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.

Asymmetric AB3 Miktoarm Star Polymers: Synthesis, Self‐Assembly, and Study of Micelle Stability Using AF4 for Efficient Drug Delivery

“…Blank and curcumin‐loaded miktoarm micelles were prepared by the co‐solvent evaporation method . AB 3 miktoarms (10 mg) with different PCL lengths were dissolved in 0.5 mL tetrahydrofuran (THF) with or without curcumin at a mixing ration of 1:0.5 miktoarm/curcumin by weight ratio.…”

“…Blank and curcumin-loaded miktoarm micelles were prepared by the co-solvent evaporation method. [23] AB 3 miktoarms (10 mg) with different PCL lengths were dissolved in 0.5 mL tetrahydrofuran (THF) with or without curcumin at a mixing ration of 1:0.5 miktoarm/ curcumin by weight ratio. The solution was added dropwise to magnetically stirred deionized water for a final concentration in miktoarm of 5 mg Á mL À1 for PCL 3 200/4 700/6 800 or 10 mg Á mL À1 for PCL 18 000 (Table S2).…”

Miktoarm Star Polymers: Branched Architectures in Drug Delivery

“…Owing to their tailorable architecture, superior CMCs, improved drug loading, and sustained drug release, there has been much recent interest in miktoarm star polymer-based assemblies for drug delivery [ 21 , 25 , 26 ]. Drug incorporation into micelles has been shown to have varied effects on the size of miktoarm micelles, where it can lower, increase, or have a negligible effect upon drug encapsulation [ 24 , 42 , 47 , 48 , 49 ]. Though generally, a decrease in size has been attributed to good polymer-drug compatibility [ 47 , 49 , 57 ].…”

“…Drug incorporation into micelles has been shown to have varied effects on the size of miktoarm micelles, where it can lower, increase, or have a negligible effect upon drug encapsulation [ 24 , 42 , 47 , 48 , 49 ]. Though generally, a decrease in size has been attributed to good polymer-drug compatibility [ 47 , 49 , 57 ]. One of the beneficial effects of including multiple branching arms as in miktoarm stars, is in increasing drug loading content into their self-assemblies.…”

Sequential Reactions for Post-polymerization Modifications

“…In their first step, azide-capped PEG was clicked onto one triple bond of (3,5-diethynylphenyl)methanol (Scheme 29) [65]. The other triple bond was used to attach a polyethylene containing an azide moiety and one bromide chain end.…”