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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly... (Review)
Review
Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.
Topics: Biological Availability; Humans; Solubility; Emulsions; Lipids; Chemical Precipitation; Pharmaceutical Preparations; Chemistry, Pharmaceutical; Drug Compounding; Polymers; Drug Delivery Systems; Excipients; Animals
PubMed: 38815207
DOI: 10.2478/acph-2024-0023 -
World Journal of Gastrointestinal... May 2024Constipation is a significant sociomedical problem, which can be caused by various reasons. In the diagnostic approach to patients with constipation, the following data...
Constipation is a significant sociomedical problem, which can be caused by various reasons. In the diagnostic approach to patients with constipation, the following data are usually sufficient: History, complete physical examination (including rectal examination), and additional diagnostic tests. A colonoscopy is not a necessary diagnostic method for all patients with constipation. However, if patients have alarm symptoms/signs, that suggest an organic reason for constipation, a colonoscopy is necessary. The most important alarm symptoms/signs are age > 50 years, gastrointestinal bleeding, new-onset constipation, a palpable mass in the abdomen and rectum, weight loss, anemia, inflammatory bowel disease, and family history positive for colorectal cancer. Most endoscopists do not like to deal with patients with constipation. There are two reasons for this, namely the difficulty of endoscopy and the adequacy of preparation. Both are adversely affected by constipation. To improve the quality of colonoscopy in these patients, good examination techniques and often more extensive preparation are necessary. Good colonoscopy technique implies adequate psychological preparation of the patient, careful insertion of the endoscope with minimal insufflation, and early detection and resolution of loops. Bowel preparation for colonoscopy often requires prolonged preparation and sometimes the addition of other laxatives.
PubMed: 38813573
DOI: 10.4253/wjge.v16.i5.244 -
Heliyon May 2024The effects of vaccination are modified by hematological and autoimmune diseases and/or treatment. Anti-SARS-CoV-2 mRNA vaccine contains polyethylene glycol (PEG), it is...
Humoral immune response against SARS-CoV-2 and polyethylene glycol elicited by anti-SARS-CoV-2 mRNA vaccine, and effect of pre-existing anti-polyethylene glycol antibody in patients with hematological and autoimmune diseases.
BACKGROUND
The effects of vaccination are modified by hematological and autoimmune diseases and/or treatment. Anti-SARS-CoV-2 mRNA vaccine contains polyethylene glycol (PEG), it is largely unknown whether PEG influences the effects of vaccination or induces a humoral response. This study examined whether anti-PEG antibodies before vaccination (pre-existing) influenced the acquisition of SARS-CoV-2 antibodies and evaluated the relationship between the development of anti-SARS-CoV-2 antibodies and anti-PEG antibodies after SARS-CoV-2 vaccination in hematological and autoimmune diseases.
METHODS
Anti-SARS-CoV-2 antibody IgG, anti-PEG IgG, and IgM titers were evaluated in patients with hematological and autoimmune diseases after the second dose of BNT162B2. Anti-PEG IgG and IgM titers were also measured before vaccination to examine changes after vaccination and the relationship with vaccine efficacy.
RESULTS
In patients with hematological (n = 182) and autoimmune diseases (n = 96), anti-SARS-CoV-2 and anti-PEG antibody titers were evaluated after a median of 33 days from 2nd vaccination. The median anti-SARS-CoV-2 antibody titers were 1901 AU/mL and 3832 AU/mL in patients with hematological and autoimmune disease, respectively. Multiple regression analysis showed that age and days from 2nd vaccination were negatively associated with anti-SARS-CoV-2 antibody titers. Anti-CD20 antibody treatment was negatively correlated with anti-SARS-CoV-2 antibody titers in hematological disease, and C-reactive protein (CRP) was positively correlated with anti-SARS-CoV-2 antibody titers in autoimmune disease. Baseline anti-PEG antibody titers were significantly higher in patients with autoimmune disease but were not correlated with anti-SARS-CoV-2 antibody titers. Patients with increased anti-PEG IgG acquired higher anti-SARS-CoV-2 antibody titers in patients with autoimmune disease.
CONCLUSIONS
Anti-SARS-CoV-2 antibody acquisition was suboptimal in patients with hematological disease, but both anti-SARS-CoV-2 antibody and anti-PEG IgG were acquired in patients with autoimmune disease, reflecting robust humoral immune response. Pre-existing anti-PEG antibody titers did not affect anti-SARS-CoV-2 antibody acquisition.
