Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 49; no. 1; pp. 511 - 522
• Main Authors: Shah, Pranav, Dubey, Priya, Vyas, Bhavin, Kaul, Ankur, Mishra, Anil Kumar, Chopra, Dimple, Patel, Priya
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Administration, Intranasal; Animals; Anticonvulsants - administration & dosage; Anticonvulsants - chemistry; Anticonvulsants - pharmacokinetics; Anticonvulsants - pharmacology; Bioavailability; Biodistribution; Brain; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Dosage; Drug Carriers - chemistry; Drug Liberation; Emulsification; Entrapment; Epilepsy; Epilepsy - drug therapy; Evaporation; gamma scintigraphy; Intranasal administration; Lactic Acid - chemistry; Lamotrigine; Lamotrigine - administration & dosage; Lamotrigine - chemistry; Lamotrigine - pharmacokinetics; Lamotrigine - pharmacology; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - chemistry; nose-to-brain delivery; Particle size; Pharmacodynamics; Pharmacokinetics; PLGA nanoparticles; Polydispersity; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polylactide-co-glycolide; Rabbits; Radionuclide Imaging; Rats; Scintigraphy; Seizures; Side effects; Thermodynamic properties; Tissue Distribution; Zeta potential; epilepsy; biodistribution; gamma scintigraphy; PLGA nanoparticles; nose-to-brain delivery; Lamotrigine
• ISSN: 2169-1401; 2169-141X; 2169-141X
• DOI: 10.1080/21691401.2021.1939709

The present study aimed to investigate the brain targeting efficacy of Lamotrigine (LTG) loaded PLGA nanoparticles (LTG-PNPs) upon intranasal administration. LTG-PNPs were fabricated through the emulsification-solvent evaporation technique and evaluated for % Entrapment efficiency, particle size, in-vitro release, surface morphology, crystallinity, ex-vivo permeation & thermal behaviour. Biodistribution, gamma scintigraphy, and pharmacodynamic studies were performed in BALB/c mice, New Zealand rabbits, and Wistar rats respectively. LTG-PNPs exhibited % EE 71%; particle size 170.0 nm; Polydispersity index 0.191; zeta potential −16.60 mV. LTG-PNPs exhibited a biphasic release pattern. Biodistribution and gamma scintigraphy studies proved a greater amount of LTG in the brain following intranasal delivery of LTG-PNPs in comparison to LTG-SOL. Pharmacodynamic studies demonstrated delayed seizure onset time with LTG-PNPs in comparison to LTG-SOL. Intranasal administration of LTG-PNPs provided prolonged release, higher bioavailability, and better brain targeting bypassing the BBB. The developed formulation could be administered as a once-a-day formulation that would reduce the dosing frequency; dose; dose-related side effects; cost of the therapy and would be beneficial in the management of epilepsy as compared to the LTG-SOL. However, the proof of concept generated through these studies needs to be further validated in higher animals and human volunteers.