EVALUATION AND NEUROPROTECTIVE ANALYSIS OF FAST AND SLOW-RELEASE PELLETS FOR TRIPLE COMBINATION THERAPY IN PARKINSON’S DISEASE

Abstract

Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder with the loss of dopaminergic neurons in the substantia nigra, which results in motor and non-motor dysfunction. Although the classic approach to management with Levodopa continues, its usefulness is blighted by a short half-life, pulsatile receptor stimulation and motor oscillations. The use of a combination therapy of Carbidopa and Entacapone increases bioavailability but still does not provide for stable dopaminergic tone. In this study, we investigated the neuroprotective effects of a new multiparticulate capsule comprising fast-, slow- and immediate -release pellets of Levodopa, Carbidopa and Entacapone in an MPTP lesioned rat model of PD. Multiparticulate capsules were prepared by mixing fast-releasing pellets coated with HPMC/EC, slow-releasing pellets coated with Eudragit L100 and S100 and timed releasing pellets layered with HPMC E15. Wistar rats were grouped into five categories as, normal control, standard group, toxic group, low pellet treatment dose and high pellet treatment dose. Behavioural parameters (elevated plus maze, locomotor activity), biochemical estimations (GPx, CAT, SOD, LPO) and histopathological examination were done during the first 21 days. Pellet based therapy produced dose-dependent improvements. The high dose of D adjusted retention transfer latency to near control values, prevented the fall in locomotor scores and enzyme activities and hyper-peroxidation. Reduced inflammatory accumulation and preserved neuronal integrity in comparison with toxic control were histopathologically confirmed. The results show that pellet triple therapy provides long-term dopaminergic stimulation and neuroprotection, representing a non-invasive alternative to infusion or implant systems. This formulation has the potential to enhance compliance, decrease motor fluctuations and contribute to a more patient-centered approach of PD.