Enhanced Solubility and Bioavailability of Clotrimazole in Aqueous Solutions with Hydrophobized Hyperbranched Polyglycidol for Improved Antifungal Activity.

The poor solubility of clotrimazole in the aqueous medium and the uncontrolled removal of the drug-loaded suppository content limit its effectiveness in the treatment of vulvovaginal candidiasis. We present here the aqueous formulations of clotrimazole in the form of non-Newtonian structured fluids, i.e., Bingham plastic or pseudoplastic fluids constructed of hyperbranched polyglycidol, HbPGL, with a hydrophobized core with aryl groups such as phenyl or biphenyl. The amphiphilic constructs were obtained by the modification of linear units containing monohydroxyl groups with benzoyl chloride, phenyl isocyanate, and biphenyl isocyanate, while the terminal 1,2-diol groups in the shell were protected during the modification step, followed by their deprotection. The encapsulation of clotrimazole within internally hydrophobized HbPGLs using a solvent evaporation method followed by water addition resulted in structured fluids formation. Detailed Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses performed for aryl-HbPGLs with clotrimazole revealed the difference in drug compatibility among polymers. Clotrimazole in biphenyl-enriched HbPGL, unlike phenyl derivatives, was molecularly distributed in both the dry and the hydrated states, resulting in transparent formulations. The shear-thinning properties of the obtained fluid formulations make them injectable and thus suitable for the intravaginal application. Permeability tests performed with the usage of the Franz diffusion cell showed a 5-fold increase in the permeability constant of clotrimazole compared to drugs loaded in a commercially available disposable tablet and a 50-fold increase of permeability in comparison to the aqueous suspension of clotrimazole. Furthermore, the biphenyl-modified HbPGL-based drug liquid showed enhanced antifungal activity against both Candida albicans and Candida glabrata that was retained for up to 7 days, in contrast to the phenyl-HbPGL derivatives and the tablet. With their simple formulation, convenient clotrimazole/biphenyl-HbPGL formulation strategy, rheological properties, and enhanced antifungal properties, these systems are potential antifungal therapeutics for gynecological applications. This study points in the synthetic direction of improving the solubility of poorly water-soluble aryl-enriched pharmaceuticals.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.

Evaluation of Encapsulation Potential of Selected Star-Hyperbranched Polyglycidol Architectures: Predictive Molecular Dynamics Simulations and Experimental Validation.

Polymers, including non-linear copolymers, have great potential in the development of drug delivery systems with many advantages, but the design requires optimizing polymer-drug interactions. Molecular dynamics (MD) simulations can provide insights into polymer-drug interactions for designing delivery systems, but mimicking formulation processes such as drying is often not included in in silico studies. This study demonstrates an MD approach to model drying of systems comprising either hydrophilic tinidazole or hydrophobic clotrimazole drugs with amphiphilic hyperbranched copolyethers. The simulated drying protocol was critical for elucidating drug encapsulation and binding mechanisms. Experimentally, two polymers were synthesized and shown to encapsulate clotrimazole with up to 83% efficiency, guided by interactions with the hydrophobic core observed in simulations. In contrast, tinidazole is associated with surface regions, indicating capacity differences between drug types. Overall, this work highlights MD simulation of the drying process as an important tool for predicting drug-polymer complex behaviour. The modelled formulation protocol enabled high encapsulation efficiency and opened possibilities for the design of delivery systems based on computationally derived binding mechanisms. This demonstrates a computational-experimental approach where simulated drying was integral to elucidating interactions and developing optimized complexes, emphasizing the value of molecular modelling for the development of drug delivery formulations.

Cross-linkable star-hyperbranched unimolecular micelles for the enhancement of the anticancer activity of clotrimazole.

