Vitamin-Derived Nanolipoidal Carriers for Brain Delivery of Dimethyl Fumarate: A Novel Approach with Preclinical Evidence.
Various oral treatment options have been reported for relapsing multiple sclerosis. Recently, dimethyl fumarate (DMF) has been approved for the management of the same. Though effective, DMF is associated with concerns like multiple dosing, patient incompliance, gastrointestinal flushing, lower brain permeation, and economic hurdles. Henceforth, the objective of the present study was to develop vitamin-based solid lipid nanoparticles (SLNs) for effective brain delivery of DMF with a promise of once-a-day dosing. The developed SLNs were characterized for micromeritics, morphology, entrapment efficiency, drug loading and in vitro drug release. Caco-2 and SH-SY5Y cell lines were used to assess the intestinal permeability and neuronal uptake. Pharmacokinetic and biodistribution studies were performed on rats. The developed nanometeric lipidparticles were able to control the drug release and substantially enhance the Caco-2 as well as SH-5YSY cell permeability. The developed systems not only enhanced the oral bioavailability of the drug, but also offered substantially elevated brain drug levels to that of plain drug. The drug was protected from liver and biological residence was increased, indicating promising potential of the carriers in effective brain delivery of DMF. Enhanced bioavailability and elevated bioresidence of DMF by vitamin-based SLNs provided the evidence for once-a-day delivery potential for DMF in the management of neurological disorders.
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan , Bandar Sindri, Distt. Ajmer, Rajasthan, India -305817.
Pramod
P
Kumar
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh, India -160014.
Gajanand
G
Sharma
UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University , Chandigarh, India -160014.
Rajendra
R
Kumar
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan , Bandar Sindri, Distt. Ajmer, Rajasthan, India -305817.
Ruchi
R
Malik
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh, India -160014.|UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University , Chandigarh, India -160014.
Bhupinder
B
Singh
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh, India -160014.
O P
OP
Katare
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan , Bandar Sindri, Distt. Ajmer, Rajasthan, India -305817.
Kaisar
0000-0001-8159-8005
K
Raza
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects; D018938:Caco-2 Cells; D002762:Cholecalciferol; D000069462:Dimethyl Fumarate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004224:Diterpenes; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008055:Lipids; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D000084562:Retinyl Esters; D014018:Tissue Distribution; D014801:Vitamin A / Q000031:analogs & derivatives
D004224:Diterpenes; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008055:Lipids; D000084562:Retinyl Esters; D014801:Vitamin A; D002762:Cholecalciferol; C009166:retinol acetate; D000069462:Dimethyl Fumarate
SH-SY5Y cells; SLNs; Vitamin D3; drug delivery; multiple sclerosis; once-a-day delivery; vitamin A acetate