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1.
Nano Lett ; 24(11): 3432-3440, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38391135

ABSTRACT

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.


Subject(s)
Hyperuricemia , Peroxidase , Humans , Peroxidase/therapeutic use , Urate Oxidase/therapeutic use , Povidone/therapeutic use , Hyperuricemia/drug therapy , Hydrogen Peroxide , Uric Acid/metabolism , Oxidoreductases , Coloring Agents
2.
Anal Chem ; 96(39): 15797-15807, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39285721

ABSTRACT

Clustered regularly interspaced short palindromic repeats (CRISPR) technology has opened a new path for molecular diagnostics based on RNA programmed trans-cleavage activity. However, their accessibility for highly sensitive clinical diagnostics remains insufficient. In this study, we systematically investigated the impact of various surfactants on the CRISPR-Cas12a system and found that poly(vinylpyrrolidone) (PVP), a nonionic surfactant, showed the highest enhancement effect among these tested surfactants. Additionally, the enhancement effects of PVP are compatible and versatile to CRISPR-Cas12b and Cas13a systems, improving the sensitivity of these CRISPR-Cas systems toward synthetic targets by 1-2 orders of magnitude. By integrating the PVP-enhanced CRISPR system with isothermal nucleic acid amplification, both the two- and one-step assays exhibited comparable sensitivity and specificity to gold-standard quantitative polymerase chain reaction (qPCR) in the assay of clinical human papillomavirus (HPV) samples, thereby holding significant promise for advancing clinical diagnostics and biomedical research.


Subject(s)
CRISPR-Cas Systems , Povidone , CRISPR-Cas Systems/genetics , Povidone/chemistry , Humans , Nucleic Acid Amplification Techniques/methods , Surface-Active Agents/chemistry , Papillomaviridae/genetics
3.
Bioconjug Chem ; 35(4): 499-516, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38546823

ABSTRACT

Nanodroplet formation is important to achieve supersaturation of active pharmaceutical ingredients (APIs) in an amorphous solid dispersion. The aim of the current study was to explore how polymer composition, architecture, molar mass, and surfactant concentration affect polymer-drug nanodroplet morphology with the breast cancer API, GDC-0810. The impact of nanodroplet size and morphology on dissolution efficacy and drug loading capacity was explored using polarized light microscopy, dynamic light scattering, and cryogenic transmission electron microscopy. Poly(N-isopropylacrylamide-stat-N,N-dimethylacrylamide) (PND) was synthesized as two linear derivatives and two bottlebrush derivatives with carboxylated or PEGylated end-groups. Hydroxypropyl methylcellulose acetate succinate grade MF (HPMCAS-MF) and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) were included as commercial polymer controls. We report the first copolymerization synthesis of a PVPVA bottlebrush copolymer, which was the highest performing excipient in this study, maintaining 688 µg/mL GDC-0810 concentration at 60 wt % drug loading. This is likely due to strong polymer-drug noncovalent interactions and the compaction of GDC-0810 along the PVPVA bottlebrush backbone. Overall, it was observed that the most effective formulations had a hydrodynamic radius less than 25 nm with tightly compacted nanodroplet morphologies.


Subject(s)
Cinnamates , Indazoles , Polymers , Povidone/analogs & derivatives , Solubility
4.
Anal Biochem ; 694: 115604, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38986795

ABSTRACT

The extraction of high-quality RNA from cotton (Gossypium spp.) is challenging because of the presence of high polyphenolics, polysaccharides, quinones, and other secondary metabolites. A high-throughput RNA extraction protocol is a prerequisite. This Triton-X-100-based RNA extraction method utilizes Polyvinyl pyrrolidone polymer (PVPP) treatment which efficiently removes phenolics, and the application of Lithium chloride (LiCl) has been found that successfully precipitated the high-quality RNA from cotton tissue. Cytoplasmic male sterility (CMS) is a maternally inherited trait associated with specific mitochondrial genome rearrangements or mutations. The suitability of RNA extracted from Cotton CMS lines was assessed. cDNA was synthesized from RNA and assayed for mitochondrial genes (cox3, nad3, nad9) associated with male sterility. This paper discuss the advantages and limitation of this protocol over existing protocol for RNA extraction for polyphenolics-rich plant tissue.