Clotrimazole, a hydrophobic drug routinely used in the treatment of vaginal candidiasis, also shows antitumor activity. However, its use in chemotherapy has been unsuccessful to date due to its low solubility in aqueous media. In this work, new unimolecular micelles based on polyether star-hyperbranched carriers of clotrimazole are presented that can enhance solubility, and consequently the bioavailability, of clotrimazole in water. The amphiphilic constructs consisting of a hydrophobic poly(n-alkyl epoxide) core and hydrophilic corona of hyperbranched polyglycidol were synthesized in a three-step anionic ring-opening polymerization of epoxy monomers. The synthesis of such copolymers, however, was only possible by incorporating a linker to facilitate the elongation of the hydrophobic core with glycidol. Unimolecular micelles-clotrimazole formulations displayed significantly increased activity against human cervical cancer HeLa cells compared to the free drug, along with a weak effect on the viability of the normal dermal microvascular endothelium cells HMEC1. This selective activity of clotrimazole on cancer cells with little effect on normal cells was a result of the fact that clotrimazole targets the Warburg effect in cancer cells. Flow cytometric analysis revealed that the encapsulated clotrimazole significantly blocks the progression of the HeLa cycle in the G0/G1 phase and induces apoptosis. In addition, the ability of the synthesized amphiphilic constructs to form a dynamic hydrogel was demonstrated. Such a gel facilitates the delivery of drug-loaded single-molecule micelles to the affected area, where they can form a continuous, self-healing layer.

Self-Healable, Injectable Hydrogel with Enhanced Clotrimazole Solubilization as a Potential Therapeutic Platform for Gynecology.

Injectable, self-healing hydrogels with enhanced solubilization of hydrophobic drugs are urgently needed for antimicrobial intravaginal therapies. Here, we report the first hydrogel systems constructed of dynamic boronic esters cross-linking unimolecular micelles, which are a reservoir of antifungal hydrophobic drug molecules. The selective hydrophobization of hyperbranched polyglycidol with phenyl units in the core via ester or urethane bonds enabled the solubilization of clotrimazole, a water-insoluble drug of broad antifungal properties. The encapsulation efficiency of clotrimazole increases with the degree of the HbPGL core modification; however, the encapsulation is more favorable in the case of urethane derivatives. In addition, the rate of clotrimazole release was lower from HbPGL hydrophobized via urethane bonds than with ester linkages. In this work, we also revealed that the hydrophobization degree of HbPGL significantly influences the rheological properties of its hydrogels with poly(acrylamide-ran-2-acrylamidephenylboronic acid). The elastic strength of networks (GN) and the thermal stability of hydrogels increased along with the degree of HbPGL core hydrophobization. The degradation of the hydrogel constructed of the neat HbPGL was observed at approx. 40 °C, whereas the hydrogels constructed on HbPGL, where the monohydroxyl units were modified above 30 mol %, were stable above 50 °C. Moreover, the flow and self-healing ability of hydrogels were gradually decreased due to the reduced dynamics of macromolecules in the network as an effect of increased hydrophobicity. The changes in the rheological properties of hydrogels resulted from the engagement of phenyl units into the intermolecular hydrophobic interactions, which besides boronic esters constituted additional cross-links. This study demonstrates that the HbPGL core hydrophobized with phenyl units at 30 mol % degrees via urethane linkages is optimal in respect of the drug encapsulation efficiency and rheological properties including both self-healable and injectable behavior. This work is important because of a proper selection of a building component for the construction of a therapeutic hydrogel platform dedicated to the intravaginal delivery of hydrophobic drugs.

Boronic Acid Esters and Anhydrates as Dynamic Cross-Links in Vitrimers.

Growing environmental awareness imposes on polymer scientists the development of novel materials that show a longer lifetime and that can be easily recycled. These challenges were largely met by vitrimers, a new class of polymers that merges properties of thermoplastics and thermosets. This is achieved by the incorporation of dynamic covalent bonds into the polymer structure, which provides high stability at the service temperature, but enables the processing at elevated temperatures. Numerous types of dynamic covalent bonds have been utilized for the synthesis of vitrimers. Amongst them, boronic acid-based linkages, namely boronic acid esters and boroxines, are distinguished by their quick exchange kinetics and the possibility of easy application in various polymer systems, from commercial thermoplastics to low molecular weight thermosetting resins. This review covers the development of dynamic cross-links. This review is aimed at providing the state of the art in the utilization of boronic species for the synthesis of covalent adaptable networks. We mainly focus on the synthetic aspects of boronic linkages-based vitrimers construction. Finally, the challenges and future perspectives are provided.

Composite Dynamic Hydrogels Constructed on Boronic Ester Cross-Links with NIR-Enhanced Diffusivity.

