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International Journal of Molecular... Jun 2024Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood...
Unfractionated heparin (UFH) and its low-molecular-weight fragments (LMWH) are widely used as anticoagulants for surgical procedures and extracorporeal blood purification therapies such as cardiovascular surgery and dialysis. The anticoagulant effect of heparin is essential for the optimal execution of extracorporeal blood circulation. However, at the end of these procedures, to avoid the risk of bleeding, it is necessary to neutralize it. Currently, the only antidote for heparin neutralization is protamine sulphate, a highly basic protein which constitutes a further source of serious side events and is ineffective in neutralizing LMWH. Furthermore, dialysis patients, due to the routine administration of heparin, often experience serious adverse effects, among which HIT (heparin-induced thrombocytopenia) is one of the most severe. For this reason, the finding of new heparin antagonists or alternative methods for heparin removal from blood is of great interest. Here, we describe the synthesis and characterization of a set of biocompatible macroporous cryogels based on poly(2-hydroxyethyl methacrylate) (pHEMA) and -lysine with strong filtering capability and remarkable neutralization performance with regard to UFH and LMWH. These properties could enable the design and creation of a filtering device to rapidly reverse heparin, protecting patients from the harmful consequences of the anticoagulant.
Topics: Heparin; Humans; Cryogels; Anticoagulants; Lysine; Heparin, Low-Molecular-Weight; Heparin Antagonists
PubMed: 38928208
DOI: 10.3390/ijms25126503 -
Biomolecules May 2024Hydrogels are three-dimensional crosslinked functional materials with water-absorbing and swelling properties. Many hydrogels can store a variety of small functional... (Review)
Review
Hydrogels are three-dimensional crosslinked functional materials with water-absorbing and swelling properties. Many hydrogels can store a variety of small functional molecules to structurally and functionally mimic the natural extracellular matrix; hence, they have been extensively studied for biomedical applications. Polyamidoamine (PAMAM) dendrimers have an ethylenediamine core and a large number of peripheral amino groups, which can be used to engineer various polymer hydrogels. In this review, an update on the progress of using PAMAM dendrimers for multifunctional hydrogel design was given. The synthesis of these hydrogels, which includes click chemistry reactions, aza-Michael addition, Schiff base reactions, amidation reactions, enzymatic reactions, and radical polymerization, together with research progress in terms of their application in the fields of drug delivery, tissue engineering, drug-free tumor therapy, and other related fields, was discussed in detail. Furthermore, the biomedical applications of PAMAM-engineered nano-hydrogels, which combine the advantages of dendrimers, hydrogels, and nanoparticles, were also summarized. This review will help researchers to design and develop more functional hydrogel materials based on PAMAM dendrimers.
Topics: Hydrogels; Dendrimers; Humans; Tissue Engineering; Polyamines; Drug Delivery Systems; Animals; Click Chemistry; Biocompatible Materials
PubMed: 38927024
DOI: 10.3390/biom14060620 -
Journal of Nanobiotechnology Jun 2024Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical... (Review)
Review
Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.
Topics: Humans; Animals; Gene Transfer Techniques; Genetic Therapy; Regeneration; Tissue Engineering; Tissue Scaffolds; Nanoparticles; Drug Carriers; Genetic Vectors
PubMed: 38926780
DOI: 10.1186/s12951-024-02580-8 -
Scientific Reports Jun 2024Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency....
Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-β-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-β cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs' antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (- 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.
Topics: Humans; Zein; Silybin; HT29 Cells; beta-Cyclodextrins; Antioxidants; Nanoparticles; Apoptosis; Cell Survival; Drug Carriers; Drug Delivery Systems; Antineoplastic Agents
PubMed: 38926533
DOI: 10.1038/s41598-024-65881-w -
Scientific Reports Jun 2024Long-chain polyunsaturated fatty acids (LCPUFA) are of interest due to their potential health properties and have a significant role in reducing the risk of various...
