title: Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.
abstract: We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality.
authors.affiliation: Department of Chemical Engineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szymusiak
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D007773:Lactates / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D007773:Lactates; D011091:Polyesters; D011108:Polymers; D013535:Suspensions; C088513:poly(lactic acid-ethylene glycol); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D009020:Morphine; D003474:Curcumin