Subject(s)
Gossypium , Polyphenols , RNA, Plant , Polyphenols/isolation & purification , Polyphenols/chemistry , RNA, Plant/isolation & purification , Gossypium/chemistry , Gossypium/genetics , Povidone/chemistry
5.
Biopolymers ; 115(5): e23606, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38888357

ABSTRACT

This study aimed to address a significant challenge in the application of bacterial cellulose (BC) within tissue engineering and regenerative medicine by tackling its inherent insolubility in water and organic solvents. Our team introduced a groundbreaking approach by utilizing zinc sulfate (ZnSO4) as a solvent to render BC soluble, a novel contribution to the literature. Subsequently, the obtained soluble BC was combined with varying concentrations of polyvinylpyrrolidone (PVP). Notably, we pioneered the fabrication of BC/PVP composite scaffolds with customizable fiber surface morphology and regulated degradation rates through the electrospun technique. Several key parameters, such as PVP concentration (8%, 15%, 12%, and 20% w/v), applied voltage (22, 15, and 12 kV), and a fixed nozzle-collector distance of 10 cm with a flow rate of 0.9 mL/h, were systematically evaluated so as to find the optimum parameter created BC/PVP product with electrospun. For electrospun BC/PVP products, a voltage of 12 kV was found to be optimal. Intriguingly, our findings revealed enhanced cell adhesion and proliferation in BC/PVP electrospun products compared with using PVP membranes alone. Specifically, cell viability for PVP and PVP/BC electrospun products was determined as 50.73% and 79.95%, respectively. In terms of thermal properties, the BC/PVP electrospun product exhibited a mass loss of 82.6% at 380°C, while PVP alone experienced 90.2% mass loss at around 280°C. Furthermore, the protein adhesion capacities were measured at 62.3 ± 1.2 µg for PVP and 99.4 ± 2 µg for BC/PVP electrospun products, whereas product showed no biodegradation over 28 days and had notable water retention capacity. In conclusion, our research not only successfully attained nanofiber morphology but also showcased enhanced cell attachment and proliferation on the BC/PVP electrospun product.


Subject(s)
Cellulose , Nanofibers , Povidone , Cellulose/chemistry , Nanofibers/chemistry , Povidone/chemistry , Tissue Engineering/methods , Cell Proliferation/drug effects , Cell Adhesion , Cell Survival/drug effects , Animals , Tissue Scaffolds/chemistry , Mice
6.
Biomed Microdevices ; 26(1): 9, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38189892

ABSTRACT

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.


Subject(s)
Lidocaine , Polymers , Humans , Anesthesia, Local , Polyvinyl Alcohol , Povidone
7.
Mol Pharm ; 21(2): 770-780, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38181202

ABSTRACT

The R3m molecular descriptor (R-GETAWAY third-order autocorrelation index weighted by the atomic mass) has previously been shown to encode molecular attributes that appear to be physically and chemically relevant to grouping diverse active pharmaceutical ingredients (API) according to their potential to form persistent amorphous solid dispersions (ASDs) with polyvinylpyrrolidone-vinyl acetate copolymer (PVPVA). The initial R3m dispersibility model was built by using a single three-dimensional (3D) conformation for each drug molecule. Since molecules in the amorphous state will adopt a distribution of conformations, molecular dynamics simulations were performed to sample conformations that are probable in the amorphous form, which resulted in a distribution of R3m values for each API. Although different conformations displayed R3m values that differed by as much as 0.4, the median of each R3m distribution and the value predicted from the single 3D conformation were very similar for most structures studied. The variability in R3m resulting from the distribution of conformations was incorporated into a logistic regression model for the prediction of ASD formation in PVPVA, which resulted in a refinement of the classification boundary relative to the model that only incorporated a single conformation of each API.


