Due to their unique properties, such as controlled drug release and improved bioavailability, polymeric microparticles and nanoparticles (MPs and NPs) have gained considerable interest in the pharmaceutical industry. Nevertheless, the high costs associated with biodegradable polymers and the active pharmaceutical ingredients (APIs) used for treating serious diseases, coupled with the vast number of API-polymer combinations, make the search for effective API-polymer MPs and NPs a costly and time-consuming process. In this work, the correlation between the compatibility of selected model APIs (i.e., ibuprofen, naproxen, paracetamol, and indomethacin) with poly(lactide-co-glycolide) (PLGA) derived from respective binary phase diagrams and characteristics of prepared MPs and NPs, such as the drug loading and solid-state properties, was investigated to probe the possibility of implementing the modeling of API-polymer thermodynamic and kinetic phase behavior as part of rational design of drug delivery systems based on MPs and NPs. API-PLGA-based MPs and NPs were formulated using an emulsion-solvent evaporation technique and were characterized for morphology, mean size, zeta potential, drug loading, and encapsulation efficiency. The solid-state properties of the encapsulated APIs were assessed using differential scanning calorimetry and X-ray powder diffraction. The evaluated compatibility was poor for all considered API-PLGA pairs, which is in alignment with the experimental results showing low drug loading in terms of amorphous API content. At the same time, drug loading of the studied APIs in terms of amorphous content was found to follow the same trend as their solubility in PLGA, indicating a clear correlation between API solubility in PLGA and achievable drug loading. These findings suggest that API-polymer phase behavior modeling and compatibility screening can be employed as an effective preformulation tool to estimate optimum initial API concentration for MP and NP preparation or, from a broader perspective, to tune or select polymeric carriers offering desired drug loading.

• Klíčová slova
• Active pharmaceutical ingredient, Compatibility, Drug delivery system, Micro/nano-particle, Phase diagram, Poly(lactide-co-glycolide),
• MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• léčivé přípravky MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   MeSH
• systémy cílené aplikace léků metody   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dilactide MeSH Prohlížeč
• kopolymer kyseliny glykolové a mléčné MeSH
• léčivé přípravky MeSH
• nosiče léků MeSH
• polymery * MeSH

CONTEXT: Rational design of polymeric materials prepared with the molecular imprinting technology is gaining even more space, as it can provide the optimal conditions to direct the laboratory molecularly imprinting polymer (MIP) preparation, maximizing their efficiency while reducing costs and preparation time, when compared to try-and-error approaches. We perform a rational design of an MIP with specific cavities for cercosporin accommodation by means of computational tools. The main steps of an MIP preparation were simulated and it was found that the most appropriated functional monomer to be used in the MIP preparation for cercosporin is the acrylamide, while the most suitable crosslinking agent is found to be p-divinylbenzene. Also, the most suitable solvents to remove cercosporin from the cavity are those with low dielectric constant, such as chloroform. This kind of solvent can then be used in washing step, in the case of use the MIP for sensing destinations. On the other hand, solvents like water, which has high dielectric constants, can efficiently improve the interactions between cercosporin and the functional monomer acrylamide, being indicated when the objective is to attract or maintain the cercosporin inside the MIP cavity. Thus, a MIP@cercosporin hybrid material can be used in aqueous solutions more reliably, or even the cercosporin detection in this media can be favoured. In the selectivity analysis of the material prepared in this specific condition, the results point that this MIP can also detect elsinochrome A with high efficiency, and could be more selective for hypericin, altertoxin, hypocrelin A, and phleichrome mycotoxins. METHOD: The main steps of a MIP synthesis were theoretically simulated trough density functional theory (DFT) calculations aiming to direct and optimize the synthesis and applications of the material before the bench tests. Initially, in order to choose the most suitable functional to be employed for cercosporin calculations, eight of the DFT functionals that had been previously used for cercosporin calculations in literature were tested, which were the LCWPBE, B3LYP, CAM-B3LYP, M062-X, mPW1PW91, PBE0, TPSSh, and ωb97Xd. The theoretical 1H NMR chemical shifts for cercosporin molecule were calculated and compared with experimental results to analyze the performance of the functionals. Of all these, the best results were obtained with the TPSSh functional, employing the 6-31G(d,p) basis set, and this level of theory was then used for all the following steps. All the simulations were performed by means of geometry optimizations and frequency calculations. Additionally, AIM calculations were employed for further analysis of the interactions between the chosen functional monomer and cercosporin template in step 1, which was functional monomer selection. In washing step, the calculations were done using implicit solvation model, and finally, in selectivity tests, the putative "solid" MIP was simulated by freezing the positions of the monomers after the template remotion, and then other structurally similar toxins were placed in its cavity for the geometry optimizations and frequency calculations.

