RESUMEN
Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.
Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Retículo Endoplásmico , Proteínas de la Membrana , ATPasas Tipo P , Pliegue de Proteína , Humanos , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/química , Retículo Endoplásmico/metabolismo , Células HEK293 , Interacciones Hidrofóbicas e Hidrofílicas , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/química , Dominios Proteicos , Procesamiento Proteico-Postraduccional , ATPasas de Translocación de Protón/metabolismo , ATPasas de Translocación de Protón/genética , ATPasas de Translocación de Protón/química , ATPasas Tipo P/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/química , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismoRESUMEN
Small hydrophobic (SH) proteins are a class of viral accessory proteins expressed by many members of the negative-stranded RNA viral families Paramyxoviridae and Pneumoviridae. Identified SH proteins are type I or II transmembrane (TM) proteins with a single-pass TM domain. Little is known about the functions of SH proteins; however, several possess viroporin activity, enhancing membrane permeability of infected cells or those expressing SH protein. Moreover, several SH proteins inhibit apoptosis and immune signaling pathways within infected cells, including TNF and interferon signaling, or activate inflammasomes. SH proteins are generally nonessential for viral replication in vitro, but loss of SH is often associated with reduced replication in vivo, suggesting a role in enhancing viral replication or evading host immunity. Analogous proteins are expressed by a variety of pathogens of public health importance; thus, understanding the functional importance and mechanisms of SH proteins provides insight into the pathogenesis and replication of negative-sense RNA viruses.
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The long-term value of efficient antigen discovery includes gaining insights into the variety of potential cancer neoantigens, effective vaccines lacking adverse effects, and adaptive immune receptor (IR) targets for blocking adaptive IR-antigen interactions in autoimmunity. While the preceding goals have been partially addressed via big data approaches to HLA (human leukocyte antigen)-epitope binding, there has been little such progress in the big data setting for adaptive IR-epitope binding. This delay in progress for the latter is likely due to, among other things, the much more complicated adaptive IR repertoire in an individual compared to individual HLA alleles. Thus, results described here represent the application of an algorithm for efficient assessment of immunoglobulin heavy chain complementarity determining region-3 (IGH CDR3)-gliadin epitope interactions, with a focus on epitopes known to be associated with an immune response in celiac disease. The hydrophobic, chemical complementarity between celiac case IGH CDR3s and known celiac epitopes was found to be greater in comparison to the hydrophobic, chemical complementarity between the same celiac case IGH CDR3s and a series of control epitopes. Thus, the approaches indicated here likely offer guidance for the development of conveniently applied algorithms for antigen verification and discovery.
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Enfermedad Celíaca , Regiones Determinantes de Complementariedad , Gliadina , Cadenas Pesadas de Inmunoglobulina , Humanos , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/genética , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , Regiones Determinantes de Complementariedad/química , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/inmunología , Gliadina/inmunología , Gliadina/química , Epítopos/inmunología , AlgoritmosRESUMEN
Lipids and nucleic acids are two of the most abundant components of our cells, and both molecules are widely used as engineering materials for nanoparticles. Here, we present a systematic study of how hydrophobic modifications can be employed to modulate the DNA/lipid interface. Using a series of DNA anchors with increasing hydrophobicity, we quantified the capacity to immobilize double-stranded (ds) DNA to lipid membranes in the liquid phase. Contrary to electrostatic effects, hydrophobic anchors are shown to be phase-independent if sufficiently hydrophobic. For weak anchors, the overall hydrophobicity can be enhanced following the concept of multivalency. Finally, we demonstrate that structural flexibility and anchor orientation overrule the effect of multivalency, emphasizing the need for careful scaffold design if strong interfaces are desired. Together, our findings guide the design of tailored DNA/membrane interfaces, laying the groundwork for advancements in biomaterials, drug delivery vehicles, and synthetic membrane mimics for biomedical research and nanomedicine.