Subject(s)
Polymers , Povidone , Polymers/chemistry , Povidone/chemistry , Vinyl Compounds/chemistry , Drug Liberation , Solubility , Drug Compounding/methods
8.
Mol Pharm ; 21(7): 3591-3602, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38818946

ABSTRACT

Coamorphous and cocrystal drug delivery systems provide attractive crystal engineering strategies for improving the solubilities, dissolution rates, and oral bioavailabilities of poorly water-soluble drugs. Polymeric additives have often been used to inhibit the unwanted crystallization of amorphous drugs. However, the transformation of a coamorphous phase to a cocrystal phase in the presence of polymers has not been fully elucidated. Herein, we investigated the effects of low concentrations of the polymeric excipients poly(ethylene oxide) (PEO) and poly(vinylpyrrolidone) (PVP) on the growth of carbamazepine-celecoxib (CBZ-CEL) cocrystals from the corresponding coamorphous phase. PEO accelerated the growth rate of the cocrystals by increasing the molecular mobility of the coamorphous system, while PVP had the opposite effect. The coamorphous CBZ-CEL system exhibited two anomalously fast crystal growth modes: glass-to-crystal (GC) growth in the bulk and accelerated crystal growth at the free surface. These two fast growth modes both disappeared after doping with PEO (1-3% w/w) but were retained in the presence of PVP, indicating a potential correlation between the two fast crystal growth modes. We propose that the different effects of PEO and PVP on the crystal growth modes arose from weaker effects of the polymers on cocrystallization at the surface than in the bulk. This work provides a deep understanding of the mechanisms by which polymers influence the cocrystallization kinetics of a multicomponent amorphous phase and highlights the importance of polymer selection in stabilizing coamorphous systems or preparing cocrystals via solid-based methods.


Subject(s)
Carbamazepine , Crystallization , Polyethylene Glycols , Polymers , Povidone , Solubility , Polymers/chemistry , Polyethylene Glycols/chemistry , Carbamazepine/chemistry , Povidone/chemistry , Excipients/chemistry , Glass/chemistry
9.
Mol Pharm ; 21(8): 3967-3978, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39018110

ABSTRACT

The metastability of amorphous formulations poses barriers to their safe and widespread commercialization. The propensity of amorphous solid dispersions (ASDs) to crystallize is directly linked to their molecular structure. Amorphous structures are inherently complex and thus difficult to fully characterize by experiments, which makes structural simulations an attractive route for investigating which structural characteristics correlate with ASD stability. In this study, we use empirical potential structure refinement (EPSR) to create molecular models of ketoprofen-poly(vinylpyrrolidone) (KTP/PVP) ASDs with 0-75 wt % drug loading. The EPSR technique uses X-ray total scattering measurements as constraints, yielding models that are consistent with the X-ray data. We perform several simulations to assess the sensitivity of the EPSR approach to input parameters such as intramolecular bond rotations, PVP molecule length, and PVP tacticity. Even at low drug loading (25 wt %), ∼40% of KTP molecules participate in KTP-KTP hydrogen bonding. The extent of KTP-PVP hydrogen bonding does not decrease significantly at higher drug loadings. However, the models' relative uncertainties are too large to conclude whether ASDs' lower stabilities at high drug loadings are due to changes in drug-excipient hydrogen bonding or a decrease in steric hindrance of KTP molecules. This study illustrates how EPSR, combined with total scattering measurements, can be a powerful tool for investigating structural characteristics in amorphous formulations and developing ASDs with improved stability.


Subject(s)
Ketoprofen , Povidone , X-Ray Diffraction , Ketoprofen/chemistry , Povidone/chemistry , X-Ray Diffraction/methods , Crystallization , Chemistry, Pharmaceutical/methods , Drug Compounding/methods , Models, Molecular , Drug Stability
10.
Mol Pharm ; 21(6): 3027-3039, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38755753

ABSTRACT

This study presents a novel approach by utilizing poly(vinylpyrrolidone)s (PVPs) with various topologies as potential matrices for the liquid crystalline (LC) active pharmaceutical ingredient itraconazole (ITZ). We examined amorphous solid dispersions (ASDs) composed of ITZ and (i) self-synthesized linear PVP, (ii) self-synthesized star-shaped PVP, and (iii) commercial linear PVP K30. Differential scanning calorimetry, X-ray diffraction, and broad-band dielectric spectroscopy were employed to get a comprehensive insight into the thermal and structural properties, as well as global and local molecular dynamics of ITZ-PVP systems. The primary objective was to assess the influence of PVPs' topology and the composition of ASD on the LC ordering, changes in the temperature of transitions between mesophases, the rate of their restoration, and finally the solubility of ITZ in the prepared ASDs. Our research clearly showed that regardless of the PVP type, both LC transitions, from smectic (Sm) to nematic (N) and from N to isotropic (I) phases, are effectively suppressed. Moreover, a significant difference in the miscibility of different PVPs with the investigated API was found. This phenomenon also affected the solubility of API, which was the greatest, up to 100 µg/mL in the case of starPVP 85:15 w/w mixture in comparison to neat crystalline API (5 µg/mL). Obtained data emphasize the crucial role of the polymer's topology in designing new pharmaceutical formulations.