PubMed: 38813140
DOI: 10.1016/j.heliyon.2024.e31489 -
RSC Advances May 2024Traditionally, waterborne polyurethanes (WPUs) are prepared using toxic organic solvents and catalysts. These WPUs are non-biodegradable and are buried or incinerated...
Traditionally, waterborne polyurethanes (WPUs) are prepared using toxic organic solvents and catalysts. These WPUs are non-biodegradable and are buried or incinerated after the expiration date. This has adverse effects on the environment and human health, which limits the applications of WPUs. Herein, a special synthetic method was developed for biodegradable waterborne polyurethane (BWPU) by adding hydrophilic prepolymers into WPU prepolymers without using organic solvents and catalysts. Different proportions of polyethylene glycol (PEG) were introduced into polycaprolactone (PCL)-based BWPUs to improve the comprehensive properties. Results showed that as the PEG content was increased from 0 to 16 wt%, the solid content of BWPU increased from 34.8 wt% to 53.1 wt%, while the tensile strength and Young's modulus of BWPU films increased from 21.81 MPa to 56.83 MPa and 8.08 MPa to 19.4 MPa, respectively. However, the elongation at break did not decrease significantly, but still reached 827.17%. With an increase in PEG content, the crystallinity and phase separation decreased, while the hydrophilicity and surface energy increased for BWPU films. In addition, the prepared BWPUs had good biodegradability in PBS/lipase solution. The mass loss of BWPU without PEG reached 6.3 wt% after 4 weeks of degradation, whereas the mass losses of BWPUs with PEG reached 2.3-4.3 wt%. Obviously, the introduction of PEG did not increase biodegradability. Thus, the higher the PCL content, the faster the biodegradation rate. This work would provide an effective method for the preparation of ecofriendly biodegradable BWPU with excellent comprehensive properties.
PubMed: 38813130
DOI: 10.1039/d4ra02044h -
RSC Advances May 2024The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted...
The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted end-group modifications on a variety of biodegradable polyesters, including poly(1,4-butylene adipate) (PBA), poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(-dioxanone) (PPDO), based on the precursor polyethylene glycol (PEG). By combining two polymers through the Biginelli multi-component reaction, four new biodegradable polyester copolymers, namely DHPM-PBA, DHPM-PCL, DHPM-PLA, and DHPM-PPDO, were formed. These Biginelli reactions demonstrated exceptional completeness, validating the efficiency of the synthesis strategy. Although the introduction of various polyesters lead to different properties, such as crystallinity and cytotoxicity, the newly synthesized 3,4-dihydro-2()-pyrimidinone compounds (DHPMs) exhibit enhanced hydrophilicity and can self-assemble in water and ,-dimethylformamide (DMF) solution to form micelles with a controllable size. Furthermore, DHPM-PPDO promotes cellular growth and has potential applications in wound healing and tissue engineering. In conclusion, this method demonstrates great universality and methodological significance and offers insights into the medical applications of polyethylene glycol.
PubMed: 38813120
DOI: 10.1039/d4ra02002b -
Frontiers in Bioscience (Landmark... May 2024Oliver is a unique high-quality natural rubber tree species and rare medicinal tree species in China. The rapid characterization of gene function has been severely...
BACKGROUND
Oliver is a unique high-quality natural rubber tree species and rare medicinal tree species in China. The rapid characterization of gene function has been severely hampered by the limitations of genetic transformation methods and breeding cycles. The polyethylene glycol (PEG)-mediated protoplast transformation system is a multifunctional and rapid tool for the analysis of functional genes , but it has not been established in .
METHODS
In this study, a large number of highly active protoplasts were isolated from the stems of seedlings by enzymatic digestion, and green fluorescent protein expression was facilitated using a PEG-mediated method.
RESULTS
Optimal enzymatic digestion occurred when the enzyme was digested for 10 h in an enzymatic solution containing 2.5% Cellulase R-10 (w/v), 0.6% Macerozyme R-10 (w/v), 2.5% pectinase (w/v), 0.5% hemicellulase (w/v), and 0.6 mol/L mannitol. The active protoplast yield under this condition was 1.13 × 106 protoplasts/g fresh weight, and the protoplast activity was as high as 94.84%.