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Realizing room-temperature, efficient, and reversible fluoride-ion redox is critical to commercializing the fluoride-ion battery, a promising post-lithium-ion battery technology. However, this is challenging due to the absence of usable electrolytes, which usually suffer from insufficient ionic conductivity and poor (electro)chemical stability. Herein we report a water-in-salt (WIS) electrolyte based on the tetramethylammonium fluoride salt, an organic salt consisting of hydrophobic cations and hydrophilic anions. The new WIS electrolyte exhibits an electrochemical stability window of 2.47 V (2.08-4.55 V vs Li+/Li) with a room-temperature ionic conductivity of 30.6 mS/cm and a fluoride-ion transference number of 0.479, enabling reversible (de)fluoridation redox of lead and copper fluoride electrodes. The relationship between the salt property, the solvation structure, and the ionic transport behavior is jointly revealed by computational simulations and spectroscopic analysis.
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In this study, a database of the thermal stability of collagens and their synthetic analogues has been compiled taking into account literature sources. In total, our database includes 1200 records. As a result of a comparative theoretical analysis of the collected experimental data, the relationship between the melting temperature (Tm) or denaturation temperature (Td) of collagens and the fraction of hydrophobic residues (f) in their molecules has been established. It is shown that this relationship is linear: the larger the f value, the higher the denaturation or melting temperature of a given collagen.
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Screening a library of 1,200 preselected kinase inhibitors for anti-human rhinovirus 2 (HRV-2) activity in HeLa cells identified a class of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) as effective virus blockers. These were based on the 4-anilinoquinazoline-7-oxypiperidine scaffold, with the most potent representative AZ5385 inhibiting the virus with EC50 of 0.35 µM. Several structurally related analogs confirmed activity in the low µM range, while interestingly, other TKIs targeting EGFR lacked anti-HRV-2 activity. To further probe this lack of association between antiviral activity and EGFR inhibition, we stained infected cells with antibodies specific for activated EGFR (Y1068) and did not observe a dependency on EGFR-TK activity. Instead, consecutive passages of HRV-2 in HeLa cells in the presence of a compound and subsequent nucleotide sequence analysis of resistant viral variants identified the S181T and T210A alterations in the major capsid VP1 protein, with both residues located in the vicinity of a known hydrophobic pocket on the viral capsid. Further characterization of the antiviral effects of AZ5385 showed a modest virus-inactivating (virucidal) activity, while anti-HRV-2 activity was still evident when the inhibitor was added as late as 10 h post infection. The RNA copy/infectivity ratio of HRV-2 propagated in AZ5385 presence was substantially higher than that of control HRV indicating that the compound preferentially targeted HRV progeny virions during their maturation in infected cells. Besides HRV, the compound showed anti-respiratory syncytial virus activity, which warrants its further studies as a candidate compound against viral respiratory infections.
Asunto(s)
Rhinovirus , Humanos , Rhinovirus/química , Rhinovirus/genética , Células HeLa , Proteínas de la Cápside , Antivirales/química , Receptores ErbBRESUMEN
Poly(3,4-ethylenedioxythiophene) (PEDOT), particularly in its complex form with poly(styrene sulfonate) (PEDOT:PSS), stands out as a prominent example of an organic conductor. Renowned for its exceptional conductivity, substantial light transmissibility, water processability, and remarkable flexibility, PEDOT:PSS has earned its reputation as a leading conductive polymer. This study explores the unique effects of two additives, Bisphenol A diglycidyl ether (DGEBA) and Dimethyl sulfoxide (DMSO), on the PSS component of PEDOT:PSS films are shown. Both additives induce grain size growth, while DGEBA makes the PEDOT:PSS layer hydrophobic, which acts as a passivation to protect the perovskite layer, which is vulnerable to moisture. The other additive, DMSO, separates the PSS groups, resulting in increased conductivity through the free movement of holes. With these multi-modified p-type PEDOT:PSS, the ITO/M-PEDOT:PSS/Perovskite/PCBM/Ag structured reverse structure solar cell has improved the power conversion efficiency (PCE) from 15.28% to 17.80% compared to the control cell with conventional PEDOT:PSS. It also maintains 90% for 500 h at 60 °C and 300 h at 1 sun illuminating conditions.
