Enhanced retention of celecoxib-loaded solid lipid nanoparticles after intra-articular administration.
OBJECTIVE
The objective of this study was to determine whether the retention of celecoxib in inflamed articular joints of arthritic rats could be enhanced by incorporation of the drug into solid lipid nanoparticles.


METHODS
Celecoxib-loaded solid lipid nanoparticles (SLN) were prepared by emulsification and high-pressure homogenisation, then characterised by particle size analysis and scanning electron microscopy. In vitro drug-release studies indicated that the nanoparticles exhibited sustained release of celecoxib and the release pattern followed quasi-Fickian diffusion. The biocompatibility of solid lipid nanoparticles was evaluated by histopathology of the rat joints after intra-articular injection in normal rats. Celecoxib and celecoxib-loaded SLN were labelled with (99m)Tc and the labelling parameters were optimised to obtain maximum labelling efficiency. The labelled complexes were administered intra-articularly and the pharmacokinetics and biodistribution were determined.


RESULTS
The nanoparticles showed no inflammatory infiltrates 3 and 7 days post-intra-articular injection, proving their biocompatibility and suitability for intra-articular use. Free celecoxib underwent rapid clearance from the inflamed articular joints into the systemic circulation, while the celecoxib-loaded SLN were associated with significantly lower blood levels compared with free celecoxib. Free celecoxib was found to have been extensively distributed to organs of the reticuloendothelial system such as the liver, lungs and spleen. In contrast, celecoxib-loaded nanoparticles demonstrated significantly lower distribution to the reticuloendothelial organs. The articular concentrations of celecoxib-loaded nanoparticles in the inflamed joints were 16-fold higher at 4 hours post-injection and 15-fold higher at 24 hours post-injection than free celecoxib concentrations, indicating greater and prolonged retention in the inflamed articular joints.


CONCLUSIONS
Celecoxib-loaded SLN with its greater intra-articular retention and sustained-release properties would be a beneficial delivery system for the effective treatment of arthritis and is expected to result in prolonged anti-arthritic activity of celecoxib.
Thakkar
Hetal
H
Drug Delivery Research Laboratory, Pharmacy Department, Center of Relevance and Excellence in NDDS, MS University, Fatehgunj, Gujarat, India.
Kumar Sharma
Rakesh
R
Murthy
R S R
RS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005227:Fatty Acids; D007270:Injections, Intra-Articular; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D016861:Cyclooxygenase Inhibitors; D005227:Fatty Acids; D011720:Pyrazoles; D013449:Sulfonamides; C086409:glyceryl behenate; D000068579:Celecoxib