title: pH-sensitive nanoparticles of curcumin-celecoxib combination: evaluating drug synergy in ulcerative colitis model.
abstract: Inflammatory bowel diseases, which largely comprise ulcerative colitis (UC) and Crohn's disease, are increasingly posing as a global threat because of the incompetence of the current therapy in the entire patient population. This necessitates the identification of alternative therapeutic molecules or their combinations, which may serve as effective first-line or maintenance therapeutics. In this quest, celecoxib, a selective cyclooxygenase-2 inhibiting nonsteroidal anti-inflammatory agent and curcumin, a natural antioxidant and anti-inflammatory agent, have both been found to be useful in alleviating UC. Furthermore, studies involving their combination have proved synergistic action of these two agents. In the current investigation, we have formulated pH-sensitive nanoparticles of curcumin-celecoxib combination as a potential therapy for UC. Synergistic action of the drug combination, delivery advantages of nanosized carriers, and pH-sensitive nature of the polymer were collectively hypothesized to reduce the overall toxicity and total dose of celecoxib and provide enhanced efficacy for mitigating UC. The hypothesis was confirmed in a UC model in rats, where pH-sensitive nanoparticles of the drug combination were found to be more efficacious than nanoparticles of either drugs or drug/s suspension. Further, the blank nanoparticles did not exhibit any therapeutic effect, thereby confirming efficacy of the drug combination for treating UC.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400019, India.
authors.forename: Dalapathi
authors.initials: D
authors.lastname: Gugulothu
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Vandana
authors.initials: V
authors.lastname: Patravale
authors.forename: Prajakta
authors.initials: P
authors.lastname: Dandekar
mesh_terms: D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D001682:Biological Availability; D000068579:Celecoxib; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000201:enzymology; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004338:Drug Combinations; D004339:Drug Compounding; D004357:Drug Synergism; D004563:Electrochemistry; D005079:Excipients; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D005079:Excipients; D011720:Pyrazoles; D013449:Sulfonamides; D009195:Peroxidase; D013482:Superoxide Dismutase; D003474:Curcumin; D000068579:Celecoxib
keywords: colonic drug delivery; drug delivery systems; drug targeting; nanoparticles; natural products; oral drug delivery; polymeric drug carrier; site-specific delivery; targeted drug delivery