ABSTRACT
Standard zirconia implants used in restoration still present problems related to inertness and long-term stability. Various physicochemical approaches have been used to modify the implant surfaces to improve early and late bone-to-implant integration; however, no ideal surface modification has been reported. This study used pulsed laser deposition to deposit a fluorinated hydroxyapatite (FHA) film on a zirconia implant to create a biologically active surface. The film prepared was uniform, dense, and crack-free, and exhibited granular surface droplets; it also presented excellent mechanical strength and favorable biological behavior. The FHA-coated implant was implanted on the femur of Sprague-Dawley rats, and various tests and analyses were performed. Results show that the in vitro initial cell activity on the FHA-coated samples was enhanced. In addition, higher alkaline phosphatase activity and cell mineralization were detected in cells cultured on the FHA-coated groups. Further, the newly formed bone volume of the FHA-coated group was higher than that of the bare micro-adjusted composite nano-zirconia (NANOZR) group. Therefore, the FHA film facilitated osseointegration and may improve the long-term survival rates of dental implants, and could become part of a new treatment technology for implant surfaces, promoting further optimization of NANOZR implant materials.
Subject(s)
Coated Materials, Biocompatible/administration & dosage , Durapatite/chemistry , Femur/surgery , Fluorine/chemistry , Osseointegration/drug effects , Zirconium/administration & dosage , Alkaline Phosphatase/metabolism , Animals , Cells, Cultured , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Dental Implants , Femur/cytology , Femur/drug effects , Femur/metabolism , Lasers , Male , Materials Testing , Nanostructures , Prostheses and Implants , Rats , Rats, Sprague-Dawley , Surface Properties , Zirconium/chemistry , Zirconium/pharmacologyABSTRACT
Surgical site infections (SSIs) account for a massive economic, physiological, and psychological burden on patients and health care providers. Sutures provide a surface to which bacteria can adhere, proliferate, and promote SSIs. Current methods for fighting SSIs involve the use of sutures coated with common antibiotics (triclosan). Unfortunately, these antibiotics have been rendered ineffective due to the increasing rate of antibiotic resistance. A promising new avenue involves the use of metallic nanoparticles (MNPs). MNPs exhibit low cytotoxicity and a strong propensity for killing bacteria while evading the typical antibiotic resistance mechanisms. In this work, we developed a novel MNPs dip-coating method for PDS-II sutures and explored the capabilities of a variety of MNPs in killing bacteria while retaining the cytocompatibility. Our findings indicated that our technique provided a homogeneous coating for PDS-II sutures, maintaining the strength, structural integrity, and degradability. The MNP coatings possess strong in vitro antibacterial properties against P aeruginosa and S. aureus-varying the %of dead bacteria from ~ 40% (for MgO NPs) to ~ 90% (for Fe2O3) compared to ~ 15% for uncoated PDS-II suture, after 7 days. All sutures demonstrated minimal cytotoxicity (cell viability > 70%) reinforcing the movement towards the use MNPs as a viable antibacterial technology.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents, Local/administration & dosage , Bacterial Infections/prevention & control , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/pharmacology , Metal Nanoparticles , Surgical Wound Infection/prevention & control , Sutures , Technology, Pharmaceutical/methods , Triclosan/administration & dosage , Bacterial Infections/etiology , Drug Resistance, Bacterial , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Surgical Wound Infection/etiology , Sutures/adverse effects , Sutures/microbiologyABSTRACT