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Eumelanin, a natural, biocompatible, and biodegradable photothermal agent derived from biomass, has attracted increasingly considerable attention due to its outstanding photothermal conversion efficiency. Unfortunately, its tendency to aggregate in flexible non-polar polymers, owing to its abundant polar groups on the surface, severely restricted the application of eumelanin in photothermal composite field. Herein, a feasible strategy is proposed to disperse eumelanin in non-polar rubber matrix via in situ generation of Zinc dimethacrylate (ZDMA). The graft-polymerization of ZDMA promotes the interfacial compatibility between styrene butadiene rubber (SBR) and eumelanin, achieving a uniform dispersion of eumelanin in SBR. The rubber composite exhibits a considerable tensile strength of 11.4 MPa, acceptable elongation at break of 146%, and outstanding photothermal conversion efficiency of up to 75.2% with only 1 wt% of eumelanin. Furthermore, based on the easy-processing of SBR matrix, the composite is treated with a sandpaper template technique and sprayed with trimethoxy(1H,1H,2H,2H-perfluorodecyl)silane (PFDTMS) to endow the material with near superhydrophobicity (water contact angle of 147.9°) capacity. Hydrophobicity provides excellent icing resistance, with droplet surfaces extending more than twice as long to freeze. Moreover, this hydrophobic photothermal material exhibits remarkable anti-frosting, de-frosting, and de-icing capabilities.
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Molecular self-assembly has attracted much attention as a potential approach for fabricating nanostructured functional materials. To date, energy-efficient fabrication of nano-objects such as nanofibers, nanorings, and nanotubes is achieved using well-designed self-assembling molecules. However, the application of molecular self-assembly to industrial manufacturing processes remains challenging because regulating the positions and directions of self-assembled products is difficult. Non-covalent molecular assemblies are also too fragile to allow mechanical handling. The present work demonstrates the macroscopic alignment of self-assembled molecular fibers using compression. Specifically, the macroscopic bundling of self-assembled nanofibers is achieved following dispersion in water. These fiber bundles can also be chemically crosslinked without drastic changes in morphology via trialkoxysilyl groups. Subsequently, vertically oriented porous membranes can be produced rapidly by slicing the bundles. This technique is expected to be applicable to various functional self-assembled fibers and can lead to the development of innovative methods of producing anisotropic nanostructured materials.
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Hydrophobic polymer plates with smooth and rough surfaces are used as a stabilizer for cubic liquid marbles (LMs) to study the effect of surface roughness on their formation. The smooth and rough polymer plates can stabilize LMs using liquids with surface tensions of 72.8-26.6 and 72.8-22.9 mN m-1, respectively. It is clarified that the higher the surface roughness, the lower the surface tension of the liquids are stabilized to form the LMs. These results indicated that the introduction of surface roughness improves the hydrophobicity of the polymer plates and the rough polymer plates can stabilize LMs using liquids with a wider surface tension range. Electron microscopy studies and numerical analyses confirmed that the LMs can be formed, when the Cassie-Baxter wetting state, where θY>90° (θY: the contact angle on smooth surfaces) and θR>90° (θR: the contact angle on rough surfaces), and the metastable Cassie-Baxter wetting state, where θY<90° and θR>90°, are realized. Finally, the synthesis of cubic polymer particles are succeeded by free radical polymerization of the cubic LMs containing a hydrophobic vinyl monomer (dodecyl acrylate) in a solvent-free manner.
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Thermoresponsive nanogels (tNGs) are promising candidates for dermal drug delivery. However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, ß-cyclodextrins (ß-CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG-ßCD) to fabricate ßCD-tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of ßCD-tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG-ßCD, as well as the monomer composition of ßCD-tNGs. The outcome reveals that ßCD-tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120 µg mL-1 and augmenting its dermal penetration up to 3.33 µg cm-2. Notably, the acrylation degree of hPG-ßCD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of ßCD-tNGs. Taken together, the introduction of the functionalized ß-CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.
