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• There is a narrowing of the α -dispersion with pressure (p) in ritonavir (RTV). • The reason for that is most likely variation in the local molecular ordering with p. • Changes in H-bonding pattern are also responsible for the observed finding. • An additional secondary process emerges in the high- p spectra measured at T < T g. In this paper, high-pressure (HP) dielectric studies on H-bonded active pharmaceutical ingredient – ritonavir indicated the narrowing of α- dispersion with compression, and consequently, a breakdown of the temperature-pressure superpositioning rule. To understand such peculiar behavior, reported so far only for a few van der Waals compounds, we performed calorimetric, structural, and infrared measurements on the pressure densified glass (as well as on ordinary glass) of the examined substance. These investigations demonstrated that variations in the structural organization of molecules and H-bonding pattern are responsible for the observed changes in the shape of the structural relaxation peak. Moreover, further isobaric HP studies at pressure 400 MPa revealed the presence of an additional secondary relaxation process (not detected at p = 0.1 MPa) in the loss spectra collected below the glass transition temperature for this compound. [ABSTRACT FROM AUTHOR]

A series of anionic homopolymers, poly(sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and amphiphilic copolymers of AMPS and sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS75-b-PAaUn), and random (P(AMPSm-co-AaUn)), were synthesized and their antiviral activity against Zika virus (ZIKV) was evaluated. Interestingly, while the homopolymers showed limited antiviral activity, the copolymers are very efficient antivirals. This observation was explained considering that under the conditions relevant to the biological experiments (pH 7.4 PBS buffer) the macromolecules of these copolymers exist as negatively charged (zeta potential about −25 mV) nanoparticles (4–12 nm) due to their self-organization. They inhibit the ZIKV replication cycle by binding to the cell surface and thereby blocking virus attachment to host cells. Considering good solubility in aqueous media, low toxicity, and high selectivity index (SI) of the PAMPS-b-PAaU copolymers, they can be considered promising agents against ZIKV infections. [ABSTRACT FROM AUTHOR]

In this paper, we report 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) supported high-pressure approach enforcing Ring-Opening Polymerization (ROP) of γ-butyrolactone (GBL), that due to unfavorable thermodynamics and low ring strain, is considered as a hardly polymerizable monomer. Application of Broadband Dielectric Spectroscopy (BDS) allowed us to find optimal thermodynamic conditions to perform well-controlled and notably fast polymerization (even within 1 h!), avoiding undesired crystallization process. It was shown that by varying pressure and temperature conditions, we could control molecular weight, dispersity of recovered macromolecules, as well as rate and efficiency of the reaction that are significantly altered with respect to the reference process carried out at ambient conditions. Experiments performed at respectively very low temperature T = 233 K and low/moderate pressure (p = 75–250 MPa) and much higher temperatures (T = 248–268 K) and compressions (p = 1000 MPa) yielded poly(γ-butyrolactone) (PGBL) of tailored absolute molecular weight in moderate range M n = 2.8–15.0 (up to 30.3) kg/mol and narrow/moderate dispersity ranging from Đ = 1.12–1.89. What is more, the implementation of MALDI-TOF, GPC and DSC analyses, clearly indicated that as i) the time of reaction gets longer, ii) the amount of catalyst increases, iii) the temperature lowers, the content of cyclic products in produced polymers grows. This phenomenon influences the rheological properties (viscosity), foil formation ability (films) and cell culture proliferation features of the recovered macromolecules. Presented results open a highly effective and repeatable route to produce PGBL via pressure-assisted ROP and indicate the possibility of tuning properties of this polymer by varying concentration of cycles or eventual block copolymerization with other biorelevant monomers to meet the expectations of the biotechnological industry. [Display omitted] • Organocatalyzed high-pressure assisted γ-butyrolactone Ring-Opening Polymerization. • Well-defined macromolecules (M n up to 30.3 kg/mol; low to moderate Đ = 1.12–1.89). • External catalytic effect of high pressure: reduced reaction time; increased yield. • Monitoring the polymerization progress in situ using BDS technique. • Analysis: NMR, GPC, MALDI, DSC, SEM, rheology, cytotoxicity, cell proliferation. [ABSTRACT FROM AUTHOR]