• Klíčová slova
• DFT, Molecularly imprinting technology, Mycotoxins, Theoretical design,
• Publikační typ
• časopisecké články MeSH

The integration of 3D printing into the pharmaceutical sciences opens new possibilities for personalized medicine. Poly(lactide) (PLA), a biodegradable and biocompatible polymer, is highly suitable for biomedical applications, particularly in the context of 3D printing. However, its processability often requires the addition of plasticizers. This study investigates the use of phase diagram modeling as a tool to guide the rational selection of plasticizers and to assess their impact on the thermodynamic and kinetic stability of PLA-based amorphous solid dispersions (ASDs) containing active pharmaceutical ingredients (APIs). Thermodynamic stability against API recrystallization was predicted based on the API solubility in PLA and Plasticizer-PLA carriers using the Conductor-like Screening Model for Real Solvents (COSMO-RS), while the kinetic stability of the ASDs was evaluated by modeling the glass transition temperatures of the mixtures. Two APIs, indomethacin (IND) and naproxen (NAP), with differing glass-forming abilities (i.e., recrystallization tendencies), and three plasticizers, triacetin (TA), triethyl citrate (TEC), and poly(L-lactide-co-caprolactone) (PLCL), were selected for investigation. The physical stability of ASD formulations containing 9 wt% API and plasticizer to PLA in two ratios, 10:81 and 20:71 w/w %, was monitored over time using differential scanning calorimetry and X-ray powder diffraction and compared with phase diagram predictions. All formulations were predicted to be thermodynamically unstable; however, those containing no plasticizer or with TEC and TA at 10 wt% were predicted to exhibit some degree of kinetic stability. Long-term physical studies corroborated these predictions. The correlation between the predicted phase behavior and long-term physical stability highlights the potential of phase diagram modeling as a tool for the rational design of ASDs in pharmaceutical 3D printing.

• Klíčová slova
• 3D printing, Active pharmaceutical ingredient, Amorphous solid dispersion, COSMO-RS, PLA, Personalized medicine, Phase diagram, Plasticizers,
• MeSH
• 3D tisk * MeSH
• chemie farmaceutická metody   MeSH
• citráty chemie   MeSH
• diferenciální skenovací kalorimetrie metody   MeSH
• farmaceutická technologie metody   MeSH
• indomethacin * chemie   MeSH
• krystalizace MeSH
• naproxen chemie   MeSH
• polyestery * chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost * MeSH
• stabilita léku MeSH
• termodynamika MeSH
• tranzitní teplota MeSH
• triacetin chemie   MeSH
• zvláčňovadla * chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• citráty MeSH
• ethyl citrate MeSH Prohlížeč
• indomethacin * MeSH
• naproxen MeSH
• poly(lactide) MeSH Prohlížeč
• polyestery * MeSH
• rozpouštědla MeSH
• triacetin MeSH
• zvláčňovadla * MeSH

The quantum mechanics-aided COSMO-SAC activity coefficient model is applied and systematically examined for predicting the thermodynamic compatibility of drugs and polymers. The drug-polymer compatibility is a key aspect in the rational selection of optimal polymeric carriers for pharmaceutical amorphous solid dispersions (ASD) that enhance drug bioavailability. The drug-polymer compatibility is evaluated in terms of both solubility and miscibility, calculated using standard thermodynamic equilibrium relations based on the activity coefficients predicted by COSMO-SAC. As inherent to COSMO-SAC, our approach relies only on quantum-mechanically derived σ-profiles of the considered molecular species and involves no parameter fitting to experimental data. All σ-profiles used were determined in this work, with those of the polymers being derived from their shorter oligomers by replicating the properties of their central monomer unit(s). Quantitatively, COSMO-SAC achieved an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data. Qualitatively, COSMO-SAC correctly categorized different polymer types in terms of their compatibility with drugs and provided meaningful estimations of the amorphous-amorphous phase separation. Furthermore, we analyzed the sensitivity of the COSMO-SAC results for ASD to different model configurations and σ-profiles of polymers. In general, while the free volume and dispersion terms exerted a limited effect on predictions, the structures of oligomers used to produce σ-profiles of polymers appeared to be more important, especially in the case of strongly interacting polymers. Explanations for these observations are provided. COSMO-SAC proved to be an efficient method for compatibility prediction and polymer screening in ASD, particularly in terms of its performance-cost ratio, as it relies only on first-principles calculations for the considered molecular species. The open-source nature of both COSMO-SAC and the Python-based tool COSMOPharm, developed in this work for predicting the API-polymer thermodynamic compatibility, invites interested readers to explore and utilize this method for further research or assistance in the design of pharmaceutical formulations.