Subject(s)
Calorimetry, Differential Scanning , Itraconazole , Liquid Crystals , Povidone , Solubility , X-Ray Diffraction , Itraconazole/chemistry , Liquid Crystals/chemistry , Povidone/chemistry , Calorimetry, Differential Scanning/methods , X-Ray Diffraction/methods , Polymers/chemistry , Antifungal Agents/chemistry , Drug Compounding/methods , Crystallization , Chemistry, Pharmaceutical/methods
11.
Mol Pharm ; 21(6): 3017-3026, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38758116

ABSTRACT

Sucrose and trehalose pharmaceutical excipients are employed to stabilize protein therapeutics in a dried state. The mechanism of therapeutic protein stabilization is dependent on the sugars being present in an amorphous solid-state. Colyophilization of sugars with high glass transition polymers, polyvinylpyrrolidone (PVP), and poly(vinylpyrrolidone vinyl acetate) (PVPVA), enhances amorphous sugar stability. This study investigates the stability of colyophilized sugar-polymer systems in the frozen solution state, dried state postlyophilization, and upon exposure to elevated humidity. Binary systems of sucrose or trehalose with PVP or PVPVA were lyophilized with sugar/polymer ratios ranging from 2:8 to 8:2. Frozen sugar-PVPVA solutions exhibited a higher glass transition temperature of the maximally freeze-concentrated amorphous phase (Tg') compared to sugar-PVP solutions, despite the glass transition temperature (Tg) of PVPVA being lower than PVP. Tg values of all colyophilized systems were in a similar temperature range irrespective of polymer type. Greater hydrogen bonding between sugars and PVP and the lower hygroscopicity of PVPVA influenced polymer antiplasticization effects and the plasticization effects of residual water. Plasticization due to water sorption was investigated in a dynamic vapor sorption humidity ramping experiment. Lyophilized sucrose systems exhibited increased amorphous stability compared to trehalose upon exposure to the humidity. Recrystallization of trehalose was observed and stabilized by polymer addition. Lower concentrations of PVP inhibited trehalose recrystallization compared to PVPVA. These stabilizing effects were attributed to the increased hydrogen bonding between trehalose and PVP compared to trehalose and PVPVA. Overall, the study demonstrated how differences in polymer hygroscopicity and hydrogen bonding with sugars influence the stability of colyophilized amorphous dispersions. These insights into excipient solid-state stability are relevant to the development of stabilized biopharmaceutical solid-state formulations.


Subject(s)
Drug Stability , Excipients , Freeze Drying , Polymers , Povidone , Transition Temperature , Trehalose , Freeze Drying/methods , Povidone/chemistry , Trehalose/chemistry , Excipients/chemistry , Polymers/chemistry , Sucrose/chemistry , Sugars/chemistry , Hydrogen Bonding , Drug Storage , Chemistry, Pharmaceutical/methods , Calorimetry, Differential Scanning , Humidity , Pyrrolidines/chemistry , Vinyl Compounds/chemistry
12.
Mol Pharm ; 21(8): 4074-4081, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39008633

ABSTRACT

Amorphous solid dispersions (ASDs) can be used to enhance the solubility and bioavailability of poorly soluble drugs. An ASD is often a ternary system containing a drug, a surfactant, and a polymer. Recent work on binary ASDs has observed significant differences between surface and bulk compositions, with impacts on wettability and stability. Here we investigate a ternary ASD composed of the antifungal posaconazole, the surfactant Span 80, and a dispersion polymer (PVP or PVP/VA). The surfactant loading was fixed at the typical level of 5 wt %, and the drug/polymer ratio was varied. We observed strong surface enrichment of the surfactant and simultaneous depletion of the drug. This effect is already pronounced in the binary drug-surfactant system and is enhanced by the addition of the polymers. Between the two polymers, the more hydrophilic PVP causes a stronger enhancement of the surface enrichment effect. These results demonstrate the impact of component interactions on the surface composition of ASDs and the performance.


