The Influence of PVP Polymer Topology on the Liquid Crystalline Order of Itraconazole in Binary Systems.

This study presents a novel approach by utilizing poly(vinylpyrrolidone)s (PVPs) with various topologies as potential matrices for the liquid crystalline (LC) active pharmaceutical ingredient itraconazole (ITZ). We examined amorphous solid dispersions (ASDs) composed of ITZ and (i) self-synthesized linear PVP, (ii) self-synthesized star-shaped PVP, and (iii) commercial linear PVP K30. Differential scanning calorimetry, X-ray diffraction, and broad-band dielectric spectroscopy were employed to get a comprehensive insight into the thermal and structural properties, as well as global and local molecular dynamics of ITZ-PVP systems. The primary objective was to assess the influence of PVPs' topology and the composition of ASD on the LC ordering, changes in the temperature of transitions between mesophases, the rate of their restoration, and finally the solubility of ITZ in the prepared ASDs. Our research clearly showed that regardless of the PVP type, both LC transitions, from smectic (Sm) to nematic (N) and from N to isotropic (I) phases, are effectively suppressed. Moreover, a significant difference in the miscibility of different PVPs with the investigated API was found. This phenomenon also affected the solubility of API, which was the greatest, up to 100 µg/mL in the case of starPVP 85:15 w/w mixture in comparison to neat crystalline API (5 µg/mL). Obtained data emphasize the crucial role of the polymer's topology in designing new pharmaceutical formulations.

Synthesis of thermo-responsive polymer gels composed of star-shaped block copolymers by copper-catalyzed living radical polymerization and click reaction.

In recent times, there has been a significant surge in research interest surrounding thermo-responsive water-soluble polyacrylamides, primarily due to their intriguing capability to undergo significant solubility changes in water. These polymers exhibit the remarkable ability to shift from a soluble to an insoluble state in response to temperature variations. The capacity of these polymers to dynamically respond to temperature changes opens up exciting avenues for designing smart materials with tunable properties, amplifying their utility across a spectrum of scientific and technological applications. Researchers have been particularly captivated by the potential applications of thermo-responsive water-soluble polyacrylamides in diverse fields such as drug delivery, gene carriers, tissue engineering, sensors, catalysis, and chromatography separation. This study reports the construction and functionalization of polymer gels consisting of a polymer network of polyacrylamide derivatives with nano-sized structural units. Specifically, thermo-responsive polymer gels were synthesized by combining well-defined star-shaped polymers composed of polyacrylamide derivatives with a multifunctional initiator and linking method through a self-accelerating click reaction. The polymerization system employed a highly living approach, resulting in polymer chains characterized by narrow molecular weight distributions. The method's high functionality facilitated the synthesis of a temperature-responsive block copolymer gel composed of N-isopropyl acrylamide (NIPA) and N-ethyl acrylamide (NEAA). The resulting polymer gel, comprising star-shaped block copolymers of NIPA and NEAA, showcases smooth volume changes with temperature jumps.

This approach's versatility was showcased by creating networks using widely-used vinyl polymers. It can generate various functional and nearly ideal gels and elastomers, allowing for investigating fundamental aspects of polymer networks.

The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole.

In this paper, we propose one-step synthetic strategies for obtaining well-defined linear and star-shaped polyvinylpyrrolidone (linPVP and starPVP). The produced macromolecules and a commercial PVP K30 with linear topology were investigated as potential matrices for suppressing metronidazole (MTZ) crystallization. Interestingly, during the formation of binary mixtures (BMs) containing different polymers and MTZ, we found that linear PVPs exhibit maximum miscibility with the drug at a 50:50 weight ratio (w/w), while the star-shaped polymer mixes with MTZ even at a 30:70 w/w. To explain these observations, comprehensive studies of MTZ-PVP formulations with various contents of both components were performed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained results clearly showed that the polymer's topology plays a significant role in the type of interactions occurring between the matrix and MTZ. Additionally, we established that for MTZ-PVP 50:50 and 75:25 w/w BMs, linear polymers have the most substantial impact on inhibiting the crystallization of API. The star-shaped macromolecule turned out to be the least effective in stabilizing amorphous MTZ at these polymer concentrations. Nevertheless, long-term structural investigations of the MTZ-starPVP 30:70 w/w system (which is not achievable for linear PVPs) demonstrated its complete amorphousness for over one month.

