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.
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Authors | Anjali Singh, Iqbal Ahmad, Sayeed Ahmad, Zeenat Iqbal, Farhan J Ahmad |
Journal | Drug development and industrial pharmacy
(Drug Dev Ind Pharm)
Vol. 42
Issue 9
Pg. 1524-36
(Sep 2016)
ISSN: 1520-5762 [Electronic] England |
PMID | 26902951
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers
- Delayed-Action Preparations
- Drug Carriers
- Lipids
- Protective Agents
- Stilbenes
- Suspensions
- Resveratrol
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Topics |
- Administration, Oral
- Animals
- Biological Availability
- Biomarkers
(blood)
- Chemistry, Pharmaceutical
(methods)
- Delayed-Action Preparations
(administration & dosage, chemistry, pharmacokinetics)
- Drug Carriers
(chemistry)
- Drug Delivery Systems
(methods)
- Drug Stability
- Lipids
(chemistry)
- Liver
(drug effects)
- Liver Cirrhosis
(blood, drug therapy)
- Male
- Nanoparticles
(administration & dosage, chemistry)
- Particle Size
- Protective Agents
(administration & dosage, chemistry)
- Rats
- Rats, Wistar
- Resveratrol
- Stilbenes
(administration & dosage, chemistry, pharmacokinetics)
- Suspensions
(administration & dosage, chemistry)
- X-Ray Diffraction
(methods)
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