Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease

Piribedil (PBD) is an anti-Parkinson’s drug that gained interest recently due to its unique pharmacological profile. But its clinical use is severely limited by drug delivery issues like high dosing frequency (up to 5 tablets/day), low oral bioavailability (<10%), severe GI side-effects, etc. In this work, we have developed solid lipid nanoparticles (PBD-SLNs) to access the nose to brain pathways for direct uptake of PBD. PBD-SLNs were optimized using design of experiments approach to a mean particle size of 358 nm, and drug loading of 15%.

Highlights

Piribedil is an anti-Parkinson’s drug with unique pharmacological advantages.

Its clinical use is limited due to high dosing frequency of the oral tablets.

SLNs were developed for intranasal delivery of PBD to improve direct brain uptake.

In situ gel loaded SLNs were found to be superior over plain piribedil suspension.

Direct nose to brain transport with in situ gel loaded SLNs of Piribedil was 27%.

The optimized PBD-SLNs were found to be nearly spherical in shape and showed good stability. Further, the SLNs were loaded in thermoresponsive Methyl Cellulose in situ gel (PBD-SLN-ISG) to delay mucociliary clearance upon intranasal administration in rats. Intranasal administration at the olfactory region was achieved with a cannula-microtip setup. In vivo pharmacokinetic studies showed that PBD-SLN-ISG increased the PBD (AUC)_brain by about 4-folds and reduced the (C_max)_plasma by 2.3-folds when compared to plain intranasal suspension of PBD (PBD-Susp).

Further, PBD-Susp showed limited direct nose to brain uptake with direct transport percentage (DTP) values less than 0, while the optimized PBD-SLN-ISG showed DTP value of 27% indicating efficient direct nose to brain uptake.

Read the article here

Article information: Chandra Teja Uppuluri, Punna Rao Ravi, Avantika V. Dalvi. Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease, International Journal of Pharmaceutics, Volume 606, 2021. https://doi.org/10.1016/j.ijpharm.2021.120881.