• There is an anomalous narrowing of the α -peak with compression in acTRE and silTRE. • The temperature-pressure superpositioning is not satisfied in these systems. • The reason for that is probably a change in local structure of molecules at high p. • α-relaxation in silTRE is characterized by extremely high sensitivity to compression. In this paper, broadband dielectric spectroscopy (BDS) was applied to study the molecular dynamics of the methyl, acetyl, and silyl derivatives of trehalose, TRE (metTRE, acTRE, and silTRE, respectively) at high pressure (p). Unexpectedly, our investigations indicated a breakdown of the temperature–pressure superpositioning (TPS) in acTRE and silTRE since the α -loss peak got narrower during compression. Importantly, a similar finding has been reported earlier only for one low-molecular weight compound, i.e., tris(dimethylsiloxy)phenylsilane. Additional X-ray diffraction (XRD) measurements carried out on the ordinary and pressure densified glasses of acTRE indicated that the changes in the width of the α -process in this saccharide (and probably silTRE) are rather due to variations in the supramolecular structure and enhanced local ordering occurring at high p. What is more, we also thoroughly characterized the structural dynamics of three TRE derivatives at different thermodynamic conditions. It was found that the sensitivity of the α -relaxation to compression, reflected in the pressure coefficient of the glass transition temperature (d T g /d p) and activation volume for the α -process, Δ V α (at T = T g), increases with increasing molecular weight (M w) of the modified carbohydrate. Interestingly, for silTRE both d T g /d p and Δ V α were extremely high, reaching the following values: 453 K/GPa and 1049 cm3/mol, respectively. Our data clearly revealed a link between the local structure of compressed van der Waals liquids and peculiar anomalous variations in the shape of the structural process upon densification. [ABSTRACT FROM AUTHOR]

Poly(1-vinyl-2-pyrrolidone) (Povidone, PVP) is one of the most interesting and versatile synthetic polymers utilised in the pharmaceutical and cosmetic industries. Its large-scale commercial production offers an assortment of products in a wide range of molecular weights but poorly-controlled (macro)structural parameters (i.e., dispersity, functionality) limiting the efficiency of PVP-based drug delivery systems (DDS). In this work, synthesised linear and star-shaped PVPs with a strictly defined structure and functionality were compared with the linear, commercially-supplied product and explored as potential vehicles for physical entrapment of metronidazole (MTZ). Here, a question is addressed how differences in their macromolecular properties affect the amorphisation of MTZ, drug encapsulation, the stability of drug-loaded micellar structures and their in vitro release from the carrier. The X-ray diffraction studies and calorimetric measurements revealed that MTZ crystallises in all investigated herein systems reducing the glass transition temperature of the binary mixture significantly. Transmission electron microscopy and dynamic light scattering analysis revealed that MTZ-loaded DDS are able to form ultrasmall regular nanocarriers with an increasing effect of regularity and sphericity from star-shaped DDS to linear-based ones. We founded that synthesised linear-based DDS is the most effective for MTZ entrapment (PVP:MTZ = 1:1 weight ratio) due to their smallest hydrodynamic radius d h = 14.7 nm, the highest stability of micellar structures −2.37 mV, and the highest values of loaded drug 76.5%. Moreover, all applied PVP-based DDS revealed an initial burst release effect of MTZ (pH = 7.4) reaching up to 60% of drug released within the first 5 h (the first-order release model fits). The marked efficiency of MTZ-loaded DDS of strictly defined structural parameters indicates the great importance of polymer preparation strategy in the targeted therapy. [Display omitted] • Metronidazole-polyvinylpyrrolidone (MTZ-PVP) drug delivery systems were obtained using polymers of various topology. • Commercial linear pvp has been compared with synthesised linear and star ones in terms of ability to form stable micelles and solubilize MTZ. • MTZ-loaded DDS are able to form ultrasmall regular nanocarriers with an increasing effect of regularity and sphericity from star-shaped DDS to linear-based ones. • MTZ crystallises in all investigated herein systems reducing the glass transition temperature of the binary mixture significantly. • Synthesised linear-based DDS is the most effective for MTZ entrapment. [ABSTRACT FROM AUTHOR]

In this work, broadband dielectric spectroscopy (BDS) has been applied to investigate the aging kinetics in a low-molecular weight pharmaceutical - probucol (PRO) at various pressure (p) conditions. Unexpectedly, we found that isostructural relaxation times (τ i so , i.e., τ α in the glass), as well as the stretch exponent (β ag) calculated using the Casalini and Roland (CR) approach at 115 and 160 MPa, vary from the respective τ i so and β ag determined at 0.1 MPa. These results were different in regard to the data reported earlier for polymethylmethacrylate (PMMA). Further Fourier transform infrared (FTIR) measurements on the glass recovered from high- p experiments (pressure densified glass, PDG) allowed us to certify that most likely the change in the specific intermolecular interactions, namely the formation of weak, rarely observed O H⋯S hydrogen bonds might be responsible for that. Moreover, taking into account the values of β ag (free parameter) obtained from the analysis of aging data using the CR approach, we estimated primitive relaxation times (τ 0) from the Coupling Model, which were close to experimental Johari-Goldstein (JG) β -relaxation times (τ JG-β). Findings reported herein may contribute to a better understanding of the aging phenomenon occurring in the pressurized H-bonded systems. Unlabelled Image • τ i so calculated using the CR model at elevated p vary from those obtained at 0.1 MPa. • The observed behavior is different than that reported for polymethylmethacrylate. • Weak O H∙∙S hydrogen bonds are formed in probucol at high compression. • Our results enable a better understanding of the aging process in pressurized systems. [ABSTRACT FROM AUTHOR]

