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Polymers Jun 2024Six differently charged amphoteric polyamidoamines, synthesized by the polyaddition of ,'-methylenebisacrylamide to alanine, leucine, serine, arginine (M-ARG), glutamic...
Six differently charged amphoteric polyamidoamines, synthesized by the polyaddition of ,'-methylenebisacrylamide to alanine, leucine, serine, arginine (M-ARG), glutamic acid (M-GLU) and a glycine/cystine mixture, were screened for their short-term phytotoxicity using a seed germination test. L. seeds were incubated in polyamidoamine water solutions with concentrations ranging from 0.156 to 2.5 mg mL at 25 ± 1 °C for 120 h. The seed germination percentage (%), an indicator of acute toxicity, and both root and shoot elongation, related to plant maturation, were the considered endpoints. The germination index () was calculated as the product of relative seed germination times relative radical growth. The % values were in all cases comparable to those obtained in water, indicating no detectable acute phytotoxicity of the polyamidoamines. In the short term, the predominantly positively charged M-ARG proved to be phytotoxic at all concentrations ( < 0.8), whereas the predominantly negatively charged M-GLU proved to be biostimulating at intermediate concentrations ( > 1) and slightly inhibitory at 2.5 mg mL (0.8 < < 1). Overall, polyamidoamine phytotoxicity could be correlated to charge distribution, demonstrating the potential of the test for predicting and interpreting the eco-toxicological behavior of water-soluble polyelectrolytes.
PubMed: 38932092
DOI: 10.3390/polym16121744 -
Polymers Jun 2024In this study, we report an easy approach for the production of aqueous dispersions of C fullerene with good stability. Maleic acid copolymers, poly(styrene--maleic...
In this study, we report an easy approach for the production of aqueous dispersions of C fullerene with good stability. Maleic acid copolymers, poly(styrene--maleic acid) (SM), poly(N-vinyl-2-pyrrolidone--maleic acid) (VM) and poly(ethylene--maleic acid) (EM) were used to stabilize C fullerene molecules in an aqueous environment by forming non-covalent complexes. Polymer conjugates were prepared by mixing a solution of fullerene in N-methylpyrrolidone (NMP) with an aqueous solution of the copolymer, followed by exhaustive dialysis against water. The molar ratios of maleic acid residues in the copolymer and C were 5/1 for SM and VM and 10/1 for EM. The volume ratio of NMP and water used was 1:1.2-1.6. Water-soluble complexes (composites) dried lyophilically retained solubility in NMP and water but were practically insoluble in non-polar solvents. The optical and physical properties of the preparations were characterized by UV-Vis spectroscopy, FTIR, DLS, TGA and XPS. The average diameter of the composites in water was 120-200 nm, and the ξ-potential ranged from -16 to -20 mV. The bactericidal properties of the obtained nanostructures were studied. Toxic reagents and time-consuming procedures were not used in the preparation of water-soluble C nanocomposites stabilized by the proposed copolymers.
PubMed: 38932086
DOI: 10.3390/polym16121736 -
Polymers Jun 2024Chitosan/modified cassava starch/curcumin (CS/S/Cur) films with a crosslinker were developed via the solvent casting technique for the application of food packaging. The...
Chitosan/modified cassava starch/curcumin (CS/S/Cur) films with a crosslinker were developed via the solvent casting technique for the application of food packaging. The effects of citric acid (CA) as a natural crosslinker were assessed at different concentrations (0-10.0%, /, on a dry base on CS and S content). To measure the most favorable film, chemical structure and physical, mechanical, and thermal properties were investigated. Successful crosslinking between CS and S was seen clearly in the Fourier Transform Infrared (FTIR) spectra. The properties of the water resistance of the CS/S/Cur films crosslinked with CA were enhanced when compared to those without CA. Furthermore, it was found that the addition of CA crosslinking would improve the mechanical properties of composite films to some extent. It had been reported that the CA crosslinking level of 7.5 wt% of CS/S/Cur film demonstrated high performance in terms of physical properties. The tensile strength of the crosslinked film increased from 8 ± 1 MPa to 12 ± 1 MPa with the increasing content of CA, while water vapor permeability (WVP), swelling degree (SD), and water solubility (WS) decreased. An effective antioxidant scavenging activity of the CS/S/Cur film decreased with an increase in CA concentrations. This study provides an effective pathway for the development of active films based on polysaccharide-based film for food packaging applications.
