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1.
PLoS One ; 19(6): e0303900, 2024.
Article in English | MEDLINE | ID: mdl-38843120

ABSTRACT

BACKGROUND: Candesartan cilexetil (CC) is a selective angiotensin II receptor antagonist widely used to treat hypertension. CC is a substrate of P-glycoprotein (P-gp), causing its efflux to the intestinal lumen. It is also practically insoluble in water and has low oral bioavailability (14%). Thus, the current study aims to improve the in vitro dissolution of CC by developing solid dispersion systems (SDSs) and corroborating the in vitro results using a simulated pharmacokinetics study. METHODS: The SDSs were prepared using polyvinyl pyrrolidone (PVP) as a water-soluble polymer, Eudragit E100 (EE100) as a pH-dependent soluble carrier, and a combination of these two polymers. The saturation solubility and the dissolution rate studies of the prepared systems in three dissolution media were performed. The optimized system SE-EE5 was selected for further investigations, including DSC, XRD, FTIR, FESEM, DLS, TSEM, IVIVC convolution study, and stability studies. RESULTS: The solubility of CC significantly increased by a factor of 27,037.344 when formulated as a solid dispersion matrix using EE100 at a ratio of 1:5 (w/w) drug to polymer (SE-EE5 SD), compared to the solubility of the pure drug. The mechanism of solubility and dissolution rate enhancement of CC by the optimized SDS was found to be via the conversion of the crystalline CC into the amorphous form as well as nanoparticles formation upon dissolution at a pH below 5. The instrumental analysis tests showed good compatibility between CC and EE100 and there was no chemical interaction between the drug and the polymer. Moreover, the stability tests confirmed that the optimized system was stable after three months of storage at 25°C. CONCLUSION: The utilization of the solid dispersion technique employing EE 100 polymer as a matrix demonstrates significant success in enhancing the solubility, dissolution, and subsequently, the bioavailability of water-insoluble drugs like CC.


Subject(s)
Benzimidazoles , Biphenyl Compounds , Polymers , Solubility , Tetrazoles , Benzimidazoles/chemistry , Benzimidazoles/pharmacokinetics , Tetrazoles/chemistry , Tetrazoles/pharmacokinetics , Biphenyl Compounds/chemistry , Biphenyl Compounds/pharmacokinetics , Polymers/chemistry , Polymers/pharmacokinetics , Povidone/chemistry , Water/chemistry , Hydrogen-Ion Concentration , Biological Availability , Drug Stability , Drug Liberation , Acrylates
2.
J Nanobiotechnology ; 22(1): 217, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725012

ABSTRACT

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.


Subject(s)
Antioxidants , Bandages , Chitosan , Hydrogels , Platelet-Rich Plasma , Povidone , Wound Healing , Chitosan/chemistry , Chitosan/analogs & derivatives , Chitosan/pharmacology , Wound Healing/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Povidone/chemistry , Povidone/analogs & derivatives , Hydrogels/chemistry , Hydrogels/pharmacology , Platelet-Rich Plasma/chemistry , Animals , Mice , Male , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Oxidative Stress/drug effects , Humans
3.
AAPS PharmSciTech ; 25(5): 103, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714634

ABSTRACT

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.


Subject(s)
Crystallization , Griseofulvin , Polymers , Transition Temperature , Griseofulvin/chemistry , Crystallization/methods , Polymers/chemistry , Drug Stability , Hydrogen Bonding , Polyvinyls/chemistry , Polyethylene Glycols/chemistry , Povidone/chemistry , Glass/chemistry
4.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791388

ABSTRACT

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C60 conjugate (FA-PVP-C60) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using 13C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C60 showed antiradical activity against •DPPH, •OH and O2•-, but at the same time, it was shown to generate 1O2. It was found that the conjugate in the studied concentration range (up to 200 µg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor.