Subject(s)
Hydrophobic and Hydrophilic Interactions , Polymers , Solubility , Surface-Active Agents , Surface-Active Agents/chemistry , Polymers/chemistry , Wettability , Triazoles/chemistry , Antifungal Agents/chemistry , Povidone/chemistry , Hexoses
13.
Mol Pharm ; 21(10): 5104-5114, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39259772

ABSTRACT

Dissolving microneedle (DMN)-assisted transdermal drug delivery (TDD) has received attention from the scientific community in recent years due to its ability to control the rate of drug delivery through its design, the choice of polymers, and its composition. The dissolution of the polymer depends strongly on the polymer-solvent interaction and polymer physics. Here, we developed a mathematical model based on the physicochemical parameters of DMNs and polymer physics to determine the drug release profiles. An annular gap width is defined when the MN is inserted in the skin, accumulating interstitial fluid (ISF) from the surrounding skin and acting as a boundary layer between the skin and the MN. Poly(vinylpyrrolidone) (PVP) is used as a model dissolving polymer, and ceftriaxone is used as a representative drug. The model agrees well with the literature data for ex vivo permeation studies, along with the percent height reduction of the MN. Based on the suggested mathematical model, when loading 0.39 mg of ceftriaxone, the prediction indicates that approximately 93% of the drug will be cleared from the bloodstream within 24 h. The proposed modeling strategy can be utilized to optimize drug transport behavior using DMNs.


Subject(s)
Administration, Cutaneous , Drug Delivery Systems , Needles , Polymers , Drug Delivery Systems/methods , Polymers/chemistry , Skin Absorption/drug effects , Skin/metabolism , Models, Theoretical , Ceftriaxone/administration & dosage , Ceftriaxone/pharmacokinetics , Povidone/chemistry , Drug Liberation , Animals , Solubility
14.
Langmuir ; 40(27): 14007-14015, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38916446

ABSTRACT

Allograft transplantation is an important method for tendon reconstruction after injury, and its clinical success highly relies on the storage and transportation of the grafts. Cryopreservation is a promising strategy for tendon storage. In this study, we report a novel cryopreservation agent (CPA) formulation with a high biocompatibility for tendon cryopreservation. Mainly composed of natural zwitterionic betaine and the biocompatible polymer poly(vinylpyrrolidone) (PVP), it exhibited ideal abilities to depress the freezing point and inhibit ice growth and recrystallization. Notably, after cryopreservation via plunge-freezing for 1 month, Young's modulus (144 MPa, 98% of fresh tendons) and ultimate stress (46.7 MPa, 99% of fresh tendons) remained stable, and the cross-linking of collagen microfibers, protein structures, and glycosaminoglycan (GAG) contents changed slightly. These results indicate that the formulation (5 wt % betaine and 5 wt % PVP in phosphate-buffered saline, PBS solution) effectively maintains the biomechanical properties and tissue structure. This work offers a novel cryopreservation method for tendons and may also provide insights into the long-term preservation of various other tissues.


Subject(s)
Betaine , Cryopreservation , Tendons , Cryopreservation/methods , Tendons/drug effects , Betaine/chemistry , Animals , Freezing , Cryoprotective Agents/chemistry , Cryoprotective Agents/pharmacology , Povidone/chemistry , Collagen/chemistry , Glycosaminoglycans/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
15.
Langmuir ; 40(20): 10589-10599, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38728854