BACKGROUND: Drug coated balloons (DCB) with paclitaxel (Ptx) dose of 2-3.5 µg/mm2 balloon surface inhibit restenosis with different effectiveness and duration of success. A clinical dose finding study is not known for any of the currently marketed products. The aim of the present preclinical trial was to investigate a novel DCB coated with 6 µg Ptx/mm2 in a porcine model. METHODS AND RESULTS: The current study investigated a DCB with a novel, modified iopromide based matrix with 6 µg Ptx/mm2. Drug transfer to the vessel wall of peripheral arteries was compared with a dose of 3 µg Ptx/mm2 and two fully overlapping DCB with 3 µg Ptx/mm2, each. Ptx concentration in the vessel wall after drug transfer was about twice as high for balloons with 6 µg/mm2 (1957±1472 µg/g) and two overlapping DCB with 3 µg Ptx/mm2, each (1287±619 µg/g) compared to a single balloon with 3 µg Ptx/mm2, (787±738 µg/g), with statistical significant differences for 1x6 µg/mm2 vs. 1x3 µg/mm2 (p = 0.017) but not for 2x3 µg/mm2 vs. 1x3 µg/mm2 (p = 0.184) and 1x6 µg/mm2 vs. 2x3 µg/mm2 (p = 0.178). The proportion of residual Ptx on balloon after treatment was similar for all groups between 6±1% and 10±3% of dose on balloon. CONCLUSION: The dose of 6 µg Ptx/mm2 was successfully as well as reproducibly coated on conventional balloon catheters. Increased Ptx on balloons resulted in increased drug concentration in the vessel wall. A single balloon with 6 µg Ptx/mm2 seems to provide double dose compared to 3 µg Ptx/mm2, facilitates the procedure, and may reduce medico-economic cost compared to the use of two standard DCB.
Subject(s)
Angioplasty, Balloon/methods , Cardiovascular Agents/administration & dosage , Coated Materials, Biocompatible/administration & dosage , Paclitaxel/administration & dosage , Peripheral Arterial Disease/drug therapy , Vascular Access Devices , Animals , SwineABSTRACT
Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Peri-Implantitis/prevention & control , Peri-Implantitis/therapy , Titanium/pharmacology , Amines/administration & dosage , Amines/chemistry , Amines/pharmacology , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Biofilms/growth & development , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Dental Implants , Drug Stability , Humans , In Vitro Techniques , Male , Materials Testing , Osseointegration/drug effects , Peri-Implantitis/microbiology , Porosity , Rabbits , Surface Properties , Titanium/administration & dosage , Titanium/chemistrySubject(s)
Cardiovascular Agents/administration & dosage , Ischemia , Lower Extremity/blood supply , Paclitaxel/administration & dosage , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/surgery , Aged , Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/instrumentation , Cardiovascular Agents/adverse effects , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/adverse effects , Drug-Eluting Stents/adverse effects , Female , Humans , Ischemia/drug therapy , Ischemia/etiology , Ischemia/mortality , Ischemia/surgery , Lower Extremity/surgery , Male , Paclitaxel/adverse effects , Patient Safety , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/mortality , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Several generations of poly(ß-amino ester) (PBAE) polymers have been developed for efficient cellular transfection. However, PBAE-based gene vectors, similar to other cationic materials, cannot readily provide widespread gene transfer in the brain due to adhesive interactions with the extracellular matrix (ECM). We thus engineered eight vector candidates using previously identified lead PBAE polymer variants but endowed them with non-adhesive surface coatings to facilitate their spread through brain ECM. Specifically, we screened for the ability to provide widespread gene transfer in tumor spheroids and healthy mouse brains. We then confirmed that a lead formulation provided widespread transgene expression in orthotopically established brain tumor models with an excellent in vivo safety profile. Lastly, we developed a method to store it long-term while fully retaining its brain-penetrating property. This new platform provides a broad utility in evaluating novel genetic targets for gene therapy of brain tumors and neurological disorders in preclinical and clinical settings. Graphical abstract We engineered biodegradable DNA-loaded brain-penetrating nanoparticles (DNA-BPN) possessing small particle diameters (< 70 nm) and non-adhesive surface coatings to facilitate their spread through brain tumor extracellular matrix (ECM). These DNA-BPN provide widespread gene transfer in models recapitulating the ECM barrier, including three-dimensional multicellular tumor spheroids and mice with orthotopically established brain tumor.