Acyclic diene metathesis polymerization and heck polymer-polymer conjugation for the synthesis of star-shaped block copolymers.

Three- and four-arm star shaped polymers, as well as diblock copolymers, are synthesized via acyclic diene metathesis (ADMET) polymerization. This is accomplished by using an asymmetric α,ω-diene containing a terminal double bond and an acrylate, which is polymerized in the presence of multifunctional acrylates as selective and irreversible chain transfer agents using Hoveyda-Grubbs second generation catalyst. High cross-metathesis selectivities are achieved at low temperatures enabling good control over molecular weights. Furthermore, additional polyethyleneglycol (PEG) blocks are attached to these polymers via Heck coupling of the acrylate end-groups of these polymers with aryl iodide functionalized PEG, obtaining three- and four-arm star shaped di- and triblock copolymers with molecular weights up to 31 kDa.

An Amphiphilic Star-Shaped Polymer (Star-PEG-PCL2) used as a Stationary Phase for GC.

A star-shaped polymer (Star-PEG-PCL2) was synthesized with PCL and PEG and used as a stationary phase for gas chromatography. The statically coated Star-PEG-PCL2 column exhibited an efficiency of 2260 plates/m determined by naphthalene at 120 °C and moderate polarity. The Star-PEG-PCL2 column showed high resolution performance for isomers of a wide ranging polarity, including methylnaphthalenes, halogenated benzenes, nitrobenzene, phenols, and anilines, and displayed dual-nature selectivity for a mixture of 17 analytes. Also, the Star-PEG-PCL2 column exhibited good separation performance and column inertness for Grob test mixture and a series of cis-/trans-isomers. In addition, it exhibited advantageous separation performance over the commercial HP-35 and PEG-20M columns for chloroaniline and bromoaniline isomers through its unique three-dimensional framework. In conclusion, it has good potential as a new stationary phase for separating a variety of analytes because of its special structure and excellent separation performance.

Hydrophobic Drug Carrier from Polycaprolactone-b-Poly(Ethylene Glycol) Star-Shaped Polymers Hydrogel Blend as Potential for Wound Healing Application.

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and 1H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. Mn for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01-1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer-Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology.

Star-Shaped Polydimethylsiloxanes with Organocyclotetrasilsesquioxane Branching-Out Centers: Synthesis and Properties.

New non-crystallizable low-dispersity star-shaped polydimethylsiloxanes (PDMS) containing stereoregular cis-tetra(organo)(dimethylsiloxy)cyclotetrasiloxanes containing methyl-, tolyl- and phenyl-substituents at silicon atoms and the mixture of four stereoisomers of tetra[phenyl(dimethylsiloxy)]cyclotetrasiloxane as the cores were synthesized. Their thermal and viscous properties were studied. All synthesized compounds were characterized by a complex of physicochemical analysis methods: nuclear magnetic resonance (NMR), FT-IR spectroscopy, gel permeation chromatography (GPC), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), viscometry in solution, rheometry, and Langmuir trough study.

Synthesis and Hydrogelation of Star-Shaped Graft Copolypetides with Asymmetric Topology.

To study the self-assembly and hydrogel formation of the star-shaped graft copolypeptides with asymmetric topology, star-shaped poly(L-lysine) with various arm numbers were synthesized by using asymmetric polyglycerol dendrimers (PGDs) as the initiators and 1,1,3,3-tetramethylguanidine (TMG) as an activator for OH groups, followed by deprotection and grafting with indole or phenyl group on the side chain. The packing of the grafting moiety via non-covalent interactions not only facilitated the polypeptide segments to adopt more ordered conformations but also triggered the spontaneous hydrogelation. The hydrogelation ability was found to be correlated with polypeptide composition and topology. The star-shaped polypeptides with asymmetric topology exhibited poorer hydrogelation ability than those with symmetric topology due to the less efficient packing of the grafted moiety. The star-shaped polypeptides grafted with indole group on the side chain exhibited better hydrogelation ability than those grafted with phenyl group with the same arm number. This report demonstrated that the grafted moiety and polypeptide topology possessed the potential ability to modulate the polypeptide hydrogelation and hydrogel characteristics.

