Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies

• Published in: PloS one 2018-03, Vol.13 (3), p.e0193451
• Main Authors: Ahmad, Aftab, Abuzinadah, Mohammed F, Alkreathy, Huda M, Banaganapalli, Babajan, Mujeeb, Mohd
• Format: Article
• Language: English
• Subjects: Acids; Analgesics; Analgesics - chemistry; Analgesics - metabolism; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Arthritis; Arthritis, Experimental - drug therapy; Biological activity; Biology and Life Sciences; Carriers; Cyclooxygenase 1 - chemistry; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - chemistry; Cyclooxygenase 2 - metabolism; Cyclooxygenase-1; Cyclooxygenase-2; Cytokines; Diclofenac; Drug Carriers - chemistry; Drug delivery; Drug Liberation; Entrapment; Enzymes; Evaluation; Evaporation; Female; Freund's adjuvant; In vivo methods and tests; Inflammation; Interleukin 1; Interleukin-1 - antagonists & inhibitors; Laboratories; Leaves; Lipids; Lipids - chemistry; Male; Medicine and Health Sciences; Mice; Molecular docking; Molecular Docking Simulation; Nanoparticles; Ocimum sanctum; Ocimum sanctum - chemistry; Particle Size; Penetration; Permeability; Pharmacology; Physical Sciences; Physicochemical properties; Plant extracts; Plant Extracts - chemistry; Plant Extracts - metabolism; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Pollutants; Polydispersity; Population; Protein Conformation; Proteins; Rats; Rats, Wistar; Research and Analysis Methods; Rheumatism; Rheumatoid arthritis; Skin; Skin - drug effects; Skin - metabolism; Surfactants; Triterpenes - chemistry; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ursolic Acid; Zeta potential
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193451

Ursolic acid (UA) is a promising molecule with anti-inflammatory, analgesic and potential anti-arthritic activity. This study was undertaken to make formulation and evaluation of Ocimum sanctum L. leaf extract (OLE) loaded nano-structured lipid carriers (OLE-NLCs) for improved transdermal delivery of UA. Different surfactants, solid lipids and liquid lipids were used for the preparation of NLCs. The NLCs were developed using emulsion solvent diffusion and evaporation method. Different physicochemical properties, entrapment efficacy, in vitro release evaluation, and ex vivo permeation studies of the prepared NLCs were carried out. The in vivo anti-arthritic activity of OLE-loaded NLC gel and control gel formulation (OLE free NLC gel) against Complete Freund's Adjuvant (CFA) induced arthritis in wister albino rats was also carried out. OLE-NLCs were composed of spherical particles having a mean particle size of ~120 nm, polydispersity index of ~0.162 and zeta potential of ~ -27 mV. The high entrapment efficiency (EE) of UA ~89.56% was attained. The in vitro release study demonstrated a prolonged release of UA from the NLCs up to 12 h. The developed formulation was found to be significantly better with respect to the drug permeation amount with an enhancement ratio of 2.69 as compared with marketed formulation. The in vivo biological activity investigations, studies showed that the newly prepared NLCs formulation of OLE showed excellent anti-arthritic activity and the results were found at par with standard marketed diclofenac gel for its analgesic and anti-arthritic activities. These results were also supported by radiological analysis and molecular docking studies. The overall results proved that the prepared OLE-NLCs were very effective for the treatment of arthritis and the results were found at par with standard marketed the standard formulation of diclofenac gel.