title: Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.
abstract: The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 μm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, PR China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Wei
authors.forename: Ying-Rui
authors.initials: YR
authors.lastname: Han
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Quan
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liao
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D004339:Drug Compounding; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry; D000074241:Peanut Oil; D010938:Plant Oils / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine; D013535:Suspensions; D014018:Tissue Distribution
chemical_list: D000074241:Peanut Oil; D010938:Plant Oils; D011355:Prodrugs; D013535:Suspensions; D012110:Reserpine; D003474:Curcumin