ABSTRACT

Optically transparent glass with antifogging and antibacterial properties is in high demand for endoscopes, goggles, and medical display equipment. However, many of the previously reported coatings have limitations in terms of long-term antifogging and efficient antibacterial properties, environmental friendliness, and versatility. In this study, inspired by catfish and sphagnum moss, a novel photoelectronic synergy antifogging and antibacterial coating was prepared by cross-linking polyethylenimine-modified titanium dioxide (PEI-TiO2), polyvinylpyrrolidone (PVP), and poly(acrylic acid) (PAA). The as-prepared coating could remain fog-free under hot steam for more than 40 min. The experimental results indicate that the long-term antifogging properties are due to the water absorption and spreading characteristics. Moreover, the organic-inorganic hybrid of PEI and TiO2 was first applied to enhance the antibacterial performance. The Staphylococcus aureus and the Escherichia coli growth inhibition rates of the as-prepared coating reached 97 and 96% respectively. A photoelectronic synergy antifogging and antibacterial mechanism based on the positive electrical and photocatalytic properties of PEI-TiO2 was proposed. This investigation provides insight into designing multifunctional bioinspired surface materials to realize antifogging and antibacterial that can be applied to medicine and daily lives.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Staphylococcus aureus , Titanium , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Titanium/chemistry , Titanium/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacology , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Microbial Sensitivity Tests , Povidone/chemistry , Surface Properties
16.
Pharm Res ; 41(7): 1521-1531, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38955998

ABSTRACT

PURPOSE: Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations. METHODS: The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations. RESULTS: The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute-solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively. CONCLUSION: PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed.


Subject(s)
Cimetidine , Molecular Dynamics Simulation , Povidone , Solubility , Cimetidine/chemistry , Povidone/chemistry , Polyethylene Glycols/chemistry , Polymers/chemistry , Crystallization , Excipients/chemistry , Spectrum Analysis, Raman , Thermodynamics , Kinetics , Water/chemistry
17.
Pharm Res ; 41(6): 1233-1245, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744732

ABSTRACT

PURPOSE: This study was designed to develop ibuprofen (IBU) sustained-release amorphous solid dispersion (ASD) using polymer composites matrix with drug release plateaus for stable release and to further reveal intrinsic links between polymer' matrix ratios and drug release behaviors. METHODS: Hydrophilic polymers and hydrophobic polymers were combined to form different composite matrices in developing IBU ASD formulations by hot melt extrusion technique. The intrinsic links between the mixed polymer matrix ratio and drug dissolution behaviors was deeply clarified from the dissolution curves of hydrophilic polymers and swelling curves of composite matrices, and intermolecular forces among the components in ASDs. RESULTS: IBU + ammonio methacrylate copolymer type B (RSPO) + poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP VA64) physical mixtures presented unstable release behaviors with large error bars due to inhomogeneities at the micrometer level. However, IBU-RSPO-PVP VA64 ASDs showed a "dissolution plateau phenomenon", i.e., release behaviors of IBU in ASDs were unaffected by polymer ratios when PVP VA64 content was 35% ~ 50%, which could reduce risks of variations in release behaviors due to fluctuations in prescriptions/processes. The release of IBU in ASDs was simultaneously regulated by the PVP VA64-mediated "dissolution" and RSPO-PVP VA64 assembly-mediated "swelling". Radial distribution function suggested that similar intermolecular forces between RSPO and PVP VA64 were key mechanisms for the "dissolution plateau phenomenon" in ASDs at 35% ~ 50% of PVP VA64. CONCLUSIONS: This study provided ideas for developing ASD sustained-release formulations with stable release plateau modulated by polymer combinations, taking full advantages of simple process/prescription, ease of scale-up and favorable release behavior of ASD formulations.


Subject(s)
Delayed-Action Preparations , Drug Compounding , Drug Liberation , Ibuprofen , Polymers , Delayed-Action Preparations/chemistry , Ibuprofen/chemistry , Ibuprofen/administration & dosage , Polymers/chemistry , Drug Compounding/methods , Hydrophobic and Hydrophilic Interactions , Solubility , Hot Melt Extrusion Technology/methods , Vinyl Compounds/chemistry , Pyrrolidines/chemistry , Chemistry, Pharmaceutical/methods , Povidone/chemistry
18.
Analyst ; 149(11): 3078-3084, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38717228

ABSTRACT

This study is the first to identify bovine blastocysts through in vitro fertilization (IVF) of matured oocytes with a large quantity of high-quality sperm separated from a biomimetic cervix environment. We obtained high-quality sperm in large quantities using an IVF sperm sorting chip (SSC), which could mimic the viscous environment of the bovine cervix during ovulation and facilitates isolation of progressively motile sperm from semen. The viscous environment-on-a-chip was realized by formulating and implementing polyvinylpyrrolidone (PVP)-based solutions for the SSC medium. Sperm separated from the IVF-SSC containing PVP 1.5% showed high motility, normal morphology and high DNA integrity. As a result of IVF, a higher rate of hatching blastocysts, which is the pre-implantation stage, were observed, compared to the conventional swim-up method. Our results may significantly contribute to improving livestock with superior male and female genetic traits, thus overcoming the limitation of artificial insemination based on the superior genetic traits of existing males.