Subject(s)
Drug Delivery Systems , Folic Acid , Fullerenes , Povidone , Folic Acid/chemistry , Folic Acid/pharmacology , Humans , Povidone/chemistry , Fullerenes/chemistry , Fullerenes/pharmacology , Drug Delivery Systems/methods , Cell Line, Tumor , A549 Cells , HeLa Cells , Particle Size
5.
Int J Pharm ; 658: 124204, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38710297

ABSTRACT

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.


Subject(s)
Antimalarials , Artesunate , Delayed-Action Preparations , Drug Liberation , Povidone , Printing, Three-Dimensional , Tablets , Artesunate/administration & dosage , Artesunate/chemistry , Artesunate/pharmacokinetics , Animals , Rabbits , Antimalarials/administration & dosage , Antimalarials/chemistry , Antimalarials/pharmacokinetics , Povidone/chemistry , Hypromellose Derivatives/chemistry , Excipients/chemistry , Drug Delivery Systems , Administration, Oral , Carboxymethylcellulose Sodium/chemistry , Poloxamer/chemistry , Gastric Mucosa/metabolism
6.
Eur J Pharm Sci ; 198: 106780, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38697312

ABSTRACT

Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.


Subject(s)
Drug Compounding , Drug Liberation , Solubility , Drug Compounding/methods , Povidone/chemistry , Computer Simulation , Pharmaceutical Preparations/chemistry , Least-Squares Analysis
7.
Anal Methods ; 16(19): 3007-3019, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38695537

ABSTRACT

We present a colorimetric probe based on polyvinylpyrrolidone-capped gold nanoparticles (PVP-AuNPs) that is sensitive and selective for cysteine (Cys). A microfluidic paper-based analytical device (µ-PAD) with embedded dried PVP-AuNPs at the polyethersulfone (PES) paper surface is used for Cys detection. When thiol molecules attach to PVP-AuNPs in the presence of Cys, they clump together, and this causes the solution's color to shift from red to blue within 5 minutes. The device is capable of detecting Cys levels between 1.0 µM and 50.0 µM with a limit of detection (LOD) of 0.2 µM under optimized conditions. The stability of the µ-PAD was tested for 100 days, demonstrating re-dispersibility to detect Cys levels in blood. Dried PVP-AuNP-µPADs were integrated with blood plasma separation modules for point-of-care (POC) Cys detection. Consequently, the device shows potential as a self-sustaining, quantification platform with a recovery percentage ranging from 98.44 to 111.9 in clinical samples.


Subject(s)
Colorimetry , Cysteine , Gold , Limit of Detection , Metal Nanoparticles , Paper , Point-of-Care Systems , Gold/chemistry , Cysteine/blood , Cysteine/chemistry , Metal Nanoparticles/chemistry , Humans , Colorimetry/methods , Colorimetry/instrumentation , Povidone/chemistry , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods
8.
Sci Rep ; 14(1): 10679, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724534

ABSTRACT

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.


Subject(s)
Aprepitant , Capsules , Particle Size , Povidone , Solvents , Capsules/chemistry , Povidone/chemistry , Solvents/chemistry , Aprepitant/chemistry , Solubility , Dimethylformamide/chemistry , Drug Liberation , Drug Compounding/methods , Temperature
9.
Int J Nanomedicine ; 19: 4339-4356, 2024.
Article in English | MEDLINE | ID: mdl-38774026

ABSTRACT

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.


Subject(s)
Curcumin , Doxorubicin , Povidone , Doxorubicin/chemistry , Doxorubicin/pharmacology , Doxorubicin/administration & dosage , Doxorubicin/pharmacokinetics , Povidone/chemistry , Curcumin/chemistry , Curcumin/pharmacology , Curcumin/pharmacokinetics , Cell Line, Tumor , Animals , Mice , Humans , Nanoparticles/chemistry , Particle Size , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Neoplasms/pathology , Photothermal Therapy/methods , Drug Liberation , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Drug Carriers/chemistry , Cell Survival/drug effects
10.
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
11.
Chem Biol Interact ; 396: 111064, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38768772

ABSTRACT

Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 µg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2ß: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.