Influence of Salt on the Self-Organization in Solutions of Star-Shaped Poly-2-alkyl-2-oxazoline and Poly-2-alkyl-2-oxazine on Heating.

The water-salt solutions of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines were studied by light scattering and turbidimetry. The core was hexaaza[26]orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. NaCl and N-methylpyridinium p-toluenesulfonate were used as salts. Their concentration varied from 0-0.154 M. On heating, a phase transition was observed in all studied solutions. It was found that the effect of salt on the thermosensitivity of the investigated stars depends on the structure of the salt and polymer and on the salt content in the solution. The phase separation temperature decreased with an increase in the hydrophobicity of the polymers, which is caused by both a growth of the side radical size and an elongation of the monomer unit. For NaCl solutions, the phase separation temperature monotonically decreased with growth of salt concentration. In solutions with methylpyridinium p-toluenesulfonate, the dependence of the phase separation temperature on the salt concentration was non-monotonic with minimum at salt concentration corresponding to one salt molecule per one arm of a polymer star. Poly-2-alkyl-2-oxazine and poly-2-alkyl-2-oxazoline stars with a hexaaza[26]orthoparacyclophane core are more sensitive to the presence of salt in solution than the similar stars with a calix[n]arene branching center.

Temperature and H2O2-operated nano-valves on mesoporous silica nanoparticles for controlled drug release and kinetics.

Temperature and H2O2 dual-responsive nanoparticles were fabricated from ferrocene modified mesoporous silica (MSN-Fc) and ß-cyclodextrin-poly(N-isopropylacrylamide) (ß-CD-PNIPAM) star-shaped polymer due to the host-guest interactions for controlled drug release. The formation and structure of ß-CD-PNIPAM@MSN-Fc composite nanoparticles was confirmed by FTIR, TGA, TEM and N2 adsorption-desorption isotherms. The size of nanoparticles was about 100-150 nm with well-ordered mesoporous structure and PNIPAM chains coating on the surface as outer shell. The channels of MSNs and hydrophobic cavities of ß-CD were all contributed to the high drug loading capacity for nanoparticles. The release of DOX from nanoparticles was enhanced with the increase of temperature above LCST or adding H2O2 in ambient O2. The release kinetics were studied using different models to explain drug release mechanism. Furthermore, the drug loaded composite nanoparticles exhibited excellent anti-cancer activity.

Star-Shaped Poly(2-ethyl-2-oxazoline) and Poly(2-isopropyl-2-oxazoline) with Central Thiacalix[4]Arene Fragments: Reduction and Stabilization of Silver Nanoparticles.

The interaction of silver nitrate with star-shaped poly(2-ethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) containing central thiacalix[4]arene cores, which proceeds under visible light in aqueous solutions at ambient temperature, was studied. It was found that this process led to the formation of stable colloidal solutions of silver nanoparticles. The kinetics of the formation of the nanoparticles was investigated by the observation of a time-dependent increase in the intensity of the plasmon resonance peak that is related to the nanoparticles and appears in the range of 400 to 700 nm. According to the data of electron and X-ray spectroscopy, scanning and transmission electron microscopy, X-ray diffraction analysis, and dynamic light scattering, the radius of the obtained silver nanoparticles is equal to 30 nm. In addition, the flow birefringence experiments showed that solutions of nanoparticles have high optical shear coefficients.

A star-shaped POSS-containing polymer for cleaner leather processing.

