title: A novel monolithic controlled delivery system of resveratrol for enhanced hepatoprotection: nanoformulation development, pharmacokinetics and pharmacodynamics.
abstract: The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window particle size of 150-200 nm having maximum entrapment efficiency as well as % release. Optimized resveratrol solid lipid nanoparticles (RV-SLNs) (SR-1) of appropriate characteristics (particle size = 191.1 ± 10.44 nm; zeta potential= -13.56 ± 4.14 mV; entrapment efficiency = 75.23 ± 3.85%; maximum % release = 80.53 ± 3.99%) were produced. Differential scanning calorimetry and X-ray diffraction studies were carried out which collectively proved the reduced crystallinity and stability enhancing the effect of the SLNs. Improved drug stability was further established by the appreciable shelf-life of the formulation from International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-recommended accelerated stability studies. In vivo studies revealed nearly five-fold increase in the bioavailability of SR-1 (AUC0→∞=3411 ± 170.34 µg/ml/h) as compared to RV suspension (AUC0→∞=653.5 ± 30.10 µg/ml/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (serum glutamic oxalo-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase) after oral administration of RV-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections. Finally, reverse transcriptase-polymerase chain reaction studies were conducted on isolated liver mRNA from SR-1 treated animals and significant down-regulation of tissue inhibitor of metalloproteinases-1 and nuclear factor-kB was witnessed.
authors.affiliation: a Nanoformulation Research Lab , Jamia Hamdard , New Delhi , India ;|b Department of Pharmaceutical Medicine, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India ;
authors.forename: Anjali
authors.initials: A
authors.lastname: Singh
authors.affiliation: a Nanoformulation Research Lab , Jamia Hamdard , New Delhi , India ;
authors.forename: Iqbal
authors.initials: I
authors.lastname: Ahmad
authors.affiliation: c Bioactive Natural Product Lab , Jamia Hamdard , New Delhi , India.
authors.forename: Sayeed
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: a Nanoformulation Research Lab , Jamia Hamdard , New Delhi , India ;
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: a Nanoformulation Research Lab , Jamia Hamdard , New Delhi , India ;
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D015415:Biomarkers; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D020011:Protective Agents; D013267:Stilbenes; D013535:Suspensions; D000077185:Resveratrol
keywords: Controlled release; monolithic dosage form; passive targeting; resveratrol solid lipid nanoparticles; solvent injection method