Dynamic hydrogels with thermosensitive cross-links are highly promising platforms for "on-demand" drug delivery systems. However, there is a problem with triggering a response in their whole volume, which reduces their efficiency. To achieve better thermoresponsiveness, a graphene oxide-filled composite hydrogel based on boronic ester cross-links, composed of hyperbranched polyglycidol, HbPGL, and poly(acrylamide-ran-2-acrylamidephenylboronic acid), poly(AM-ran-2-AAPBA), has been constructed. The homogeneous embedment of graphene oxide (GO) in the network assured near-infrared (NIR)-photothermal response in its bulk due to the rapid light-to-heat conversion. The rate and amplitude of materials response increase with graphene oxide concentration. The temperature of the hydrogel containing graphene oxide at a concentration of 13.2 mg/mL increased from 36.6 to 41 °C in 29 s upon NIR irradiation. The network diffusivity and the extent of its change with temperature can be regulated by the length of the applied boronic acid-based cross-linking agent. The hydrogel constructed on the shorter copolymer (Mn = 23 000 g/mol) displayed a significant increase in diffusivity with temperature. A diffusion ordered NMR study revealed that the diffusion coefficient determined for niacin, a model drug encapsulated in the hydrogel, increased from 6.09 × 10-10 at 25 °C to 1.28 × 10-9 m2/s at 41 °C. In the case of the hydrogel constructed on the longer acrylamide copolymer (Mn = 43 000 g/mol), in which physical entanglements stabilize the network, the change of encapsulated niacin diffusion coefficient was significantly smaller, i.e., from 3.83 × 10-10 at 25 °C to 6.63 × 10-10 m2/s at 41 °C. The possibility of on-demand NIR-regulated diffusivity of the reported boronic ester-based hydrogels makes them promising candidates for controlled drug delivery platforms.

Antimicrobial Polymer-Based Hydrogels for the Intravaginal Therapies-Engineering Considerations.

The review is focused on the hydrogel systems dedicated to the intravaginal delivery of antibacterial, antifungal and anti-Trichomonas vaginalis activity drugs for the treatment of gynaecological infections. The strategies for the enhancement of the hydrophobic drug solubility in the hydrogel matrix based on the formation of bigel systems and the introduction of nano- and microparticles as a drug reservoir are presented. Hydrogel carriers of natural and synthetic pharmacological substances, drug-free systems displaying antimicrobial activity thanks to the hydrogel building elements and systems combining the antimicrobial activity of both drug and polymer building components are distinguished. The design of hydrogels facilitating their administration and proper distribution in the vaginal mucosa and the vagina based on thermoresponsive systems capable of gelling at vaginal conditions and already-cross-linked injectable systems after reaching the yield stress are discussed. In addition, the mechanisms of hydrogel bioadhesion that regulate the retention time in the vagina are indicated. Finally, the prospects for the further development of hydrogel-based drug carriers in gynaecological therapies are highlighted.

Star-Shaped Poly(furfuryl glycidyl ether)-Block-Poly(glyceryl glycerol ether) as an Efficient Agent for the Enhancement of Nifuratel Solubility and for the Formation of Injectable and Self-Healable Hydrogel Platforms for the Gynaecological Therapies.

In this paper, we present novel well-defined unimolecular micelles constructed a on poly(furfuryl glycidyl ether) core and highly hydrophilic poly(glyceryl glycerol ether) shell, PFGE-b-PGGE. The copolymer was synthesized via anionic ring-opening polymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether, respectively. MTT assay revealed that the copolymer is non-cytotoxic against human cervical cancer endothelial (HeLa) cells. The copolymer thanks to furan moieties in its core is capable of encapsulation of nifuratel, a hydrophobic nitrofuran derivative, which is a drug applied in the gynaecology therapies that shows a broad antimicroorganism spectrum. The study shows high loading capacity of the copolymer, i.e., 146 mg of nifuratel per 1 g of copolymer. The load unimolecular micelles were characterized using DLS and TEM microscopy and compared with the reference glyceryl glycerol ether homopolymer sample. The presence of numerous 1,2-diol moieties in the shell of PFGE-b-PGG macromolecules enabled the formation of reversible cross-links with 2-acrylamidephenylboronic acid-based polyacrylamide. The obtained hydrogels were both injectable and self-healable, which was confirmed with a rheological study.

Chemoresponsive polymer systems for selective molecular recognition of organic molecules in biological systems.

Smart polymer materials that respond to a chemical stimulus are applied for the construction of biomedical devices and purification/separation systems. Small organic molecules are a particular type of stimulus. Their abnormal concentration indisputably indicates certain diseases. They are also hazardous environment contaminants. Polymer materials, which structure is selectively changed in the presence of a defined organic compound are promising in view of regulation of certain biomedical functions, as well as in view of chemical detectors construction. This review summarizes the state of the art in the self-assemblies of amphiphilic copolymers and polymer networks sensitive toward organic species, with an emphasis on the reports from the last decade. We focus on the relationship between the selectivity of introduced receptor moieties responsible for the change of material structure, the overall structure of material and its functionality.

