title: Nanocarrier based formulation of Thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies.
abstract: This research aims to formulate and characterize solid lipid nanoparticles (SLNs) of Thymoquinone (THQ-SLNs) for the effective treatment of liver cirrhosis. Formulations were prepared using solvent injection method and optimized by the Box-Behnken experimental design to get the desired particle size having maximized entrapment efficiency as well as percentage release. Optimized THQ-SLNs (ST-1) with appropriate characteristics (particle size=166.1±10.96 nm; zeta potential=-11.34±3.54 mV; entrapment efficiency=71.60±3.85%; maximum % release=70.95±2.47%) were fabricated. DSC and XRD studies were carried out which collectively proved the reduced crystallinity and stability enhancing effect of the SLNs. Improved drug stability was further established by the subjection of the THQ-SLNs to accelerated stability studies (as per ICH guidelines) in contrast to the THQ-suspension. In vivo studies revealed a nearly 5 fold increase in the bioavailability of ST-1 (AUC(0→∞)=2998.91±260.503 μg/mL/h) as compared to THQ suspension (AUC(0→∞)=484.23±21.755 μg/mL/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (SGOT, SGPT and ALP) after oral administration of THQ-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol (PCM)-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections.
authors.affiliation: Nanoformulation Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Singh
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.forename: Sohail
authors.initials: S
authors.lastname: Akhter
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D008055:Lipids / Q000737:chemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D014961:X-Ray Diffraction
chemical_list: D016227:Benzoquinones; D008055:Lipids; C003466:thymoquinone