In this article, we have addressed fundamental relationships between the chemical structure, intermolecular order, degree of the association and the dynamical properties, including the nature of dielectric response function, the variation of the glass transition temperature and the Kirkwood factor in three homologues phenyl derivatives of monohydroxy alcohols: 1-phenyl-2-butanol, 4-phenyl-1-butanol, and 4-phenyl-2-butanol. Dielectric data supported by infrared and diffraction investigations allowed us to certify that the Debye relaxation can be detected not only in aliphatic but also aromatic monohydroxy alcohols, suggesting its universal character, irrespectively of the chemical structure and steric hindrance. Moreover, we discovered that besides water, 4-phenyl-1-butanol is a next H-bonded system that exhibits the Debye-like relaxation process and no sign of the diffraction pre-peak being a fingerprint of the medium-range intermolecular order. This finding alters our understanding of the molecular origin of the scattering pre-peak and Debye-type process in diffractograms and dielectric loss spectra, respectively. Finally, we revealed that the activation volume, which is a measure of the volume required for reorientational motions of molecules to occur, is the greatest for the system with the highest Kirkwood factor at the glass transition temperature. It means that except the static parameters characterising the size of the supramolecular associates, their morphology, and the degree of intermolecular order, also dynamical quantity related to the volume of relaxing supramolecular structures is required to understand the fluctuations in the Kirkwood factor, and generally, the behaviour of associating liquids at varying thermodynamic conditions. • Phenyl alcohols forming strong hydrogen bonds. • Main contribution to dielectric loss peak in phenyl alcohols due to Debye relaxation. • Debye relaxation universal in aliphatic and aromatic monohydroxy alcohols. • Debye mode in associating, hydrogen-bonded liquids with no diffraction pre-peak. • Static and dynamic parameters determining the molecular dynamics. [ABSTRACT FROM AUTHOR]

In this paper, thermal and structural properties, as well as molecular dynamics of co-amorphous binary mixtures composed of itraconazole (ITZ) and four other active pharmaceutical ingredients (APIs) with antifungal activity (posaconazole (POS), ketoconazole (KET), fluconazole (FLU), and voriconazole (VOR)), have been investigated. Calorimetric measurements indicated that with increasing concentration of each excipient (EXC), the glass transition temperature and phase transition temperatures, related to the formation of nematic and smectic order, are affected in the binary systems. Comprehensive analysis of the enthalpy of isotropic-nematic transition and the temperature dependence of the order parameter, calculated from infrared data for selected mixtures, supported by the results of X-ray diffraction , enabled us to confirm the suppression of liquid crystalline (LC) ordering in ITZ by KET, FLU, and VOR. On the other hand, ITZ enforced the nematic-like molecular arrangement of POS. Further dielectric measurements revealed that the type of EXC and its content in the mixture have no impact on the ratio of α - and δ -relaxation times (τ α and τ δ , respectively) in ITZ. Moreover, it was shown that δ -process is more sensitive to the isotropic-nematic phase transition than the α -one, and the formation of the nematic phase in this API occurs at different τ α and τ δ , dependently on the type of EXC and its concentration in the mixture. Summarizing, the results of our studies are much different with respect to those reported previously by Kozyra et al. [Mol. Pharm. 15 (2018) 5192–5206] and by some of us [Kaminska et al. Eur. J. Pharm. Biopharm. 88 (2014) 1094–1104] for ITZ mixed with various polymers and acetylated maltose, respectively. This finding clearly indicates that there is a different impact of the low and high molecular weight excipients on the ability in the formation of LC phases in ITZ, which may have important implications for the further development of the formulations of this pharmaceutical. Unlabelled Image • The degree of spatial arrangement of ITZ molecules is affected in binary systems. • The smectic ordering in ITZ is being suppressed by POS, KET, FLU and VOR. • In the ITZ-POS binary mixture, ITZ enforces the molecular (nematic) order of POS. • Results of our studies are in contrast to those reported for ITZ-polymer systems. [ABSTRACT FROM AUTHOR]

Pioglitazone, a popular antidiabetic drug, which was recently shown to be effective in the treatment of skin ulcers, was successfully encapsulated in polysaccharide nanoparticles and used as a bioactive component of the wound-dressing material based on modified bacterial nanocellulose. Alginate and hydroxypropyl cellulose were used as a matrix for the nanoparticulate drug-delivery system. The matrix composition and particles' size, as well as drug encapsulation efficiency and loading, were optimized. Pioglitazone hydrochloride (PIO) loaded particles were coated with chitosan introduced into the crosslinking medium, and covalently attached to the surface of bacterial nanocellulose functionalized with carboxyl groups. PIO was released from the surface of the hybrid material in a controlled manner for 5 days. Preliminary cytotoxicity studies confirmed safety of the system at PIO concentrations as high as 20 mg/mL. The obtained hybrid system may have potential application in the treatment of skin ulcers e.g., in diabetic foot. [ABSTRACT FROM AUTHOR]