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Glicerol , Interacciones Hidrofóbicas e Hidrofílicas , Nanogeles , Polímeros , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Glicerol/química , Nanogeles/química , Polímeros/química , Animales , Polietileneimina/química , Reactivos de Enlaces Cruzados/química , Temperatura , Absorción Cutánea , Piel/metabolismo , Polietilenglicoles/química , OxazinasRESUMEN
This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P octanol/water and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG-SEDDS in size, stability, and log D SEDDS/release medium. Oral IG bioavailability in PG/ZW-SEDDS and PEG-SEDDS is evaluated in rats. Among the various counterions studied, IG-BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW-SEDDS and PEG-SEDDS have similar ≈40 nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50 mM phosphate buffer pH 6.8. PG/ZW-SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG-SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG-free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.
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Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Péptidos , Polietilenglicoles , Polietilenglicoles/química , Sistemas de Liberación de Medicamentos/métodos , Administración Oral , Animales , Péptidos/química , Péptidos/farmacocinética , Emulsiones/química , Ratas , Masculino , Ratas Sprague-Dawley , Tensoactivos/química , Glicerol/química , Glicerol/análogos & derivadosRESUMEN
All weather, high-efficiency, energy-saving anti-icing/de-icing materials are of great importance for solving the problem of ice accumulation on outdoor equipment surfaces. In this study, a composite material with energy storage, active electro-/photo-thermal de-icing and passive super-hydrophobic anti-icing properties is proposed. Fluorinated epoxy resin and MWCNTs/PTFE particles are used to prepare the top multifunctional anti-icing/de-icing layer, which exhibited super-hydrophobicity with water contact angle greater than 155° and conductivity higher than 69 S m-1. The super-hydrophobic durability of the top layer is verified through tape peeling and sandpaper abrasion tests. The surface can be heated by applying on voltage or light illumination, showing efficient electro-/photo-thermal and all-day anti-icing/de-icing performance. The oleogel material at the bottom layer is capable to absorb energy during heating process and release it during cooling process by phase transition, which greatly delayed the freezing time and saved energy. The icing test of single ice droplet, electro-/photo-thermal de-icing and defrosting tests also proved the high efficiency and energy saving of the anti-icing/de-icing strategy. This study provided a new way to manufacture multi-functional materials for practical anti-icing/de-icing applications.
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Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.
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Péptidos Antimicrobianos , Venenos de Escorpión , Venenos de Escorpión/química , Venenos de Escorpión/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Animales , Humanos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Interacciones Hidrofóbicas e Hidrofílicas , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , TermodinámicaRESUMEN
Clathrate hydrates are among the most intensively studied H-bond inclusion compounds. Despite the broad definition for this class of compounds, their meaning commonly refers to closed polyhedral nanocages that encapsulate small guest molecules. On the other hand, larger solutes enforce another type of encapsulation because of the solute size effect. Herein, we report a series of structures containing various molecules encapsulated by intercalated water layers constructed of polycyclic moieties of L4(4)8(8) topology. We parametrized the corrugation of individual layers and characterized interactions governing their formation. We suggested that these could be categorized as two-dimensional clathrates based on the character of intra-layer interactions and the effects observed between entrapped molecules and water-based intercalators.
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Liposomal vesicles tend to fuse and aggregate during lyophilization. To avoid these events, cryoprotectants are added to the dispersion before lyophilization. Herein, we have compared the effect of three commonly used cryoprotectants (mannitol, MTL; trehalose, THL; and ß-cyclodextrin, ß-CD) upon structural characteristics of liposomes. The formulation was prepared using ethanol injection method, and cryoprotectants were tested at three dose levels (2, 6, and 10 mM). We have elucidated their effect on soy lecithin (SL) liposomes formulated with and without cholesterol (CHL). Characterizations were performed using scattering, thermal, and spectroscopic techniques. CHL molecules interacted hydrophobically with the SL bilayer. In spite of triggering a noticeable increase in the hydrodynamic diameter (about 30 nm), CHL promoted the stabilization of vesicles. Hydrogen bonding interactions were verified by the shift in -OH stretching over 3300-3500 cm-1. This manifested in an increased phase transition temperature (Tm) of SL liposomes. Tm increased further upon incorporation of cryoprotectants, particularly with ß-CD. Enthalpic changes were indicative of an affinity interaction between phospholipids and cryoprotectants, regardless of the presence of CHL. ß-CD showed concentration-dependent changes in the energetics of this interaction. The affinity of cryoprotectant-liposome interaction has been ranked as ß-CD â« THL > MNT.
