Ivan Hevus

Programmed Photodegradation of Polymeric/Oligomeric Materials Derived from Renewable Bioresources†

Renewable polymeric materials derived from biomass with built-in phototriggers were synthesized and evaluated for degradation under irradiation of UV light. Complete decomposition of the polymeric materials was observed with recovery of the monomer that was used to resynthesize the polymers.

Invertible micellar polymer assemblies for delivery of poorly water-soluble drugs.

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.

Interfacial micellar phase transfer using amphiphilic invertible polymers

Micelles formed from new amphiphilic invertible polymers (AIPs) can sequester hydrophobic molecules in water and transfer their payload to a non-polar phase. The amount of material transferred depends primarily on micellar loading capacity. Increasing the lipophilicity of the AIP composition increases the amount of material transferred. The obtained data indicate that AIPs have the potential to serve as an alternative for administration of polymer-based nanopharmaceuticals. Invertible polymeric micelles can potentially facilitate controlled release of poorly water-soluble agents incorporated within the micellar interior when compared to release by thermodynamically stable conventional (non-invertible) micelles.

Anticancer efficiency of curcumin-loaded invertible polymer micellar nanoassemblies

Abstract Recently synthesized amphiphilic invertible polymers (AIPs) are considered as good candidates for micellar delivery of hydrophobic (poorly water-soluble) drugs. Macromolecules of the AIPs self-assemble into invertible micellar assemblies (IMAs) by increasing polymer concentration in solution, and are capable of inverting macromolecular conformation by changing solvent polarity. Being nontoxic against human cells, IMAs are able to solubilize, deliver, and release poorly water-soluble curcumin to treat osteosarcoma cells. The loading into micellar polymer nanoassemblies significantly improves the bioavailability of curcumin in aqueous medium. The mechanism of curcumin release from IMAs depends on AIP chemical structure and might result from macromolecular inversion only, due to changing polarity of the environment. Loaded with curcumin IMAs are stable in aqueous (polar) medium. However, once the drug-loaded assemblies approach cell membrane (less polar), it triggers the macromolecular inversion and drug release due to the enhanced interactions between the membrane and the drug.

Amphiphilic Invertible Polymers and Their Applications

Amphiphilic invertible polymers (AIPs) are novel smart macromolecules. Synthesized from short lipophilic and hydrophilic constituents that are alternately or randomly distributed along the polymer backbone, the AIP macromolecules possess an enhanced flexibility and rapidly respond to changes in an environmental polarity by changing their macromolecular conformation. By increasing a solution concentration, the AIP macromolecules self-organize into micellar assemblies that can change their physicochemical properties in response to changes in a medium polarity. The micellar assemblies from AIPs can be applied for the development of smart nanoreactors for the synthesis of metal and semiconductor nanoparticles of a controlled shape and size, as well as for the growth of fibrillar carbon nanostructures and the formation of smart nanocontainers for drug delivery. Synthetic routes to (1) amphiphilic invertible polyurethanes based on poly(ethylene glycol), polytetrahydrofuran, and 2,4-tolylene diisocyanate and (2) amphiphilic invertible polyesters based on poly(ethylene glycol) and aliphatic dicarboxylic acids were elaborated, and the corresponding polymers were successfully synthesized. The effect of reaction conditions on the reaction course and the macromolecular configuration of the resulting polymers were revealed. It was demonstrated that the chemical nature and structure of the macromolecules of the amphiphilic invertible polyurethanes and polyesters determine the self-assembly of the AIP macromolecules, both in an aqueous and organic media, resulting in a formation of micellar assemblies, which can serve as nanoreactors, nanocontainers, and nanocarriers.