Chitosan-polyglycidol complexes to coating iron oxide particles for dye adsorption.

The study sheds light on the interaction between chitosan (Ch) and polyglycidol (PGL) and uses their interpolymer complex in hydrophilic coating of iron oxide particles (M). Preliminary investigations were performed by modeling chitosan and polyglycidol chains interactions using coarse grained beads approximation and molecular dynamics simulations. The results revealed that Ch and PGL chains associate together forming weak strength complexes, which was experimentally confirmed by surface tension, fluorescence and FTIR. The Ch-PGL mixture (C) and sodium dodecylsulfate (S) were used for layer-by-layer preparation of hydrophilic multilayer coatings of M. The successful covering, demonstrated by DLS, Zeta potential, FTIR, EDAX, preserved the particles super-paramagnetic properties. The most stable multilayer nanocomposite (MSCS) efficiently adsorbed methylene blue from water. The Freundlich model fitted well the equilibrium isotherm data, indicating a heterogeneous, multilayer adsorption. Benefiting from both nano-size and magnetic properties, this adsorbent could be an effectively, cheaply and eco-friendly wastewater treatment means.

Glycoluril Clips for the Construction of Chemoresponsive Supramolecular Polymer Networks through Homodimer Cross-Links.

The formation of polymer supramolecular networks exhibiting selective sensitivity toward a narrow class of organic compounds is still a significant challenge within the area of reversibly cross-linked materials. Glycoluril molecular clips are U-shaped molecules, which, besides the ability to undergo self-sorting homodimerization, exhibit selectively high molecular recognition of dihydroxyaromatic species. A glycoluril clip diol was introduced into a polymer backbone by using standard polyurethane chemistry. Immobilization of the molecular clip along the polyurethane macromolecule (Glyc Clip-polyurethane) was shown to preserve the native association properties of the clip. Clip motifs embedded in macromolecules form homodimer cross-links in CHCl3 and the resulting structures have a thermoresponsive character. The strength of homodimerization Khomodimer varies from 7.74 104  l mol-1 at 265 K to 9.47 102  l mol-1 at 315 K. A 30 wt % solution of Glyc Clip-polyurethane undergoes gelation at room temperature and exhibits a constant elastic modulus, approximately 3.1 ⋅ 104  Pa, in the broad investigated frequency range. The obtained organogels exhibit selective chemoresponsive properties in the presence of resorcinol, which was demonstrated with 1 H high-resolution magic-angle-spinning NMR spectroscopy and rheological measurements.

Homodimerization driven self-assembly of glycoluril molecular clips with covalently immobilized poly(ε-caprolactone).

We present an unexpected self-assembly of a glycoluril clip-poly(ε-caprolactone) conjugate in chloroform. The conjugate forms homodimer aggregates due to supramolecular interactions between glycoluril moieties, which was confirmed with MALDI-TOF-ms and 1H NMR. TEM revealed the formation of multilayered nanosized prism-shaped objects resembling tree bark in nature.

Adsorption and covalent binding of fibrinogen as a method for probing the chemical composition of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microsphere surfaces.

We investigated the distribution of polyglycidol and polystyrene on the surface of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microspheres (random distribution or segregated into hydrophilic and hydrophobic patches), using fibrinogen (Fb) as a macromolecular probe. The fibrinogen was adsorbed or covalently attached to the surface of the poly(styrene-co-α-tert-butoxy-ω-vinylbenzyl-polyglycidol) (P(S/PGLy)) microspheres. The P(S/PGLy) particles were prepared by emulsion copolymerization of styrene and α-tert-butoxy-ω-vinylbenzyl-polyglycidol (PGLy) macromonomer initiated with potassium persulfate. The polymerizations yielded P(S/PGLy) particles with various surface fractions of polyglycidol, depending on the amount of added macromonomer and the addition process. In some syntheses, the entire macromonomer amount was added once at the beginning of the polymerization, while in others, the macromonomer was added gradually after the formation of particle seeds from pure polystyrene. XPS studies revealed that the fraction of polyglycidol in the interfacial layer of the microspheres was larger when the entire amount of macromonomer was added at the beginning of the polymerization than when it was added after formation of the polystyrene seeds. Studies of fibrinogen adsorption provided the first evidence of segregation of the hydrophobic (polystyrene) and hydrophilic (polyglycidol) components at the surface of the composite P(S/PGLy) microspheres into patches. The hydrophobic patches are composed mainly of polystyrene. However, they also contain a small amount of polyglycidol chains, making the adsorption of fibrinogen weaker than the adsorption onto the pure polystyrene. Studies of covalent immobilization of fibrinogen on the microspheres via 1,3,5-trichlorotriazine confirmed these findings.

