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

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

Preparation and optical properties of novel bioactive photonic crystals obtained from core-shell poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microspheres

Optical properties of polymer microspheres with polystyrene cores and polyglycidol-enriched shells poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) (P(S/PGL) particles with number average diameters Dn determined by scanning electron microscopy equal 237 and 271 nm), were studied before and after immobilization of ovalbumin. The particles were synthesized by emulsifier-free emulsion copolymerization of styrene and polyglycidol macromonomer (poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol)) initiated with potassium persulfate. Molar fraction of polyglycidol units in the interfacial layer of the microspheres determined by XPS was equal 42.6 and 34.0%, for the particles with Dn equal 137 and 271 nm, respectively. Colloidal crystals from the aforementioned particles were prepared by deposition of particle suspensions on the glass slides and subsequent evaporation of water. It was found that optical properties of colloidal crystals from the P(S/PGL) microspheres strongly depend on modification of their interfacial layer by covalent immobilization of ovalbumin. The coating of particles with ovalbumin resulted in decreasing their refractive index from 1.58 to 1.52

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

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

Converting raw birch suberin into vitrimer

<p>The xlsx file contains numeric data for figures that were included in the paper entitled "Converting raw birch suberin into vitrimer"</p><p>These include:</p><ol><li>Flow curve of suberin resin</li><li>DSC of suberin resin</li><li>Rheometric curves of suberin resin in the presence of various catalysts </li><li>The influence of a catalyst on suberin thermoset stress relaxation</li><li>The influence of DBTDL concentration on suberin thermoset stress relaxation</li><li>The influence of temperature on suberin thermoset stress relaxation</li><li>Creep-recovery of suberin vitrimer</li><li>Stress relaxation of repolymerized suberin vitrimer </li><li>TGA of suberin vitrimer</li><li>DSC of raw and recycled suberin vitrimer</li><li>Mechanical performance of raw and recycled suberin vitrimer</li><li>Amplitude sweep test of suberin vitrimer</li><li>Frequency sweep test of suberin vitrimer</li><li>DMTA data of suberin vitrimer</li><li>1H NMR Data of suberin resin</li><li>Hydrolytic degradation data of suberin vitrimer</li><li>Soil degradation data of suberin vitrimer</li></ol&gt

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-<i>ran</i>-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

Temperature-Induced Changes in the Nanostructure of Hydrogels Based on Reversibly Cross-Linked Hyperbranched Polyglycidol with B(OH)₄^⊖ Ions

Solid-state boron nuclear magnetic resonance (¹¹B NMR) and positron annihilation lifetime spectroscopies (PALS) were used to study the molecular structure of self-healing hydrogels based on cross-linked hyperbranched polyglycidol (HbPGL) with borax at basic pH. The lifetime and intensity of orthopositronium allowed characterizing the micro- and nanostucture of hydrogels at various thermal conditions. Stepwise changes in the free volume parameters were found in pure HbPGL as well as in hydrogels based on this polymer. However, the shift in the phase transition temperature suggests that the important properties of the hydrogel arise from the water building these systems. Rheological measurements demonstrated the subsequent reduction of the average cross-link lifetime within the polymer network under heating. Composition of boronic species within hydrogel systems also diverged upon change in temperature range from −10 °C to +70 °C. The reduced fraction of boronic diester upon heating was quantitatively rebuilt after cooling to ambient temperature. Heating the hydrogel at 70 °C launched the irreversible release of a small fraction of HbPGL macromolecules from the polymer network, generating its defects, still present after cooling. The structural studies carried out in a nanoscale facilitated the distinction in cross-linking density of two analyzed hydrogel systems. The PAL spectroscopy turned out to be a valuable tool to exclude entanglements between individual macromolecules of pristine HbPGL

Converting Unrefined Birch Suberin Monomers into Vitrimer

Suberin extracted from birch bark, a side product of the wood industry, was used as a resin for the synthesis of a biobased vitrimer utilizing the transesterification reaction. Suberin was extracted by hydrolyzing the outer bark of birch trees under alkaline conditions and used further without refining. The resulting resin, natively rich in hydroxyl and carboxyl groups, was polymerized in the presence of various catalysts and a small-molecule polyol to provide an excess of primary OH groups. The study showed that among the catalysts tested, only dibutyltin dilaurate (DBTDL) promoted the transesterification reaction in the polymer matrix to the extent that the polymer could be recycled at elevated temperatures. Furthermore, a chemical recycling route was successfully tested through alkaline hydrolysis and repolymerization of the obtained vitrimer. The resulting suberin vitrimer showed elastomer-like properties with Tg at approximately −20 °C and a Young’s modulus exceeding 1 MPa. It was also demonstrated to be hydrolytically stable under moderately alkaline and acidic conditions

Monolayers of Poly(styrene/α-<i>tert</i>-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-<i>tert</i>-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