Subject(s)
Embryonic Development , Fertilization in Vitro , Spermatozoa , Animals , Cattle , Male , Spermatozoa/cytology , Spermatozoa/chemistry , Female , Fertilization in Vitro/methods , Embryonic Development/physiology , Biomimetics/methods , Cervix Uteri/cytology , Povidone/chemistry , Blastocyst/cytology , Sperm Motility/drug effects
19.
Phys Chem Chem Phys ; 26(35): 22941-22958, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39171443

ABSTRACT

Excessive use of food coloring agents in the food industry to make the food more attractive or improve the taste has caused various health and ecological problems. Therefore, it is necessary to develop a reliable, sensitive, and selective sensing probe to detect food dyes in different food products for future industrial processing and biosafety. In recent decades, surface-functionalized quantum dots (QDs), owing to their unique optical properties, have gained tremendous interest for a wide range of applications, including biomedical, bioimaging and sensing applications. Herein, we have reported the synthesis of excellent colloidal stable and highly luminescent CdTe core and CdTe@ZnTe core-shell QDs using dual functionalizing agents, polyvinyl pyrrolidone and vitamin C. The synthesized QDs were explored as excellent sensing probes for the food dyes carmoisine, Ponceau 4R and tartrazine with limit of detection (LOD) values of 0.097 ± 0.006, 0.147 ± 0.001 and 0.044 ± 0.001 µM for CdTe-PVP QDs and 0.079 ± 0.001, 0.114 ± 0.002 and 0.042 ± 0.001 µM for CdTe@ZnTe-PVP QDs, respectively. The sensitivity of the synthesized QDs for the food dyes was also investigated in real samples (soft drinks and medications). Moreover, considering the potential effects of QDs as therapeutics or nano-drug carriers, the interactions between the synthesized QDs and carrier protein human serum albumin (HSA) were investigated. The binding affinity was observed to be in the order of 104 M-1. QDs were found to quench the intrinsic fluorescence of HSA, and both types of quenching (static and dynamic) occur via electrostatic interactions in association with hydrophobic forces without any significant alteration in the protein structure.


Subject(s)
Cadmium Compounds , Quantum Dots , Tellurium , Quantum Dots/chemistry , Tellurium/chemistry , Cadmium Compounds/chemistry , Humans , Food Coloring Agents/analysis , Food Coloring Agents/chemistry , Protein Binding , Zinc/chemistry , Ascorbic Acid/chemistry , Limit of Detection , Serum Albumin, Human/chemistry , Serum Albumin, Human/analysis , Povidone/chemistry
20.
Environ Res ; 252(Pt 3): 119068, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38705452

ABSTRACT

Cellulose acetate membranes exhibit a potential to be applied in hemodialysis. However, their performance is limited by membrane fouling and a lack of antibacterial properties. In this research, copper oxide (I) nanoparticles were fabricated in situ into a cellulose acetate matrix in the presence of polyvinylpyrrolidone (pore-forming agent) and sulfobetaine (stabilising agent) to reduce the leakage of copper ions from nano-enhanced membranes. The influence of nanoparticles on the membrane structure and their antibacterial and antifouling properties were investigated. The results showed that incorporating Cu2O NPs imparted significant antibacterial properties against Staphylococcus aureus and fouling resistance under physiological conditions. The Cu2O NPs-modified membrane could pave the way for potential dialysis applications.


Subject(s)
Anti-Bacterial Agents , Biofouling , Cellulose , Copper , Membranes, Artificial , Staphylococcus aureus , Cellulose/analogs & derivatives , Cellulose/chemistry , Cellulose/pharmacology , Copper/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Biofouling/prevention & control , Nanoparticles/chemistry , Metal Nanoparticles/chemistry , Povidone/chemistry , Povidone/analogs & derivatives
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