Diffusion-Controllable Biomineralization Conducted In Situ in Hydrogels Based on Reversibly Cross-Linked Hyperbranched Polyglycidol.

We present biocompatible hydrogel systems suitable for biomineralization processes based on hyperbranched polyglycidol cross-linked with acrylamide copolymer bearing carbonyl-coordinated boronic acid. At neutral pH, diol functional groups of HbPGL react with boronic acid of polyacrylamide to generate 3D network in water by the formation of boronic ester cross-links. The dynamic associative/dissociative characteristics of the cross-links makes the network reversible. The presented hydrogels display self-healing properties and are injectable, facilitating gap filing of bone tissue. The 1H HR MAS DOSY NMR studies reveal that acrylamide copolymer plays the role of the network framework, whereas HbPGL macromolecules, due to their compact structure, move between reactive sites of the copolymer. The influence of the copolymer macromolecules entanglements and overall polymer concentrations on macromolecules mobility and stress relaxation processes is investigated. The process of hydrogel biomineralization results from hydrolysis of 1-naphthyl phosphate calcium salt catalyzed by encapsulation in hydrogel alkaline phosphatase. The environment of the hydrogel is entirely neutral toward the enzyme. However, the activity of alkaline phosphatase encapsulated within the hydrogel structure is diffusion-limited. In this article, based on the detailed characteristics of three model hydrogel systems, we demonstrate the influence of the hydrogel permeability on the encapsulated enzyme activity and calcium phosphate formation rate. The 1H HR MAS DOSY NMR is used to monitor diffusion low-molecular weight compound within hydrogels, whereas 31P HR MAS NMR facilitates monitoring of the progress of biomineralization in situ within hydrogels. The results show a direct correlation between low molecular diffusivity in hydrogels and network dynamics. We demonstrate that the morphology of in situ-generated calcium phosphate within three model HbPGL/poly(AM-ran-APBA) hydrogels of different low molecular permeability varies substantially from sparsely deployed large, well-defined crystals to an even distribution within the polymers polycrystalline continuous network.

Spheroidal Microparticle Monolayers Characterized by Streaming Potential Measurements.

An efficient method was developed enabling the synthesis of spheroidal polymer microparticles. Thorough physicochemical characteristics of the particles were acquired comprising the size, shape, electrophoretic mobility, and the diffusion coefficient. The particles were monodisperse, and their shape was well-fitted by prolate spheroids having the axis ratio equal to 4.17. Knowing the diffusion coefficient, their hydrodynamic diameter of 449 nm was calculated, which matched the value derived from Brenner's analytical expression. Particle deposition kinetics on mica and silicon/silica substrates, modified by poly(allylamine hydrochloride) (PAH) adsorption, was studied by optical microscopy and AFM imaging. The validity of the random sequential adsorption model was confirmed. Additionally, monolayers of the particles on these substrates were thoroughly characterized in situ by the streaming potential measurements for different ionic strengths. These measurements confirmed that the ζ potential change with the spheroidal particle coverage is less abrupt than for spheres and agrees with theoretical predictions. Exploiting these results, a useful analytical expression was derived that allows one to calculate the spheroidal particle coverage in situ via the streaming potential measurements. This expression, especially accurate for low coverage range, can be used for a quantitative interpretation of adsorption and desorption kinetics of anisotropic macromolecules, e.g., proteins on solid substrates.

Size-Controlled 3D Colloidal Crystals Formed in an Aqueous Suspension of Polystyrene/Polyglycidol Microspheres with Covalently Bound l-DOPA.