Long-chain polyunsaturated fatty acids (LCPUFA) are of interest due to their potential health properties and have a significant role in reducing the risk of various chronic diseases in humans. It is commonly used as a supplement. However, lipid oxidation is an important negative factor caused by environmental, processing, and limited water solubility of LCPUFA, making them difficult to incorporate into food products. The objective of this research work was to prevent oxidation, extend shelf life, enhance the stability of fatty acids, and to achieve controlled release by preparing spray-dried powder (SDM). For spray-drying, aqueous emulsion blends were formulated using a 1:1 ratio of chia seed oil (CSO) and fish oil (FO) and using a laboratory-scale spray-dryer with varying conditions: inlet air temperature (IAT, 125-185 °C), wall material (WM, 5-25%), pump speed (PS, 3-7 mL/min), and needle speed (NS, 3-11 s). The maximum alpha-linolenic acid (ALA) content was 33 ± 1%. The highest values of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the microcapsules were 8.4 ± 0.4 and 13 ± 1%, respectively. Fourier transform infrared and X-Ray diffraction analysis results indicated that SDM was successfully formulated with Gum Arabic and maltodextrin (MD). The blending without encapsulation of CSO and FO was digested more efficiently and resulted in more oil being released with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and SGF + SIF conditions without heating. No significant changes were observed for saturated, monounsaturated, and LCPUFA, whether exposed or not to gastrointestinal conditions. However, compared to the release of SDM, it can be useful for designing delivery systems for the controlled release of essential fatty acids.
Topics: Fish Oils; Capsules; Spray Drying; Plant Oils; Salvia; Fatty Acids; Humans
PubMed: 38926468
DOI: 10.1038/s41598-024-65214-x -
Scientific Reports Jun 2024The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract...
The aim of this study is to introduce a dental capping agent for the treatment of pulp inflammation (pulpitis). Nanohydroxyapatite with Elaeagnus angustifolia L. extract (nHAEA) loaded with metronidazole (nHAEA@MTZ) was synthesized and evaluated using a lipopolysaccharide (LPS) in vitro model of pulpitis. nHAEA was synthesized through sol-gel method and analyzed using Scanning Electron Microscopy, Transmission Electron Microscopy, and Brunauer Emmett Teller. Inflammation in human dental pulp stem cells (HDPSCs) induced by LPS. A scratch test assessed cell migration, RT PCR measured cytokines levels, and Alizarin red staining quantified odontogenesis. The nHAEA nanorods were 17-23 nm wide and 93-146 nm length, with an average pore diameter of 27/312 nm, and a surface area of 210.89 m/g. MTZ loading content with controlled release, suggesting suitability for therapeutic applications. nHAEA@MTZ did not affect the odontogenic abilities of HDPSCs more than nHAEA. However, it was observed that nHAEA@MTZ demonstrated a more pronounced anti-inflammatory effect. HDPSCs treated with nanoparticles exhibited improved migration compared to other groups. These findings demonstrated that nHAEA@MTZ could be an effective material for pulp capping and may be more effective than nHAEA in reducing inflammation and activating HDPSCs to enhance pulp repair after pulp damage.
Topics: Plant Extracts; Humans; Pulpitis; Metronidazole; Dental Pulp; Durapatite; Nanoparticles; Green Chemistry Technology; Drug Carriers; Stem Cells; Cell Movement; Cells, Cultured
PubMed: 38926433
DOI: 10.1038/s41598-024-65582-4 -
Biological & Pharmaceutical Bulletin 2024We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel...
We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.
Topics: Animals; Arginine; Hydrogels; Mice, Hairless; Skin Absorption; Administration, Cutaneous; Skin; Indomethacin; Decanoic Acids; Hydrocortisone; Mice; Rheology; Permeability; Male
PubMed: 38925923
DOI: 10.1248/bpb.b24-00078 -
Ceska a Slovenska Oftalmologie :... 2024The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to...
OBJECTIVE
The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment.
MATERIAL AND METHODS
This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated.
RESULTS
At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%).
CONCLUSION
Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).
Topics: Humans; Macular Edema; Male; Female; Diabetic Retinopathy; Dexamethasone; Retrospective Studies; Middle Aged; Aged; Intravitreal Injections; Drug Implants; Visual Acuity; Glucocorticoids; Tomography, Optical Coherence
PubMed: 38925895
DOI: 10.31348/2024/29 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Jun 2024The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising...
The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.
Topics: Tablets; Enalapril; Administration, Buccal; Mouth Mucosa; Drug Compounding; Chemistry, Pharmaceutical
PubMed: 38925868
DOI: 10.62958/j.cjap.2024.003 -
Anticancer Research Jul 2024This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal...
BACKGROUND/AIM
This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies.
PATIENTS AND METHODS
This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m body surface area, respectively. The primary outcome measures were feasibility and perioperative complications.
RESULTS
The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (T) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with T ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications.
CONCLUSION
In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.
Topics: Humans; Middle Aged; Female; Aged; Male; Peritoneal Neoplasms; Feasibility Studies; Retrospective Studies; Aerosols; Hyperthermia, Induced; Cisplatin; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Hyperthermic Intraperitoneal Chemotherapy; Oxaliplatin
PubMed: 38925817
DOI: 10.21873/anticanres.17117