title: Preparation of novel curcumin-loaded multifunctional nanodroplets for combining ultrasonic development and targeted chemotherapy.
abstract: Recently, a new class of multifunctional nanodroplets that combine the properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. We studied the formation mechanism of nanodroplets of a drug and its application in chemotherapy. Curcumin was loaded in polymeric micelles as a anti-cancer drug using polyethylene glycol block-poly(caprolactone) with encapsulation efficiency of 95.60%. At room temperature, the developed systems comprised perfluorocarbon nanodroplets stabilized by walls comprising biodegradable block copolymers. Upon heating to 37°C, the nanodroplets were converted to nano/microbubbles. Under ultrasound, nanobubbles cavitated and collapsed, resulting in release of the encapsulated drug. The percentage release of curcumin-loaded nanodroplets by insonation was 90.95%, showing enhancement compared with the non-ultrasound group. Nanodroplets strongly retained the loaded drugs in vivo yet, under ultrasound-mediated vaporization, they released the drugs, thereby implementing effective targeting into the tumor. The tumor inhibition of the group in which curcumin-loaded nanodroplets were combined with ultrasound was 71.30%, more than that of the group of curcumin-loaded nanodroplets (53.00%). Nanodroplets showed high enhancement of anti-cancer effects under ultrasound. Upon intravenous injection, a long-lasting, strong and selective ultrasound contrast was observed, suggesting their coalescence into larger, highly echogenic microbubbles. These multifunctional nanodroplets, which manifest excellent therapeutic and ultrasound properties, could be promising anti-cancer drug delivery systems.
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou, 510515, PR China.
authors.forename: Gangjian
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan, 750004, PR China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave., Guangzhou, 510515, PR China. Electronic address: jhchen06@126.com.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D008099:Liver / Q000000981:diagnostic imaging; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013010:Sonication; D047368:Tumor Burden / Q000187:drug effects; D014463:Ultrasonography
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C016240:polycaprolactone; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Curcumin; Drug delivery; Nanodroplets; PEG-PCL; Ultrasound