title: PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model.
abstract: Stroke is a one of the leading causes of disease and deaths worldwide, which causes irreversible deterioration of the central nervous system. Curcuminoids are reported to have a potential role in the amelioration of cerebral ischemia but they exhibit low serum and tissue levels due to low solubility and poor absorption. Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)-loaded PNIPAM nanoparticles (NPs) were prepared by free radical polymerization and characterized for particles size, entrapment efficiency, zeta potential, in vitro release and ex vivo permeation study. Optimized CUR, DMC and BDMC-loaded NPs had the mean size of 92.46 ± 2.8, 91.23 ± 4.2 and 94.28 ± 1.91 nm; zeta potential of -16.2 ± 1.42, -15.6 ± 1.33 and -16.6 ± 1.21 mV; loading capacity of 39.31 ± 3.7, 38.91 ± 3.6 and 40.61 ± 3.6% and entrapment efficiency of 84.63 ± 4.2, 84.71 ± 3.99 and 85.73 ± 4.31%, respectively. Ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectroscopy based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency and brain drug-targeting potential studies post-intranasal (i.n.) administration which showed enhanced bioavailability of curcuminoids in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) and reduced cytokines levels (TNF-α and IL-1β) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of curcuminoids NPs. Finally, the toxicity study was performed which revealed safe nature of developed NPs.
authors.affiliation: a Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy.|b UPLC-MS Lab, Department of Pharmaceutics, Faculty of Pharmacy.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: a Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy.
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: c Department of Medical Elemental and Toxicology, Faculty of Science , and.
authors.forename: Sadiq
authors.initials: S
authors.lastname: Umar
authors.affiliation: a Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: d Department of Chemistry, Faculty of Science , Hamdard University , New Delhi , India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Samim
authors.affiliation: a Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy.|b UPLC-MS Lab, Department of Pharmaceutics, Faculty of Pharmacy.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D036381:Diarylheptanoids; D016503:Drug Delivery Systems / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D020521:Stroke / Q000188:drug therapy; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D000180:Acrylic Resins; D036381:Diarylheptanoids; C052970:poly-N-isopropylacrylamide; C034786:bisdemethoxycurcumin; D003474:Curcumin; C050229:demethoxycurcumin
keywords: Bisdemethoxycurcumin; brain drug-targeting potential; brain-targeting efficiency; curcumin; demethoxycurcumin; intranasal