Subject(s)
Brain Neoplasms/genetics , DNA/administration & dosage , Genetic Therapy/methods , Polymers/chemistry , Animals , Cell Line, Tumor , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , DNA/chemistry , Extracellular Matrix/chemistry , Female , Gene Expression , Humans , Mice , Nanoparticles , Particle Size , Transfection , Xenograft Model Antitumor AssaysABSTRACT
Zinc coated with nanostructured ZnO flowers has received increasing attention as a versatile biomaterial for medical applications. Whatsoever, the potential of these materials to meet specific medical requirements must be explored. Despite in its infancy, surface functionalization is the key strategy to achieve this goal. The functionalization, successfully achieved with cooper (Cu), iron (Fe) or manganese (Mn) oxides (Ox), was highly dependent on the presence of the flowered structures, with the deep physicochemical characterization of these new surfaces revealing specific metal oxide distributions. The functionalization with these metal oxides resulted in distinct biological and in vitro behaviours. The biological response, assessed by fibroblast viability, hemocompatibility, and chick chorioallantoic membrane (CAM), further supported by the in vitro degradation studies, evaluated by immersion and electrochemical techniques, revealed that the deleterious role of CuOx functionalization brought potential for anti-cancer applications; with an antagonist behaviour, the functionalization with MnOx, and in a less extent with FeOx, can be used to favour wound healing in traumatic processes. Despite the possible correlation between biocompatibility and hydroxyapatite precipitation, no correlation could be drawn with the corrosion activity of these surfaces. Overall, the minor addition of relevant physiological as Cu, Fe or Mn oxides resulted in antagonist in vitro responses that can be used as expedite strategies to modulate the behaviour of Zn-based materials, contributing in this way for the design of anti-cancer or wound healing therapies.
Subject(s)
Chorioallantoic Membrane/drug effects , Coated Materials, Biocompatible/administration & dosage , Fibroblasts/drug effects , Hemolysis/drug effects , Manganese Compounds/chemistry , Oxides/chemistry , Zinc Oxide/chemistry , Animals , Coated Materials, Biocompatible/chemistry , Copper/chemistry , Fibroblasts/cytology , Humans , Iron/chemistry , Materials Testing , MiceABSTRACT
OBJECTIVE: Experimental assessment of the effect of modified and unmodified surgical suture material on abdominal adhesive process. MATERIAL AND METHODS: The study was performed on male rats of the Wistar subpopulation. There were 5 animals in each group. In all animals, midline abdominal incision was followed by suturing the parietal peritoneum with modified and unmodified suture material. All animals were euthanized with carbon dioxide vapors in 14 days after surgery. Macro- and microscopic assessment of severity of abdominal adhesive process was carried out. Two types of preparation of excised complexes 'peritoneum-suture material-adhesion' were applied for histological examination: paraffin sections and embedding in epoxy resin. Specimens were stained by Van Gieson and with methylene blue solution. Histological specimens were examined using Axio Imager A1 light microscope (Zeiss, Germany). RESULTS: Polypropylene filaments result extensive adhesions occupying about 75% of the area. Adhesions have a dense structure with signs of vascularization. Modification of suture material with solution of polyhydroxybutyrate/hydroxyvalerate and heparin reduce severity of adhesions. The use of modified suture material was followed by adhesions with more loose structure, no signs of vascularization. Adhesions occupied less than 25% of the area. Histological examination of excised complexes 'peritoneum-suture material-adhesion' revealed accumulation of inflammatory cells around the unmodified suture material, while there were no signs of tissue inflammatory process around the modified sutures. CONCLUSION: Application of polyhydroxybutyrate/hydroxyvalerate and heparin on the surface of surgical sutures is an effective method for prevention of abdominal adhesions.
