Olive Oil-Based Reverse Microemulsion for Stability and Topical Delivery of Methotrexate: In Vitro

Hydrolysis of pharmaceutically active molecules can be in control under a confined environment of water-in-oil microemulsion. Stability of model drug methotrexate (MTX) in a sodium bis­(2-ethylhexyl) sulfosuccinate (AOT) and olive oil microemulsion system has been evaluated. The physicochemical properties of AOT-MTX-water-olive oil reverse microemulsion (MTX-RM) were examined by UV–vis, Fourier transform infrared, and X-ray diffraction techniques, and the hydrodynamic size was determined by dynamic light scattering techniques and morphologies were characterized by a transmission electron microscope and atomic force microscope. In vitro permeation of MTX-RM through treated skin and its mechanism are evaluated by a UV–visible spectrophotometer, confocal laser scanning microscope, differential scanning calorimeter, and attenuated total reflecting infrared spectroscopy (ATR). The interaction of MTX with the AOT headgroup in confined environment RM enhanced the stability of MTX without affecting the molecular integrity at room temperature. Chemical stability of MTX in MTX-RM (W0 = 5) is significantly higher (∼97%) at room temperature for the study period of 1 year than in MTX-RM (W0 = 15) (∼72%). Interaction of MTX with the AOT headgroup is also visualized by a high-resolution transmission electron microscope and is in correlation with FT-IR data of MTX-RM. The skin fluxes of MTX are 15.1, 19.75, and 22.75 times higher at water content (W0) of 5, 10, and 15, respectively, in MTX-RM in comparison to aqueous solution of MTX. The enhanced amounts of the MTX were detected using CLSM in hair follicles, sweat glands, and epidermis layer of the skin. Merging of T2, T3, and T4 thermal peaks in one broad peak in treated skin endothermograph shows that carrier MTX-RM affects the lipid as well protein structure of the treated skin. ATR data of treated skin showed an increase in the intensity of the carbonyl peak at 1750 cm–1 (lipid), shifting of the amide II peaks, and separation of peaks in the range of 1060 to 1000 cm–1 (vibration mode of −CH2OH, C–O stretching, and C–OH bending peak of the carbohydrate) in comparison to control skin, which indicates that MTX-RM interacts with glycolipid and glycoprotein through carbohydrate hydroxy groups

Effect of Biphenyl Spacers on the Anionic Polymerization of 2‑(4′-Vinylbiphenyl-4-yl)pyridine

The pyridine-containing monomer 2-(4′-vinylbiphenyl-4-yl)­pyridine (VBPPy), synthesized by the Suzuki coupling reaction, was successfully polymerized using diphenylmethylpotassium (DPM-K) as an initiator within 360 min at −78 °C, resulting in 100% yield and polydispersity <1.3, as with the living anionic polymerization of 2-vinylpyridine (2VP) and 2-(4-vinylphenyl)­pyridine (VPPy). By the block copolymerization of VBPPy with 2VP, VPPy, and methyl methacrylate (MMA), it was proven that the nucleophilicity of living poly­(2-(4′-vinylbiphenyl-4-yl)­pyridine) is between that of living poly­(2-(4-vinylphenyl)­pyridine) and that of living poly­(methyl methacrylate). Among the block copolymers, PVBPPy-b-PMMA was used to make nanocomposites in which gold (Au) nanoparticles (NPs) were present only in the PVBPPy zone of the phase-separated PVBPPy-b-PMMA) (fVBPPy = 0.23) film

Formation of Intermicellar-Chained and Cylindrical Micellar Networks From an Amphiphilic Rod−Coil Block Copolymer: Poly(<i>n</i>-hexyl isocyanate)-<i>block</i>-poly(2-vinylpyridine)

Morphologies of the poly(n-hexyl isocyanate)-block-poly(2-vinylpyridine) (PHIC-b-P2VP, fP2VP = 0.3) amphiphilic rod−coil block copolymer were studied in rod-selective chloroform (CHCl3), both-block-soluble tetrahydrofuran (THF), and CHCl3/THF mixed solvent systems. Spherical, solid micelles with a P2VP core and PHIC shell were formed in CHCl3, whereas a microphase-separated liquid crystalline morphology was prominent in the presence of THF. In the CHCl3/THF mixed solvent system, a unique long-range intermicellar-chained network (v/v = 7/3) and a more evolved cylindrical micellar network (v/v = 3/7) were remarkably formed, respectively. PHIC-b-P2VP network nanostructures were used as a template for the in situ synthesis of Au nanoparticles (8 nm) selectively within the functional P2VP core domains

Effect of Solvent Composition on Transformation of Micelles to Vesicles of Rod−Coil Poly(<i>n</i>-hexyl isocyanate-<i>block</i>-2-vinylpyridine) Diblock Copolymers