Subject(s)
Administration, Intravenous , Povidone , Quercetin , Solubility , Water , Animals , Quercetin/pharmacokinetics , Quercetin/analogs & derivatives , Quercetin/administration & dosage , Quercetin/chemistry , Rats , Male , Water/chemistry , Povidone/chemistry , Benzalkonium Compounds/pharmacokinetics , Benzalkonium Compounds/chemistry , Rats, Wistar
12.
Int J Pharm ; 657: 124177, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38697582

ABSTRACT

We present a promising method for producing amorphous drug particles using a nozzle-free ultrasonic nebulizer with polymers, specifically polyvinylpyrrolidone (PVP), poly(acrylic acid) (PAA), and Eudragit® S 100 (EUD). Model crystalline phase drugs-Empagliflozin, Furosemide, and Ilaprazole-are selected. This technique efficiently produces spherical polymer-drug composite particles and demonstrates enhanced stability against humidity and thermal conditions, compared to the drug-only amorphous particles. The composite particles exhibit improved water dissolution compared to the original crystalline drugs, indicating potential bioavailability enhancements. While there are challenges, including the need for continuous water supply for ultrasonic component cooling, dependency on the solubility of polymers and drugs in volatile organic solvents, and mildly elevated temperatures for solvent evaporation, our method offers significant advantages over traditional approaches. It provides a straightforward, flexible process adaptable to various drug-polymer combinations and consistently yields spherical amorphous solid dispersion (ASD) particles with a narrow size distribution. These attributes make our method a valuable advancement in pharmaceutical drug formulation and delivery.


Subject(s)
Nebulizers and Vaporizers , Particle Size , Polymers , Polymers/chemistry , Drug Stability , Solubility , Drug Compounding/methods , Acrylic Resins/chemistry , Povidone/chemistry , Ultrasonics , Polymethacrylic Acids/chemistry , Furosemide/chemistry , Chemistry, Pharmaceutical/methods
13.
Int J Pharm ; 657: 124190, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38701910

ABSTRACT

Lubricants are essential for most tablet formulations as they assist powder flow, prevent adhesion to tableting tools and facilitate tablet ejection. Magnesium stearate (MgSt) is an effective lubricant but may compromise tablet strength and disintegratability. In the design of orodispersible tablets, tablet strength and disintegratability are critical attributes of the dosage form. Hence, this study aimed to conduct an in-depth comparative study of MgSt with alternative lubricants, namely sodium lauryl sulphate (SLS), stearic acid (SA) and hydrogenated castor oil (HCO), for their effects on the tableting process as well as tablet properties. Powder blends were prepared with lactose, sodium starch glycolate or crospovidone as the disintegrant, and a lubricant at different concentrations. Angle of repose was determined for the mixtures. Comparative evaluation was carried out based on the ejection force, tensile strength, liquid penetration and disintegratability of the tablets produced. As the lubricant concentration increased, powder flow and tablet ejection improved. The lubrication efficiency generally decreased as follows: MgSt > HCO > SA > SLS. Despite its superior lubrication efficacy, MgSt is the only lubricant of four evaluated that reduced tablet tensile strength. Tablet disintegration time was strongly determined by tensile strength and liquid penetration, which were in turn affected by the lubricant type and concentration. All the above factors should be taken into consideration when deciding the type and concentration of lubricant for an orodispersible tablet formulation.


Subject(s)
Excipients , Lubricants , Stearic Acids , Tablets , Tensile Strength , Lubricants/chemistry , Stearic Acids/chemistry , Excipients/chemistry , Drug Compounding/methods , Powders/chemistry , Sodium Dodecyl Sulfate/chemistry , Castor Oil/chemistry , Povidone/chemistry , Starch/chemistry , Starch/analogs & derivatives , Lactose/chemistry , Administration, Oral , Solubility , Chemistry, Pharmaceutical/methods
14.
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
15.
Molecules ; 29(10)2024 May 12.
Article in English | MEDLINE | ID: mdl-38792144

ABSTRACT

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 µM, 5 µM, and 10 µM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP's potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.