Subject(s)
Biocompatible Materials/adverse effects , Heparin/administration & dosage , Polyesters/administration & dosage , Polypropylenes/adverse effects , Sutures/adverse effects , Tissue Adhesions/prevention & control , Animals , Biocompatible Materials/administration & dosage , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/adverse effects , Disease Models, Animal , Heparin/adverse effects , Male , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/prevention & control , Peritoneum/blood supply , Peritoneum/pathology , Peritoneum/surgery , Polyesters/adverse effects , Polypropylenes/administration & dosage , Rats , Rats, Wistar , Tissue Adhesions/etiology , Tissue Adhesions/pathologyABSTRACT
BACKGROUND: Large segmental bone defects are still one of the challenges for orthopaedic surgeons. Although 3D-printed porous titanium is a potential bone substitute material because of its porous structure simulating natural bone, the titanium surface has low bioactivity, integrates with bone tissue through the simple mechanical interlock. The study aims to investigate the capability and osteogenesis of 3D-printed porous titanium (3D PPT)-coated polydopamine (PDA) for repairing bone defects. METHODS: Fifteen 6-month New Zealand white rabbits were implanted with PDA-3D PPT to repair 6 mm × 10 mm defects on the femoral condyle compared with the group of 3D PPT and comparing with the blank group. After 6 weeks and 12 weeks, micro-CT and histological examination were performed to observe bone growth. RESULTS: All the PDA-3D PPT group, the 3D PPT group and the blank group recovered in good condition. The images showed that the boundaries between the implant area and the surrounding area were obscure in the three groups. The results of micro-CT demonstrated that at 6 weeks and 12 weeks, the bone volume (BV) values of PDA-3D PPT implants group were significantly higher than those of the 3D PPT implants group and blank group (P < 0.05), the BV/tissue volume (TV) and the trabecular number (Tb.N) of PDA-3D PPT implants were significantly higher than those of the 3D PPT group and blank group (P < 0.05). The results of un-decalcified bone slicing showed that ore new bone appeared to form around the PDA-3D PPT than that of 3D PPT and blank group. The bone-implant contact (BIC) of PDA-3D PPT was better (P < 0.05) than that of 3D PPT group. CONCLUSION: PDA-3D PPT could improve the bioactivity and promote the growth and healing of bone tissue and can be a promising repairing material.
Subject(s)
Bone Substitutes/administration & dosage , Coated Materials, Biocompatible/administration & dosage , Femur/surgery , Indoles/administration & dosage , Polymers/administration & dosage , Printing, Three-Dimensional , Titanium/administration & dosage , Animals , Femur/diagnostic imaging , Male , Rabbits , X-Ray Microtomography/methodsABSTRACT
Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.
Subject(s)
Electrochemical Techniques/methods , Needles , Ovalbumin , Polylactic Acid-Polyglycolic Acid Copolymer , Administration, Cutaneous , Animals , Cells, Cultured , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacokinetics , Dendritic Cells , Female , Humans , Mice , Mice, Inbred C57BL , Microinjections/instrumentation , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Ovalbumin/administration & dosage , Ovalbumin/chemistry , Ovalbumin/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokineticsABSTRACT
The use of red blood cell (RBC) membrane coatings has recently been found to be a biomimetic strategy to confer inner core nanomaterials with improved pharmacokinetic profiles by utilizing the intrinsic long blood circulation time of RBCs. Here, we envelope superparamagnetic nanoclusters (MNCs) with RBC membrane ghosts to obtain MNC@RBCs with significantly improved physiological stability compared to that of bare MNCs. After being loaded with near-infrared (NIR) cypate molecules, the as-prepared Cyp-MNC@RBCs show remarkably increased NIR absorbance and resultant efficient photothermal conversion efficacy. By tracking the NIR fluorescence of cypate in an in vivo fluorescence imaging system, we uncover that such Cyp-MNC@RBCs upon intravenous injection show significantly improved tumor-homing capacity as compared to bare cypate-loaded MNCs. A similar result is further evidenced by recording the T2-weighted magnetic resonance imaging (MRI) signal of MNCs. Furthermore, upon exposure to 808 nm laser irradiation, the tumors grown on the mice with the intravenous injection of Cyp-MNC@RBCs show a higher temperature increase than the tumors grown on the mice injected with plain MNC@RBCs and thus are significantly suppressed via photothermal ablation. This study presents the preparation of biomimetic Cyp-MNC@RBCs with greatly improved tumor-homing capacity as multifunctional nanotheranostic agents for fluorescence and MRI bimodal imaging-guided cancer photothermal therapy.