CONCLUSIONS
This study established the first protoplasm isolation and transient transformation system in hard rubber wood, which lays the foundation for subsequent functional studies of genes to achieve high-throughput analysis, and provides a reference for future gene function studies of medicinal and woody plants.
Topics: Protoplasts; Eucommiaceae; Transfection; Green Fluorescent Proteins; Polyethylene Glycols
PubMed: 38812327
DOI: 10.31083/j.fbl2905187 -
BMC Surgery May 2024Whether polyetheretherketone (PEEK) rods have potential as an alternative to titanium alloy (Ti) rods in transforaminal lumbar interbody fusion (TLIF) remains unclear,... (Comparative Study)
Comparative Study
BACKGROUND
Whether polyetheretherketone (PEEK) rods have potential as an alternative to titanium alloy (Ti) rods in transforaminal lumbar interbody fusion (TLIF) remains unclear, especially in cases with insufficient anterior support due to the absence of a cage. The purpose of this study was to investigate biomechanical differences between PEEK rods and Ti rods in TLIF with and without a cage.
METHODS
An intact L1-L5 lumbar finite element model was constructed and validated. Accordingly, four TLIF models were developed: (1) Ti rods with a cage; (2) PEEK rods with a cage; (3) Ti rods without a cage; and (4) PEEK rods without a cage. The biomechanical properties were then compared among the four TLIF constructs.
RESULTS
With or without a cage, no obvious differences were found in the effect of PEEK rods and Ti rods on the range of motion, adjacent disc stress, and adjacent facet joint force. Compared to Ti rods, PEEK rods increase the average bone graft strain (270.8-6055.2 µE vs. 319.0-8751.6 µE). Moreover, PEEK rods reduced the stresses on the screw-rod system (23.1-96.0 MPa vs. 7.2-48.4 MPa) but increased the stresses on the cage (4.6-35.2 MPa vs. 5.6-40.9 MPa) and endplates (5.7-32.5 MPa vs. 6.6-37.6 MPa).
CONCLUSIONS
Regardless of whether a cage was used for TLIF, PEEK rods theoretically have the potential to serve as an alternative to Ti rods because they may provide certain stability, increase the bone graft strain, and reduce the posterior instrumentation stress, which might promote bony fusion and decrease instrumentation failure.
Topics: Benzophenones; Titanium; Ketones; Polymers; Finite Element Analysis; Polyethylene Glycols; Humans; Spinal Fusion; Biomechanical Phenomena; Lumbar Vertebrae; Alloys; Range of Motion, Articular; Biocompatible Materials
PubMed: 38811965
DOI: 10.1186/s12893-024-02462-8 -
International Journal of Nanomedicine 2024Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are...
PURPOSE
Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are prompting an urgent search for more effective therapeutic tools. Consequently, to increase the treatment efficiency and to reduce the side effects of traditional administration ways, herein, it has become crucial to combine photodynamic therapy as a promising therapeutic approach with the selectivity and biocompatibility of a novel colloidal transdermal nanoplatform for effective delivery of hybrid cargo with synergistic effects on melanoma cells.
METHODS
The self-assembled bilosomes, co-stabilized with L-α-phosphatidylcholine, sodium cholate, Pluronic P123, and cholesterol, were designated, and the stability of colloidal vesicles was studied using dynamic and electrophoretic light scattering, also provided in cell culture medium (Dulbecco's Modified Eagle's Medium). The hybrid compounds - a classical photosensitizer (Methylene Blue) along with a complementary natural polyphenolic agent (curcumin), were successfully co-loaded, as confirmed by UV-Vis, ATR-FTIR, and fluorescent spectroscopies. The biocompatibility and usefulness of the polymer functionalized bilosome with loaded double cargo were demonstrated in vitro cyto- and phototoxicity experiments using normal keratinocytes and melanoma cancer cells.
RESULTS
The in vitro bioimaging and immunofluorescence study upon human skin epithelial (A375) and malignant (Me45) melanoma cell lines established the protective effect of the PEGylated bilosome surface. This effect was confirmed in cytotoxicity experiments, also determined on human cutaneous (HaCaT) keratinocytes. The flow cytometry experiments indicated the enhanced uptake of the encapsulated hybrid cargo compared to the non-loaded MB and CUR molecules, as well as a selectivity of the obtained nanocarriers upon tumor cell lines. The phyto-photodynamic action provided 24h-post irradiation revealed a more significant influence of the nanoplatform on Me45 cells in contrast to the A375 cell line, causing the cell viability rate below 20% of the control.