PubMed: 38931996
DOI: 10.3390/polym16121647 -
Polymers Jun 2024Bovine serum albumin (BSA) hydrogels are non-immunogenic, low-cost, biocompatible, and biodegradable. In order to avoid toxic cross-linking agents, gellan was oxidized...
Bovine serum albumin (BSA) hydrogels are non-immunogenic, low-cost, biocompatible, and biodegradable. In order to avoid toxic cross-linking agents, gellan was oxidized with NaIO to obtain new functional groups like dialdehydes for protein-based hydrogel cross-linking. The formed dialdehyde groups were highlighted with FT-IR and NMR spectroscopy. This paper aims to investigate hydrogel films for biomedical applications obtained by cross-linking BSA with oxidized gellan (OxG) containing immobilized β-cyclodextrin-curcumin inclusion complex (β-CD-Curc) The β-CD-Curc improved the bioavailability and solubility of Curc and was prepared at a molar ratio of 2:1. The film's structure and morphology were evaluated using FT-IR spectroscopy and SEM. The swelling degree (Q%) values of hydrogel films depend on hydrophilicity and pH, with higher values at pH = 7.4. Additionally, the conversion index of -NH groups into Schiff bases increases with an increase in OxG amount. The polymeric matrix provides protection for Curc, is non-cytotoxic, and enhances antioxidant activity. At pH = 5.5, the skin permeability and release efficiency of encapsulated curcumin were higher than at pH = 7.4 because of the interaction of free aldehyde and carboxylic groups from hydrogels with amine groups from proteins present in the skin membrane, resulting in a better film adhesion and more efficient curcumin release.
PubMed: 38931981
DOI: 10.3390/polym16121631 -
Pharmaceutics Jun 2024Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this...
Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this study, novel pharmaceutical cocrystals of PROG were successfully prepared by solvent evaporation or a liquid-assisted grinding process aimed at enhancing its solubility and bioavailability. The cocrystal formers selected based on crystal engineering principles were carboxylic acids, namely, 4-formylbenzeneboronic acid (BBA), isophthalic acid (IPA), and 3-nitrophthalic acid (NPA). The cocrystal structures were characterized using multiple techniques. Single-crystal X-ray diffraction results showed that the carbonyl group, acting as a hydrogen bond acceptor, was pivotal in the cocrystal network formation, with C-H···O interactions further stabilizing the crystals. The cocrystals exhibited improved solubility and dissolution profiles in vitro, with no significant changes in hygroscopicity. The parallel artificial membrane permeability assay (PAMPA) models indicated that the cocrystals retained PROG's high permeability. Pharmacokinetic studies in Sprague-Dawley rats revealed that all cocrystals increased PROG exposure, with AUC values for PROG-BBA, PROG-IPA, and PROG-NPA being 742.59, 1201.72 and 442.67 h·ng·mL, respectively. These values are substantially higher compared to free PROG, which had an AUC of 301.48 h·ng·mL. Notably, PROG-IPA provided the highest AUC improvement, indicating a significant enhancement in bioavailability. Collectively, the study concludes that the cocrystal approach is a valuable strategy for optimizing the physicochemical properties and oral bioavailability of PROG, with potential implications for the development of other poor water-soluble drugs.
PubMed: 38931937
DOI: 10.3390/pharmaceutics16060816 -
Pharmaceutics Jun 2024In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the...
In this study, we present a new type of polymer-free hydrogel made only from nonionic surfactants, oil, and water. Such a system is produced by taking advantage of the physicochemical behavior and interactions between nonionic surfactants and oil and water phases, according to a process close to spontaneous emulsification used in the production of nano-emulsions. Contrary to the classical process of emulsion-based gel formulation, we propose a simple one-step approach. Beyond the originality of the concept, these appear as very promising systems able to encapsulate and deliver various molecules with different solubilities. In the first section, we propose a comprehensive investigation of the gel formation process and its limits through oscillatory rheological characterization, characterization of the sol/gel transitions, and gel strength. The second section is focused on the follow-up of the release of an encapsulated model hydrophilic molecule and on the impact of the rheological gel properties on the release profiles.
PubMed: 38931933
DOI: 10.3390/pharmaceutics16060812 -
Pharmaceutics Jun 2024Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal...
Influence of Mechanical Loading on the Process of Tribochemical Action on Physicochemical and Biopharmaceutical Properties of Substances, Using Lacosamide as an Example: From Micronisation to Mechanical Activation.