Stable three-dimensional colloidal crystals were fabricated in an aqueous suspension of Tris buffer at pH > 8. The basic building blocks of the crystals were submicron-sized polystyrene-polyglycidol core-shell particles (Dn(SEM) = 270 ± 18 nm) with covalently bound 3,4-dihydroxyphenylalanine (l-DOPA). The growth of the crystals was triggered by a thermodynamically favorable arrangement of particles leading to their close packing and by the formation of covalent cross-links between the individual particles. Under alkaline conditions, molecules of l-DOPA are oxidized, which allows their participation in cross-linking, necessary for the stabilization of the formed colloidal crystals. The average size of the fabricated colloidal crystals is determined by their weight, density of the suspending medium, and the energy of their Brownian motion. Crystals generated during the suspension of particles fall down after reaching the critical weight. Therefore, crystals of similar dimensions are deposited at the bottom of the vessel. The described system is the first example of the formation of stable colloidal crystals in a suspension.

Monolayers of Poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) Microparticles Formed by Controlled Self-Assembly with Potential Application as Protein-Repelling Substrates.

The kinetics of the self-assembly of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microparticles on poly(allylamine hydrochloride)-derivatized silicon/silica substrate was determined by direct AFM imaging and streaming potential (SP) measurements. The kinetic runs acquired under diffusion-controlled transport were quantitatively interpreted in terms of the extended random sequential adsorption (RSA) model. This allowed confirmation of a core/shell morphology of the microparticles. The polyglycidol-rich shell of thickness equal to 25 nm exhibited a fuzzy structure that enabled penetration of particles into each other resulting in high coverage inaccessible for ordinary microparticles. The SP measurements interpreted by using the 3D electrokinetic model confirmed this microparticle structure. Additionally, the acid-base characteristics of the microparticle monolayers were determined for a broad pH range. By using the streaming potential measurements, human serum albumin (HSA) adsorption on the microparticle monolayers was investigated under in situ conditions. It was confirmed that the protein adsorption was considerably lower than for the reference case of bare silicon/silica substrate under the same physicochemical conditions. This effect was attributed to the presence of the shell diminishing the protein/microparticle physical interactions.

Polyglycidol, Its Derivatives, and Polyglycidol-Containing Copolymers-Synthesis and Medical Applications.

Polyglycidol (or polyglycerol) is a biocompatible polymer with a main chain structure similar to that of poly(ethylene oxide) but with a ⁻CH2OH reactive side group in every structural unit. The hydroxyl groups in polyglycidol not only increase the hydrophilicity of this polymer but also allow for its modification, leading to polymers with carboxyl, amine, and vinyl groups, as well as to polymers with bonded aliphatic chains, sugar moieties, and covalently immobilized bioactive compounds in particular proteins. The paper describes the current state of knowledge on the synthesis of polyglycidols with various topology (linear, branched, and star-like) and with various molar masses. We provide information on polyglycidol-rich surfaces with protein-repelling properties. We also describe methods for the synthesis of polyglycidol-containing copolymers and the preparation of nano- and microparticles that could be derived from these copolymers. The paper summarizes recent advances in the application of polyglycidol and polyglycidol-containing polymers as drug carriers, reagents for diagnostic systems, and elements of biosensors.

Gradient Poly(styrene-co-polyglycidol) Grafts via Silicon Surface-Initiated AGET ATRP.

Gradient copolymer grafts of styrene and α-tert-butoxy-ω-vinylbenzyl-poly(glycidol ethoxyethyl ether) (PGLet), a precursor of α-tert-butoxy-ω-vinylbenzyl-polyglycidol macromonomer (PGL), were prepared on silicon wafers via a surface-initiated activator generated by electron transfer radical polymerization (AGET ATRP). Silicon plates with previously attached 2-bromoisobutyrate served as a macroinitiator for the AGET ATRP (activator generated by electron transfer) of styrene and PGLet. The copolymers' gradient P(S-co-PPGL) of composition and thickness was obtained by a simple method where the plates were slowly removed from reaction mixture using a step motor. PGLet was added continuously (dropwise) into the reactor during withdrawal of the plates from solution in order to increase the relative concentration of PGLet in polymerization mixture. A range of strategies of making grafts was tested. The plates with copolymers grafts were analyzed by various techniques, like XPS, ellipsometry, and FTIR spectroscopy. The results indicate that the AGET ATRP process is dependent on the styrene/PGLet macromonomer ratio in the polymerization mixture. Under optimal conditions, the addition of PGLet during polymerization and subsequent deprotection of hydroxyl groups of PGLet permit to obtain plates with a novel copolymer layer with composition, thickness, and wettability gradient. Plates with chemical composition of copolymer grafts gradient served as versatile supports with controlled hydrophilic/hydrophobic area and were suitable for tailored deposition of particles.