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Liposomas , Azúcares , Química Farmacéutica , Fosfolípidos , Colesterol/químicaRESUMEN
Lobeline (LOB), a naturally occurring alkaloid, has a broad spectrum of pharmacological activities and therapeutic potential, including applications in central nervous system disorders, drug misuse, multidrug resistance, smoking cessation, depression, and epilepsy. LOB represents a promising compound for developing treatments in various medical fields. However, despite extensive pharmacological profiling, the biophysical interaction between the LOB and proteins remains largely unexplored. In the current article, a range of complementary photophysical and cheminformatics methodologies were applied to study the interaction mechanism between LOB and the carrier protein HSA. Steady-state fluorescence and fluorescence lifetime experiments confirmed the static-quenching mechanisms in the HSA-LOB system. "K" (binding constant) of the HSA-LOB system was determined to be 105 M-1, with a single preferable binding site in HSA. The forces governing the HSA-LOB stable complex were analyzed by thermodynamic parameters and electrostatic contribution. The research also investigated how various metal ions affect complex binding. Site-specific binding studies depict Site I as probable binding in HSA by LOB. We conducted synchronous fluorescence, 3D fluorescence, and circular dichroism studies to explore the structural alteration occurring in the microenvironment of amino acids. To understand the robustness of the HSA-LOB complex, we used theoretical approaches, including molecular docking and MD simulations, and analyzed the principal component analysis and free energy landscape. These comprehensive studies of the structural features of biomolecules in ligand binding are of paramount importance for designing targeted drugs and delivery systems.
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Dicroismo Circular , Interacciones Hidrofóbicas e Hidrofílicas , Lobelina , Unión Proteica , Albúmina Sérica Humana , Termodinámica , Humanos , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Lobelina/química , Lobelina/metabolismo , Sitios de Unión , Dicroismo Circular/métodos , Conformación Proteica , Espectrometría de Fluorescencia , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/químicaRESUMEN
Block copolymers, composed of poly(2-oxazoline)s and poly(2-oxazine)s, can serve as drug delivery systems; they form micelles that carry poorly water-soluble drugs. Many recent studies have investigated the effects of structural changes of the polymer and the hydrophobic cargo on drug loading. In this work, we combine these data to establish an extended formulation database. Different molecular properties and fingerprints are tested for their applicability to serve as formulation-specific mixture descriptors. A variety of classification and regression models are built for different descriptor subsets and thresholds of loading efficiency and loading capacity, with the best models achieving overall good statistics for both cross- and external validation (balanced accuracies of 0.8). Subsequently, important features are dissected for interpretation, and the DrugBank is screened for potential therapeutic use cases where these polymers could be used to develop novel formulations of hydrophobic drugs. The most promising models are provided as an open-source software tool for other researchers to test the applicability of these delivery systems for potential new drug candidates.
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Sistemas de Liberación de Medicamentos , Interacciones Hidrofóbicas e Hidrofílicas , Aprendizaje Automático , Micelas , Polímeros , Polímeros/química , Sistemas de Liberación de Medicamentos/métodos , Oxazoles/química , Portadores de Fármacos/química , Oxazinas/química , Solubilidad , Química Farmacéutica/métodosRESUMEN
Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid-liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug-polymer interactions, are tested against the onset points of the CXB liquid-liquid phase separation (LLPS). It was found that the types of drug-polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB-polymer-water ternary phase diagram was drawn from the findings.