title: Miktoarm star polymer based multifunctional traceable nanocarriers for efficient delivery of poorly water soluble pharmacological agents.
abstract: A versatile methodology to develop an inherently fluorescent and thus traceable multifunctional nanodelivery platform based on miktoarm polymers is reported. Miktoarm stars containing covalently linked tetraiodofluorescein dye, polyethylene glycol, and polycaprolactone self-assemble into micelles, and integrate multiple functions including fluorescent tags for imaging, a hydrophobic core for drug incorporation, and a hydrophilic corona for micelle stabilization. Curcumin, a pleiotropic but very poorly water-soluble drug, is loaded into these micelles with an efficiency of 25-60 wt%. It leads to a 25 000-fold increase in its aqueous solubility, and a sustained release over a period of 7 d. These micelles are rapidly internalized into murine J774A.1 macrophages, and accumulated into discrete cellular compartments, whereas the free and physically encapsulated dye is diffused in the cytoplasm. Curcumin-loaded micelles reduce lipopolysaccharide-induced nitric oxide release. The studies establish miktoarm star based nanocarriers as highly efficient in tracking their fate and expanding the scope of pharmacological agents with limited utility in experimental medicine.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec, Canada, H3A 0B8; Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec, Canada, H3G 1Y6; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, 71526, Assiut, Egypt.
authors.forename: Ghareb M
authors.initials: GM
authors.lastname: Soliman
authors.forename: Rocio
authors.initials: R
authors.lastname: Redon
authors.forename: Anjali
authors.initials: A
authors.lastname: Sharma
authors.forename: Diana
authors.initials: D
authors.lastname: Mejía
authors.forename: Dusica
authors.initials: D
authors.lastname: Maysinger
authors.forename: Ashok
authors.initials: A
authors.lastname: Kakkar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D005452:Fluoresceins / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005452:Fluoresceins; D008070:Lipopolysaccharides; D008823:Micelles; D053769:Nanocapsules; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Miktoarm polymers; curcumin; inherently fluorescent stars; micelles; nanoparticles; traceable delivery