A water-based silsesquioxane (POSS)-containing polymer, POSS-PAA, was synthesized by using octavinyl-POSS (V-POSS) and acrylic acid (AA) via interfacial polymerization. The TEM of POSS-PAA showed that the polymer formed a core-shell structure in aqueous solution and was well-dispersed. The star-shaped POSS-PAA and linear PAA were both tanned with 3.5% chromium tanning agent, and leather hide was tanned with 3.5% chromium tanning agent as a control. The results showed that the shrinkage temperature of wet-blue leather treated by POSS-PAA was increased by 3.5 °C than that of the control. The thickening rate of the POSS-PAA treated wet-blue leather samples was increased by 21% and 96% than the linear PAA-treated leather and the control leather, respectively. The EDS results suggested that the POSS-PAA pre-treated leather had a higher chromium content than the others, and the chromium distribution from the leather flesh side to the grain side was uniform. Moreover, the Cr2O3 content in both the POSS-PAA and the PAA pre-treated tanning waste water was reduced by about 50%, compared to the control waste. The COD and BOD of the POSS-PAA pre-tanning waste were decreased compared to the others. Therefore, POSS-PAA appeared to be promising for promoting the development of cleaner leather production.

Stereocomplexation, Thermal and Mechanical Properties of Conetworks Composed of Star-Shaped l-Lactide, d-Lactide and ε-Caprolactone Oligomers Utilizing Sugar Alcohols as Core Molecules.

It is important to develop tailor-made biodegradable/biocompatible polymer networks usable for biomaterials whose thermal and mechanical properties are easily controlled by changing the composition. We synthesized sugar-alcohol-based polymer networks (SPN-mscLAO/3CLO, m = 4, 5 or 6) by the crosslinking reactions of erythritol, xylitol or sorbitol-based m-armed star-shaped l-lactide and d-lactide oligomers (HmSLLAO and HmSDLAO), a glycerol-based 3-armed star-shaped ε-caprolactone oligomer (H3SCLO) and hexamethylene diisocyanate (HDI) at the weight ratios of HmSLLAO/HmSDLAO = 1/1 and (HmSLLAO + HmSDLAO)/H3CLO = 100/0, 75/25, 50/50, 25/75 or 0/100). The influence of the arm number on the crystallization behavior, thermal and mechanical properties of SPN-mscLAO/3CLOs were systematically investigated by comparing with those of sugar-alcohol-based homochiral polymer network (SPN-mLLAO, m = 4, 5 or 6) prepared by the reaction of HmSLLAO and HDI. Stereocomplex (sc) crystallites are dominantly formed for SPN-mscLAO/3CLOs 100/0⁻25/75, whereas SPN-mLLAOs were amorphous. The higher order of melting temperature of sc-crystals for SPN-mscLAO/3CLOs 100/0⁻25/75 was m = 5 > m = 6 > m = 4. The sc-crystallinities of SPN-4scLAO/3CLOs 100/0⁻50/50 were significantly lower than those of SPN-mscLAO/3CLOs 100/0⁻50/50 (m = 5 and 6). The larger order of the sc-spherulite size at crystallization temperature of 110 °C was m = 5 > m = 6 > m = 4 for SPN-mscLAO/3CLO 100/0. The size and number of sc-spherulites decreased with increasing crystallization temperature over the range of 110⁻140 °C and with increasing CLO fraction. Among all the networks, SPN-5scLAO/3CLOs 75/25 and 50/50 exhibited the highest and second highest tensile toughnesses (21.4 and 20.3 MJ·m-3), respectively.

Self-healing hydrogels formed by complexation between calcium ions and bisphosphonate-functionalized star-shaped polymers.

Star-shaped poly(ethylene glycol) (PEG) chain termini were functionalized with alendronate to create transient networks with reversible crosslinks upon addition of calcium ions. The gelation ability of alendronate-functionalized PEG was greatly dependent on the number of arms and arm molecular weight. After mixing polymer and calcium solutions, the formed hydrogels could be cut and then brought back together without any visible interface. After 2 minutes of contact, their connection was strong enough to allow for stretching without tearing through the previous fracture surface. Oscillatory rheology showed that the hydrogels recovered between 70 and 100% of the original storage and loss modulus after rupture. Frequency sweep measurements revealed a liquid-like behavior at lower frequencies and solid-like at high frequencies. Shifting frequency curves obtained at different calcium and polymer concentrations, all data collapsed in a single common master curve. This time-concentration superposition reveals a common relaxation mechanism intrinsically connected to the calcium-bisphosphonate complexation equilibrium.

