeting.•Transdermal film containing RM-NPs prepared from gellan gum showed rate controlled drug release based on concentration of gellan gum in polymer matrix.•Comparative pharmacokinetic profile showed 11-fold and 7-fold increase in AUC with enhanced bioavailability and delayed release for more than 72 h following TDDS application compared to i.v. and oral route.•Reserpine induced akinesia and PD-like symptoms at a lower dose of (0.1 mg/kg/day) subcutaneously, every alternate day over a period of 21 days.•Treatment with transdermal film showed improved catalepsy and open field test with restoration of biochemical content to control value.•In-vivo gamma imaging confirmed drug targeting to brain after transdermal film application with increase drug targeting efficiency and potential.