Subject(s)
Coated Materials, Biocompatible/therapeutic use , Erythrocytes/chemistry , Indoles/therapeutic use , Magnetite Nanoparticles/chemistry , Multimodal Imaging , Photothermal Therapy , Propionates/therapeutic use , Animals , Cell Membrane/chemistry , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Female , HCT116 Cells , Humans , Indoles/administration & dosage , Indoles/chemistry , Lasers , Magnetite Nanoparticles/administration & dosage , Materials Testing , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms, Experimental/diagnostic imaging , Neoplasms, Experimental/therapy , Propionates/administration & dosage , Propionates/chemistryABSTRACT
PURPOSE: The study aimed to evaluate the histologic properties and infection resistance of three different mesh materials in a rat model. METHODS: Each mesh, in both infectious (n = 96) and non-infectious groups (n = 270), was positioned both in sublay (preperitoneally) and onlay (subcutaneously) locations. Properties of the biological (Surgisis; Cook Surgical), composite, partially resorbing (Vypro II mesh; Ethicon) and non-resorbing (TiMesh; GFE Medizintechnik GmbH) mesh were evaluated and compared. Animals were killed at 7, 21 and 90 days after implantation. The following parameters were evaluated to assess the host response to the mesh material: inflammation, vascularization, fibrosis, collagen formation, Ki67, and a foreign body reaction by granuloma formation (FBG). RESULTS: Surgisis mesh produced more pronounced inflammation and cell proliferation, and less intense granuloma formation, as well as fibrosis, compared to the other two groups. When the infected materials were examined, we found signs of local infection to be more often present in Surgisis group of animals. CONCLUSIONS: In the presence of bacterial contamination, no benefits were observed in the use of the Surgisis prosthesis over the use of TiMesh and Vypro II.
Subject(s)
Prosthesis Implantation/methods , Prosthesis-Related Infections/etiology , Staphylococcal Infections/etiology , Surgical Mesh , Animals , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/adverse effects , Collagen/administration & dosage , Collagen/adverse effects , Disease Models, Animal , Fibrosis/etiology , Foreign-Body Reaction/etiology , Inflammation/etiology , Male , Polyglactin 910/administration & dosage , Polyglactin 910/adverse effects , Polypropylenes/administration & dosage , Polypropylenes/adverse effects , Prosthesis Implantation/adverse effects , Prosthesis-Related Infections/microbiology , Rats , Rats, Wistar , Staphylococcus aureus , Surgical Mesh/adverse effects , Titanium/administration & dosage , Titanium/adverse effectsABSTRACT
Due to their unique optical properties upconversion nanoparticles (UCNPs) provide exceptionally high contrast for imaging of true nanoparticle distribution in excised human skin. It makes possible to show penetration of solid nanoparticles in skin treated with chemical enhancers. We demonstrated tracing upconversion nanoparticles in excised human skin by means of optical microscopy at the discrete particle level sensitivity to obtain their penetration profiles, which was validated by laser-ablation inductively-coupled-plasma mass-spectrometry. To demonstrate utilities of our method, UCNPs were coated with polymers, formulated in water and chemical enhancers, and applied on excised human skin mounted on Franz cells, followed by imaging using a custom-built laser-scanning microscope. To evaluate the toxicity impact on skin by polymer-coated UCNPs, we introduced a tissue engineering model of viable epidermis made of decellularized chick embryo skin seeded with keratinocytes. UCNPs formulated in water stopped in stratum corneum, whereas UCNPs formulated in ethanol-water solution crossed stratum corneum and reached viable epidermis - hence, the enhancement effect for solid nanoparticles was detected by optical microscopy. All polymer-coated UCNPs were found nontoxic within the accepted safety levels. The keratinocyte resilience to polyethyleneimine-coated UCNPs was surprising considering cytotoxicity of polyethyleneimine to two-dimensional cell cultures.
