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.

Glyco-Nanoparticles Made from Self-Assembly of Maltoheptaose-block-Poly(methyl methacrylate): Micelle, Reverse Micelle, and Encapsulation

“…However, much less studies have been related to solvent-responsive copolymers which switch their conformation in response to solvent polarity from micelle-type assemble (hydrophilic shell) in aqueous media to reverse micelle-type assemble (hydrophobic shell) in organic media. 28,29 Indeed, copolymers with such ability could find uses in applications such as drug carrier, since they favor the hydrophobic drug transfer from the micelles core in aqueous environment (e.g., bloodstream) to the nonpolar interface (e.g., lipid bilayers). 28,30 Thus, we describe, in this study, the synthesis of "hybrid" diblock copolymers consisting of maltoheptaose as the saccharide block and poly(methyl methacrylate) (PMMA) as the synthetic block.…”

Invertible Micellar Polymer Nanoassemblies Target Bone Tumor Cells But Not Normal Osteoblast Cells

“…The chemical structure of the PEG 600 PTHF 650 was confirmed by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy and Fourier transform infrared spectroscopy [28]. To confirm the formation of micelles from PEG 600 PTHF 650 in aqueous solution, CMC was measured via solubilization of a fluorescent probe, pyrene, to study the association behavior of amphiphilic polymers [28]. …”

“…The latter unique ability can be a decisive factor in AIP-mediated controlled delivery using a new and different inversion mechanism of lipophilic drugs release to various cancerous cells. In our most recent work, curcumin-loaded IMAs displayed anticancer efficiency by delivering water-insoluble drugs to breast carcinoma cells [28]. In addition, the loading into micellar polymer nanoassemblies significantly improved the bioavailability of curcumin in aqueous medium.…”

“…In addition, the loading into micellar polymer nanoassemblies significantly improved the bioavailability of curcumin in aqueous medium. As a result, it was shown that, being nontoxic against human cells, IMAs are able to solubilize, deliver and release poorly water-soluble curcumin molecules to treat tumor cells [28]. Depending on the chemical structure of the AIP, the release of curcumin from IMAs might result exclusively from macromolecular inversion due to changes in local environmental polarity.…”

“…The release profile can be controlled by AIP structure and concentration. The curcumin-loaded micellar polymer nanoassemblies were stable in a homogenous polar aqueous medium, but once they approach the less polar cell biomembrane surface, stimuli-triggered conformational inversion occurred [28]. The latter enhances interaction between the drug and the biomembrane, and thus, drug release from the nanoassemblies.…”