Subject(s)
Curcumin , Nanoparticles , Curcumin/pharmacology , Curcumin/chemistry , Animals , Rats , Nanoparticles/chemistry , Mice , Humans , Drug Delivery Systems , Nerve Regeneration/drug effects , Polymers/chemistry , Schwann Cells/drug effects , Drug Liberation , Tannins/chemistry , Tannins/pharmacology , Cell Line , Oxidative Stress/drug effects , Povidone/chemistry
16.
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
17.
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
18.
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
19.
Sci Total Environ ; 935: 173428, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38777065

ABSTRACT

The water-soluble polymer polyvinylpyrrolidone (PVP) is an established ingredient in pharmaceutical and personal care product (PPCP) formulations. Due to its high usage and lack of biodegradability, it has been detected up to 7.0 mg L-1 in wastewater and 0.1 mg L-1 in the receiving freshwaters, with several studies showing detrimental sublethal effects in a range of aquatic species. A lack of simple analytical methods to detect and quantify PVP currently impacts further investigation into the cause of these sublethal effects. In this paper we propose a refractive index gel-permeation chromatography (GPC) method to quantify PVP, which includes the processing of raw chromatograms using line deconvolution to calculate peak area. The method was then applied to Daphnia magna exposed to PVP for 48 h. A limit of detection (LOD) and limit of quantification (LOQ) of 0.05 and 0.2 mg mL-1 respectively was determined, with a recovery of 78 % from spiked Daphnia magna. PVP was detected in the samples above the LOD but below the LOQ. This suggests PVP is ingested by Daphnia magna, which warrants further investigation into whether bioaccumulation of PVP could be causing the sublethal effects seen in other studies.


Subject(s)
Daphnia , Povidone , Water Pollutants, Chemical , Animals , Daphnia/physiology , Daphnia/drug effects , Povidone/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Refractometry , Environmental Monitoring/methods , Aquatic Organisms/drug effects , Limit of Detection , Polymers , Daphnia magna
20.
Int J Biol Macromol ; 270(Pt 2): 132161, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723810

ABSTRACT

A novel magnetic polyvinylpyrrolidone/chitosan-Schiff base/Fe2O3 (PVP/CS-SB/Fe2O3) adsorbent was prepared by one-pot facile co-precipitation route for adsorption of Pb(II) and Hg(II) ions from aqueous solution. Fourier transform infrared-spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), vibrating sample magnetometer (VSM) and Brunauer-Emmett-Teller (BET) were used to characterize the synthesized PVP/CS-SB/Fe2O3. The results predicted that the successfully synthesis of magnetic CSSB-PVP@Fe2O3. The effects of important factors such as pH solution, contact time, concentration of metal ions, adsorbent dose and co-existing ions on Pb(II) and Hg(II) adsorption were investigated. The maximum adsorption capacities of Pb(II) and Hg(II) ions at optimal conditions were 120 mg/g and 102.5 mg/g, respectively. The kinetic studies predicted that the adsorption followed the pseudo-second-order (PSO) model as chemisorption using the coordination of active sites of PVP/CS-SB/Fe2O3 with the metal ions and also n-π interactions. Reproducibility results predicted that the excellent regeneration ability after 6 adsorption cycles. According to the results of this work, the PVP/CS-SB/Fe2O3 nanocomposite is promising for Pb(II) and Hg(II) ions adsorption and can be potential as a simple, low-cost, high-efficient adsorbent for decontamination of other heavy metal ions from aqueous solution.


Subject(s)
Chitosan , Ferric Compounds , Lead , Mercury , Nanocomposites , Povidone , Schiff Bases , Water Pollutants, Chemical , Water Purification , Chitosan/chemistry , Nanocomposites/chemistry , Adsorption , Schiff Bases/chemistry , Lead/chemistry , Lead/isolation & purification , Mercury/chemistry , Mercury/isolation & purification , Povidone/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Ferric Compounds/chemistry , Hydrogen-Ion Concentration , Water Purification/methods , Kinetics , Solutions , Ions/chemistry , Water/chemistry , Spectroscopy, Fourier Transform Infrared
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