Many physical and chemical properties of solids, such as strength, plasticity, dispersibility, solubility and dissolution are determined by defects in the crystal structure. The aim of this work is to study in situ dynamic, dispersion, chemical, biological and surface properties of lacosamide powder after a complete cycle of mechanical loading by laser scattering, electron microscopy, FR-IR and biopharmaceutical approaches. The SLS method demonstrated the spontaneous tendency toward surface-energy reduction due to aggregation during micronisation. DLS analysis showed conformational changes of colloidal particles as supramolecular complexes depending on the loading time on the solid. SEM analysis demonstrated the conglomeration of needle-like lacosamide particles after 60 min of milling time and the transition to a glassy state with isotropy of properties by the end of the tribochemistry cycle. The following dynamic properties of lacosamide were established: elastic and plastic deformation boundaries, region of inhomogeneous deformation and fracture point. The ratio of dissolution-rate constants in water of samples before and after a full cycle of loading was 2.4. The lacosamide sample, which underwent a full cycle of mechanical loading, showed improved kinetics of API release via analysis of dissolution profiles in 0.1 M HCl medium. The observed activation-energy values of the cell-death biosensor process in aqueous solutions of the lacosamide samples before and after the complete tribochemical cycle were 207 kJmol and 145 kJmol, respectively. The equilibrium time of dissolution and activation of cell-biosensor death corresponding to 20 min of mechanical loading on a solid was determined. The current study may have important practical significance for the transformation and management of the properties of drug substances in solid form and in solutions and for increasing the strength of drug matrices by pre-strain hardening via structural rearrangements during mechanical loading.
PubMed: 38931919
DOI: 10.3390/pharmaceutics16060798 -
Pharmaceutics Jun 2024Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19...
UNLABELLED
Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to these symptoms, leading to a USD 50 billion annual loss of salary. Neurological symptoms associated with long COVID result from persistent infection with SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous system (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in olfactory mucosa. Recently published clinical data demonstrate that only 5% of long COVID anosmia patients have fully recovered during the past 2 years, and 10.4% of COVID patients are still symptomatic 18 months post-infection. Our group demonstrated that epigallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activity against human coronavirus, suggesting that this green-tea-derived compound in nanoparticle formulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to restoration of neurologic functions. The objective of the current study was to evaluate the mucociliary safety of the EC16m nasal nanoformulations and their efficacy against human coronavirus.
METHODS
Nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using the MucilAir human nasal model; contact antiviral activity and post-infection inhibition against the OC43 viral strain were assessed by the TCID50 assay for cytopathic effect on MRC-5 cells.
RESULTS
The saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% / EC16m have no significant difference compared to saline (0.9% NaCl) with respect to tissue integrity, cytotoxicity, and cilia beat frequency. A 5 min contact resulted in 99.9% inactivation of β-coronavirus OC43. OC43 viral replication was inhibited by >90% after infected MRC-5 cells were treated with the formulations.
CONCLUSION
The saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety properties comparable to saline, a solution widely used for nasal applications.
PubMed: 38931912
DOI: 10.3390/pharmaceutics16060791 -
Pharmaceutics Jun 2024Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug...
Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.
PubMed: 38931905
DOI: 10.3390/pharmaceutics16060784 -
Pharmaceutics Jun 2024Understanding the pharmacokinetics, safety and efficacy of candidate drugs is crucial for their success. One key aspect is the characterization of absorption,...
Understanding the pharmacokinetics, safety and efficacy of candidate drugs is crucial for their success. One key aspect is the characterization of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, which require early assessment in the drug discovery and development process. This study aims to present an innovative approach for predicting ADMET properties using attention-based graph neural networks (GNNs). The model utilizes a graph-based representation of molecules directly derived from Simplified Molecular Input Line Entry System (SMILE) notation. Information is processed sequentially, from substructures to the whole molecule, employing a bottom-up approach. The developed GNN is tested and compared with existing approaches using six benchmark datasets and by encompassing regression (lipophilicity and aqueous solubility) and classification (CYP2C9, CYP2C19, CYP2D6 and CYP3A4 inhibition) tasks. Results show the effectiveness of our model, which bypasses the computationally expensive retrieval and selection of molecular descriptors. This approach provides a valuable tool for high-throughput screening, facilitating early assessment of ADMET properties and enhancing the likelihood of drug success in the development pipeline.
PubMed: 38931898
DOI: 10.3390/pharmaceutics16060776