Stereocomplexation in Copolymer Networks Incorporating Enantiomeric Glycerol-Based 3-Armed Lactide Oligomers and a 2-Armed ɛ-Caprolactone Oligomer.

The reactions of enantiomeric glycerol-based 3-armed lactide oligomers (H3DLAO and H3LLAO) and a diethylene glycol-based 2-armed ɛ-caprolactone oligomer (H2CLO) with hexamethylene diisocyanate (HDI) produced polyesterurethane copolymer networks (PEU-3scLAO/2CLOs 100/0, 75/25, 50/50, 25/75 and 0/100) with different feed ratios of stereocomplex (sc) lactide oligomer (H3scLAO = H3DLAO + H3LLAO, H3DLAO/H3LLAO = 1/1) and H2CLO. Thermal and mechanical properties of the copolymer networks were compared with those of a simple homochiral (hc) network (PEU-3DLAO) produced by the reaction of H3DLAO and HDI. X-ray diffraction and differential scanning calorimetric analyses revealed that sc crystallites are formed without any hc crystallization for PEU-3scLAO/2CLOs, and that PEU-3DLAO is amorphous. The melting temperatures of sc crystallites for PEU-3scLAO/2CLOs were much higher than that of hc crystallites of H3DLAO. The polarized optical microscopic analysis revealed that the nucleation efficiency is enhanced with increasing feed of H3scLAO fraction, whereas the spherulite growth rate is accelerated with increasing feed H2CLO fraction over 100/0-50/50 networks. PEU-3scLAO/2CLO 100/0 (i.e., PEU-3scLAO) exhibited a higher tensile strength and modulus than PEU-3DLAO. The elongation at break and tensile toughness for PEU-3scLAO/2CLOs increased with an increasing feed amount of H2CLO.

A Fluorescent Polymer Probe with High Selectivity toward Vascular Endothelial Cells for and beyond Noninvasive Two-Photon Intravital Imaging of Brain Vasculature.

A chromophore-engineering strategy that relies on the introduction of a ground-state distortion in a quadrupolar chromophore was used to obtain a quasi-quadrupolar chromophore with red emission and large two-photon absorption (2PA) cross-section in polar solvents. This molecule was functionalized with water-solubilizing polymer chains. It constitutes not only a remarkable contrast agent for intravital two-photon microscopy of the functional cerebral vasculature in a minimally invasive configuration but presents intriguing endothelial staining ability that makes it a valuable probe for premortem histological staining.

Synthesis and characterization of dendritic star-shaped zwitterionic polymers as novel anticancer drug delivery carriers.

In this work, a novel dendritic star-shaped zwitterionic polymer, polyamidoamine-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (PAMAM-g-PDMAPS), was synthesized. PAMAM dendrimers (generation 2, G2) were firstly prepared and then converted into the PAMAM-Br macroinitiator with 2-bromoisobutyryl bromide for ATRP. Finally, ATRP of zwitterionic DMAPS was carried out to obtain the dendritic star-shaped polymers PAMAM-g-PDMAPS with different PDMAPS chain lengths. Fourier transform-infrared spectroscopy, (1)H NMR, dynamic laser light scattering (DLS), and TEM were used to characterize the polymers. Encapsulation of adriamycin (ADR) by PAMAM-g-PDMAPS nanoparticles and ADR release behavior from ADR-loaded PAMAM-g-PDMAPS nanoparticles were investigated in detail. PAMAM-g-PDMAPS polymers, even starting from low-generation PAMAM core (G2), were found to show high loading efficiency for ADR because ADR existed not only within G2 PAMAM cores but also in PDMAPS layers. The release profile of ADR from ADR-loaded PAMAM-g-PDMAPS nanoparticles was pH-sensitive and could be controlled by the length of PDMAPS chains. Cell viability studies indicated that ADR-loaded PAMAM-g-PDMAPS could effectively restrain the growth of HepG2 cells and even kill them, whereas PAMAM-g-PDMAPS exhibited nontoxicity. All these results demonstrated that dendritic star-shaped zwitterionic polymers PAMAM-g-PDMAPS are attractive candidates as anticancer drug delivery carriers.

Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer.

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ≈25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.