Roflumilast-loaded nanostructured lipid carriers attenuate oxidative stress and neuroinflammation in Parkinson's disease model

• Published in: Journal of drug targeting 2024-10, p.1-16
• Main Authors: Roy, Dhritiman, Balasubramanian, Shivaramakrishnan, Kunte, Prajwal P, Natarajan, Jawahar, Sola, Piyong, Rymbai, Emdormi, M R, Praharsh Kumar
• Format: Article
• Language: English
• ISSN: 1061-186X; 1029-2330; 1029-2330
• DOI: 10.1080/1061186X.2024.2408724

Parkinson's disease (PD) is a progressive neurodegenerative disorder with limited symptomatic treatment options. Targeting phosphodiesterase 4 (PDE4) has shown a promising result in several preclinical studies. In our study we aim to repurpose US FDA-approved PDE4 inhibitor for PD. Through study, we identified roflumilast (ROF) as the potential candidate targeting PDE4B2. In Drosophila PD expressing the A30P mutant α-synuclein model, ROF exhibited anti-PD effects as indicated by negative geotaxis and antioxidant activities. Given the low brain distribution of ROF (< 50%) at clinical doses, incorporation into nanostructured lipid carriers (NLCs) was carried out to enhanced blood-brain barrier permeability. In vitro release studies indicated sustained ROF release from NLCs (≈75%) over 24 hours. Single-dose oral toxicity studies reported no mortality or toxicity signs. ROF-loaded NLCs significantly alleviated behavioural deficits, increased antioxidant parameters (P