CONCLUSION
As a result, we established an innovative and effective strategy for potential metastatic melanoma treatment through the synergism of phyto-photodynamic therapy and novel bilosomal-origin nanophotosensitizers.
Topics: Humans; Skin Neoplasms; Melanoma; Photochemotherapy; Cell Line, Tumor; Photosensitizing Agents; Curcumin; Nanomedicine; Cell Survival; Liposomes; Cholesterol; Phosphatidylcholines; Sodium Cholate; Drug Delivery Systems; Poloxalene
PubMed: 38808148
DOI: 10.2147/IJN.S450181 -
Plant Cell Reports May 2024Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide,...
Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide, hydrogen sulfide, and antioxidant systems for enhanced drought tolerance. While nitric oxide (NO), a signalling molecule, enhances plant tolerance to abiotic stresses, its precise contribution to improving tomato tolerance to drought stress (DS) through modulating oxide-nitrosative processes is not yet fully understood. We aimed to examine the interaction of NO and nitrosative signaling, revealing how sodium nitroprusside (SNP) could mitigate the effects of DS on tomatoes. DS-seedlings endured 12% polyethylene glycol (PEG) in a 10% nutrient solution (NS) for 2 days, then transitioned to half-strength NS for 10 days alongside control plants. DS reduced total plant dry weight, chlorophyll a and b, Fv/Fm, leaf water potential (Ψ), and relative water content, but improved hydrogen peroxide (HO), proline, and NO content. The SNP reduced the DS-induced HO generation by reducing thiol (-SH) and the carbonyl (-CO) groups. SNP increased not only NO but also the activity of L-cysteine desulfhydrase (L-DES), leading to the generation of HS. Decreases in S-nitrosoglutathione reductase (GSNOR) and NADPH oxidase (NOX) suggest a potential regulatory mechanism in which -nitrosylation [formation of S-nitrosothiol (SNO)] may influence protein function and signaling pathways during DS. Moreover, SNP improved ascorbate (AsA) and glutathione (GSH) and reduced oxidized glutathione (GSSG) levels in tomato plants under drought. Furthermore, the interaction of NO and HS, mediated by L-DES activity, may serve as a vital cross-talk mechanism impacting plant responses to DS. Understanding these signaling interactions is crucial for developing innovative drought-tolerance strategies in crops.
Topics: Nitroprusside; Solanum lycopersicum; Hydrogen Peroxide; Droughts; Nitric Oxide; Glutathione; Antioxidants; Oxidation-Reduction; Oxidative Stress; Stress, Physiological; Seedlings; Plant Leaves; Nitrosation; Chlorophyll
PubMed: 38806834
DOI: 10.1007/s00299-024-03238-3 -
Scientific Reports May 2024Polyetheretherketone (PEEK) is considered as an excellent biomaterial for bone grafting and connective tissue replacement. The clinical potential is, however, limited by...
Polyetheretherketone (PEEK) is considered as an excellent biomaterial for bone grafting and connective tissue replacement. The clinical potential is, however, limited by its bioinertness, poor osteoconduction, and weak antibacterial activity. These disadvantages can be overcome by introducing suitable additives to produce mineral-polymer composites or coatings. In this work, a PEEK-based bioactive composite has been obtained by blending the polymer with magnesium phosphate (Mg(PO)) particles in amounts ranging from 1 to 10 wt.% using the hot press technique. The obtained composite exhibited improved mechanical and physical properties, above the lower limits set for bone engineering applications. The tested grafts were found to not induce cytotoxicity. The presence of magnesium phosphate induced the mineralisation process with no adverse effects on the expression of the marker crucial for osteoblastic differentiation. The most promising results were observed in the grafts containing 1 wt.% of magnesium phosphate embedded within the PEEK matrix. The improved bioactivity of grafts, together with suitable physical-chemical and mechanical properties, indicate this composite as a promising orthopaedic implant material.
Topics: Benzophenones; Ketones; Polymers; Polyethylene Glycols; Biocompatible Materials; Phosphates; Humans; Magnesium Compounds; Materials Testing; Osteoblasts
PubMed: 38806564
DOI: 10.1038/s41598-024-61941-3