The self-aggregation behavior of an amphiphilic rod−coil block copolymer of poly(n-hexyl isocyanate-block-2-vinylpyridine) (PHIC189-b-P2VP228) (fP2VP = 0.78, Mn = 24.5K) in a tetrahydrofuran (THF)/water system was examined using dynamic light scattering (DLS), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM). The presence of a certain amount of water in the THF-based polymer solution induced a morphological transition from spherical solid micelles to open mouth platelike vesicles. The size of the aggregates increased with an increase in water content in the mixed solvent of THF/water. In the range of 30−40% water, the polymer formed vesicles with an interdigitated architecture of poly(n-hexyl isocyanate) (PHIC) at the center of the membrane and with the poly(2-vinylpyridine) (P2VP) block forming the outer layers and pointing toward the solvent. However, at higher water contents, the thickness of the bilayer increased due to the rearrangement of the vesicle membrane from a flip-flop to a lamellar architecture. After the degradation of the PHIC from the vesicles at basic pH, hollow spherical aggregates remained stable. After removing the THF from the mixed solvent using dialysis, large-sized compound vesicles were formed

2‑Isopropenyl-2-oxazoline: Well-Defined Homopolymers and Block Copolymers via Living Anionic Polymerization

Poly­(2-isopropenyl-2-oxazoline) (PIPOx) has drawn significant attention for numerous applications. However, the successful living anionic polymerization of 2-isopropenyl-2-oxazoline has not been reported previously. Herein, we describe how well-defined PIPOx with quantitative yields, controlled molecular weights from 6800 to over 100 000 g/mol and low polydispersity indices (PDI ≤ 1.17) were synthesized successfully via living anionic polymerization using diphenyl­methyl­potassium/diethyl­zinc (DPM-K/Et₂Zn) in tetrahydrofuran (THF) at 0 °C. In particular, we report the precise synthesis of well-defined PIPOx with the highest molecular weight ever reported (over 100 000 g/mol) and low PDI of 1.17. The resulting polymers were characterized by ¹H and ¹³C nuclear magnetic resonance spectroscopy (NMR) along with size exclusion chromatography (SEC). Additionally, the reactivity of living PIPOx was investigated by crossover block copolymerization with styrene (St), 2-vinylpyridine (2VP), and methyl methacrylate (MMA). It was found that the nucleophilicity of living PIPOx is of this order: living PS > living P2VP > living PMMA > living PIPOx. The self-assembly behavior in bulk of PIPOx-<i>b</i>-PS-<i>b</i>-PIPOx triblock copolymers having different block ratios of 10:80:10 and 25:50:25 was studied using transmission electron microscopy (TEM). The formation of spherical and lamellar nanostructures, respectively, was observed

Well-Defined Ambipolar Block Copolymers Containing Monophosphorescent Dye

Well-defined ambipolar block copolymers containing carbazole, oxadiazole moieties, and only one homoleptic iridium­(III) complex between the carbazole and oxadiazole blocks were successfully synthesized by sequential living anionic polymerization with controlled molecular weights (Mw), a narrow molecular weight distribution (Mw/Mn < 1.15), and a high conversion yield (98–100%). The optimum conditions for the successful controlled synthesis of an oxadiazole-containing the homopolymer of poly­(2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole) have been established by controlling the nucleophilicity strength of the carbanion. In addition, the location and concentration of the homoleptic iridium­(III) complex were controlled by linking it to 1,1-diphenylethylene, which exhibits monoaddition characteristics in the main chain of the block copolymer

Exploration of the Mechanism for Self-Emulsion Polymerization of Amphiphilic Vinylpyridine

A rare self-assembly behavior is observed in a hydrophilic monomer (4-vinylpyridine) (4VP) when polymerized in water with a hydrophilic initiator that results in the production of monodisperse polymeric nanoparticles in a single step. This behavior mimics the behavior obtained with the more commonly reported amphiphilic block copolymers. The synthesis and self-assembly of homopolymer nanoparticle from 4VP without the use of any cross-linker, stabilizing agent, surfactant, or polymeric emulsifier are described along with fundamental aspects of the mechanism of this polymerization. This facile and robust procedure enabled the production of highly monodisperse P4VP nanoparticle with a tunable size ranging from 80 to 445 nm. For the first time, we have investigated the growth mechanism of these polymeric nanoparticles to clarify the mechanism of polymeric nanoparticle formation. This work also provides direct visible evidence through transmission electron microscopy (TEM) images at the nanometer scale, which helps in obtaining a better understanding of the mechanism of self-assembly. The effect of temperature on the size of the polymeric nanoparticles was also examined along with the effect of initiator, monomer, and solvent concentrations. We therefore report a versatile and scalable process for the production of monodisperse polymeric nanoparticles, which we call self-emulsion polymerization (SEP)