title: Invertible micellar polymer assemblies for delivery of poorly water-soluble drugs.
abstract: Strategically designed amphiphilic invertible polymers (AIPs) are capable of (i) self-assembling into invertible micellar assemblies (IMAs) in response to changes in polarity of environment, polymer concentration, and structure, (ii) accommodating (solubilizing) substances that are otherwise insoluble in water, and (iii) inverting their molecular conformation in response to changes in the polarity of the local environment. The unique ability of AIPs to invert the molecular conformation depending on the polarity of the environment can be a decisive factor in establishing the novel stimuli-responsive mechanism of solubilized drug release that is induced just in response to a change in the polarity of the environment. The IMA capability to solubilize lipophilic drugs and deliver and release the cargo molecules by conformational inversion of polymer macromolecules in response to a change of the polarity of the environment was demonstrated by loading IMA with a phytochemical drug, curcumin. It was demonstrated that four sets of micellar vehicles based on different AIPs were capable of delivering the curcumin from water to an organic medium (1-octanol) by means of unique mechanism: AIP conformational inversion in response to changing polarity from polar to nonpolar. The IMAs are shown to be nontoxic against human cells up to a concentration of 10 mg/L. On the other hand, the curcumin-loaded IMAs are cytotoxic to breast carcinoma cells at this concentration, which confirms the potential of IMA-based vehicles in controlled delivery of poorly water-soluble drug candidates and release by means of this novel stimuli-responsive mechanism.
authors: Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, North Dakota 58108, United States.
authors: Ivan
authors: I
authors: Hevus
authors: Amit
authors: A
authors: Modgil
authors: Justin
authors: J
authors: Daniels
authors: Ananiy
authors: A
authors: Kohut
authors: Chengwen
authors: C
authors: Sun
authors: Shane
authors: S
authors: Stafslien
authors: Andriy
authors: A
authors: Voronov
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D002072:Butylene Glycols / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D002072:Butylene Glycols; D008823:Micelles; D053769:Nanocapsules; D011108:Polymers; D013501:Surface-Active Agents; C524501:poly(tetrahydrofuran); D014867:Water; D011092:Polyethylene Glycols; D003474:Curcumin; D020003:1-Octanol