• Klíčová slova
• COSMO-SAC, amorphous solid dispersions (ASD), drug−polymer thermodynamic compatibility, miscibility, prediction, quantum mechanics, solubility,
• MeSH
• chemie farmaceutická metody   MeSH
• léčivé přípravky chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   MeSH
• rozpustnost * MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• léčivé přípravky MeSH
• nosiče léků MeSH
• polymery * MeSH

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

• Klíčová slova
• LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
• MeSH
• myši MeSH
• polymery * MeSH
• teplota MeSH
• tkáňová distribuce MeSH
• uvolňování léčiv MeSH
• voda * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• polymery * MeSH
• voda * MeSH

A styrene-butadiene-styrene co-polymer matrix nanocomposite filled with graphene nanoplatelets was studied to prepare chemiresistive volatile organic compounds (VOCs) room temperature sensors with considerable response and selectivity. Nanofiller concentration was estimated from the electrical conductivity percolation behaviour of the nanocomposite. Fabricated sensors provided selective relative responses to representative VOCs differing by orders of magnitude. Maximum observed average relative responses upon exposure to saturated vapours of the tested VOCs were ca. 23% for ethanol, 1600% for acetone, and the giant values were 9 × 106% for n-heptane and 10 × 106% for toluene. The insensitivity of the sensor to the direct saturated water vapour exposure was verified. Although high humidity decreases the sensor's response, it paradoxically enhances the resolution between hydrocarbons and polar organics. The non-trivial sensing mechanism is explained using the Hansen solubility parameters (HSP), enabling a rational design of new sensors; thus, the HSP-based class of sensors is outlined.

• Klíčová slova
• Hansen solubility parameter, chemiresistivity, co-polymer, graphene, organic vapour sensing, sensor,
• Publikační typ
• časopisecké články MeSH

Boron-rich particles with the boron fraction ca.10-20 wt % of controllable shape and size that can be easily prepared via simple ion co-assembly are promising material for tumor treatment by boron neutron capture therapy. Electroneutral, dynamic core-shell polymeric nanoparticles were prepared by co-assembly of cationic PEO-block-PGEA diblock copolymer with sodium closo-dodecaborate, Na2 [B12 H12 ]. This is the first example of polymer nanoparticles based on [B12 H12 ]2- nano-ion pairing. The high [B12 H12 ]2- loading is proven by calorimetry at physiological salt concentration. As a result of rational design, rod-, worm- and sphere-like particles were produced and further tested using human glioblastoma and cervical carcinoma cell lines. Rod-like particles yielded the highest internalization capability in all tested cell lines.

• Klíčová slova
• boron cluster compounds, boron neutron capture therapy, nano-ions, polymer nanoparticles, self-assembly,
• Publikační typ
• časopisecké články MeSH

In this present investigation, aluminium (Al3+) fabricated 2-aminobenzene-1,4-dicarboxylic acid (ABDC) namely Al@ABDC metal organic frameworks (MOFs) was developed for defluoridation studies. The unique advantages of developed MOFs possess high selectivity, high porosity and enhanced surface area but the developed powder form of Al@ABDC MOFs has several limitations in field applications like slow filtration and column blockage. To prevail over these troubles, biopolymer namely chitosan (CS) supported Al@ABDC MOFs namely Al@ABDC-CS beads were developed for effective fluoride adsorption from water. The synthesized Al@ABDC-CS beads were employed for the retention of fluoride in batch level. The defluoridation capacities (DCs) of Al@ABDC MOFs and Al@ABDC-CS beads were found to be 4880 and 4900 mgF- kg-1 respectively. The influencing parameters of adsorption method namely agitation time, adsorbent dosage, initial fluoride concentration, pH, co-existing anions and temperature were exploit to get utmost defluoridation capacity (DC) of Al@ABDC-CS beads. The experimental data of Al@ABDC-CS beads have been evaluated utilizing Langmuir, Fruendlich and Dubinin-Radushkevich (D-R) isotherms. The defluoridation nature of Al@ABDC-CS beads was determined by the thermodynamic parameters. The order of reaction of Al@ABDC-CS beads was studied using various kinetic models. The regeneration and field water studies of Al@ABDC-CS beads were also carried out to check their reusability and suitability at field conditions.

• Klíčová slova
• Aluminium, Chitosan, Defluoridation, Field study, Metal organic frameworks, Regeneration,
• MeSH
• adsorpce MeSH
• chemické látky znečišťující vodu * MeSH
• chitosan * MeSH
• fluoridy MeSH
• hliník MeSH
• kinetika MeSH
• koncentrace vodíkových iontů MeSH
• porézní koordinační polymery * MeSH
• termodynamika MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chemické látky znečišťující vodu * MeSH
• chitosan * MeSH
• fluoridy MeSH
• hliník MeSH
• porézní koordinační polymery * MeSH
• voda MeSH

A substantial development in nanoscale materials possessing catalytic activities comparable with natural enzymes has been accomplished. Their advantages were owing to the excellent sturdiness in an extreme environment, possibilities of their large-scale production resulting in higher profitability, and easy manipulation for modification. Despite these advantages, the main challenge for artificial enzyme mimetics is the lack of substrate selectivity where natural enzymes flourish. This review addresses this vital problem by introducing substrate selectivity strategies to three classes of artificial enzymes: molecularly imprinted polymers, nanozymes (NZs), and DNAzymes. These rationally designed strategies enhance the substrate selectivity and are discussed and exemplified throughout the review. Various functional mechanisms associated with applying enzyme mimetics in biosensing and bioassays are also given. Eventually, future directives toward enhancing the substrate selectivity of biomimetics and related challenges are discussed and evaluated based on their efficiency and convenience in biosensing and bioassays.

• Klíčová slova
• Artificial-enzyme mimetics, DNAzymes, Enhanced selectivity, Molecularly-imprinted-polymer, Nanozymes,
• MeSH
• biomimetické materiály * chemie   MeSH
• biosenzitivní techniky * metody   MeSH
• biotest * MeSH
• DNA katalytická chemie   metabolismus   MeSH
• enzymy metabolismus   chemie   MeSH
• lidé MeSH
• molekulárně imprintované polymery chemie   MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA katalytická MeSH
• enzymy MeSH
• molekulárně imprintované polymery MeSH

Crystalline and amorphous organic materials are an emergent class of heterogeneous photocatalysts for the generation of hydrogen from water, but a direct correlation between their structures and the resulting properties has not been achieved so far. To make a meaningful comparison between structurally different, yet chemically similar porous polymers, two porous polymorphs of a triazine-based graphdiyne (TzG) framework are synthesized by a simple, one-pot homocoupling polymerization reaction using as catalysts CuI for TzGCu and PdII /CuI for TzGPd/Cu . The polymers form through irreversible coupling reactions and give rise to a crystalline (TzGCu ) and an amorphous (TzGPd/Cu ) polymorph. Notably, the crystalline and amorphous polymorphs are narrow-gap semiconductors with permanent surface areas of 660 m2 g-1 and 392 m2 g-1 , respectively. Hence, both polymers are ideal heterogeneous photocatalysts for water splitting with some of the highest hydrogen evolution rates reported to date (up to 972 μmol h-1 g-1 with and 276 μmol h-1 g-1 without Pt cocatalyst). Crystalline order is found to improve delocalization, whereas the amorphous polymorph requires a cocatalyst for efficient charge transfer. This will need to be considered in future rational design of polymer catalysts and organic electronics.

• Klíčová slova
• carbon, covalent organic frameworks, photocatalysis, porous polymers, semiconductors,
• Publikační typ
• časopisecké články MeSH