Subject(s)
Coated Materials, Biocompatible/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Skin/metabolism , Animals , Cell Line , Cell Tracking/methods , Chick Embryo , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/pharmacokinetics , Epidermis/metabolism , Humans , Keratinocytes/metabolism , Microscopy, Confocal , Microscopy, Electron, Transmission , Molecular Imaging/methods , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Oxazines/chemistry , Polymers/administration & dosage , Polymers/pharmacokinetics , Skin/cytologySubject(s)
Annulus Fibrosus/metabolism , Coated Materials, Biocompatible/chemical synthesis , Polyurethanes/chemical synthesis , Tissue Adhesives/chemical synthesis , Animals , Cell Line , Cell Survival/drug effects , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/metabolism , Collagen/chemistry , Haplorhini , Injections , Kinetics , Mechanical Phenomena , Mice , Polycarboxylate Cement/chemistry , Polyurethanes/administration & dosage , Polyurethanes/metabolism , Surface Properties , Temperature , Thermodynamics , Tissue Adhesions/metabolism , Tissue Adhesives/administration & dosage , Tissue Adhesives/metabolism , ViscosityABSTRACT
Poor control towards glycemic levels among diabetic patients may lead to severe micro/macro-vascular and neuropathic complexities. Proper functioning of alpha-beta cells of pancreases is required to attain long term glycemic control among type 2 diabetics. The recent developments to manage diabetes are focused on controlling the insulin-glucagon secretions from the pancreases. DPP-4 inhibitors class of drugs after elevating GLP-1/GIP (incretins) levels in the blood, not only raise the insulin levels but also suppress the glucagon level. Vildagliptin (VI) is a potent DPP-4 inhibitor with least adverse events compared to other DPP-4 inhibitors. We encapsulated VI into 3D nanocube that gets bind to the DNA due to secondary amine in its chemical structure. DNA-nanocube being negatively charged was incubated with the PLL to attain positive surface. Ultimately VI loaded nanocubes were coated with the negatively charged Na-alginate via electrostatic attraction method to get stable spherical nanospheres for oral delivery of VI. Nanospheres were evaluated physically through native PAGE analysis, DSC, TGA, dissolution testing, XRD and FTIR. We attained uniformed and spherical nanospheres with stable topology, nanoscale size precision (40-150 nm in diameter), Entrapment efficiency (up to 90%), prolonged drug release (13 ± 4 h) at basic pH, and superior oral antidiabetic effects with improved GLP1 and glycemic levels. The formulated nanospheres attained size uniformity and better therapeutic outcomes in terms of reduced adverse events and better control of glycemic levels than previously reported methods with decreased dosage frequency tested in Db/Db mice.
Subject(s)
Alginates/chemistry , Coated Materials, Biocompatible/chemistry , DNA/chemistry , Diabetes Mellitus, Type 2/drug therapy , Drug Design , Hypoglycemic Agents/therapeutic use , Nanoparticles/chemistry , Vildagliptin/therapeutic use , Administration, Oral , Alginates/administration & dosage , Animals , Coated Materials, Biocompatible/administration & dosage , DNA/administration & dosage , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Mice , Nanoparticles/administration & dosage , Vildagliptin/administration & dosage , Vildagliptin/chemistryABSTRACT
PURPOSE: In view of a recent meta-analysis reporting increased mortality following angioplasty with paclitaxel-coated devices in peripheral arteries, we performed a patient-level 2-year mortality analysis based on pooled original data of four randomized controlled trials (THUNDER, FEMPAC, PACIFIER and CONSEQUENT). METHODS AND RESULTS: Clinical data of four randomized controlled trial were pooled to assess 2-year mortality following paclitaxel-coated balloon (PCB) angioplasty compared to angioplasty without paclitaxel (control group). A logistic regression model was applied to identify potential predictors of mortality. At two years, 13 of 185 (7.0%) patients had died in the control group and 16/184 (8.7%) in the PBC group, p = 0.55. Kaplan-Meier analysis revealed no significant difference from all-cause death at 2 years (log rank p = 0.54). Causes of death were well balanced between the groups with no pattern or trend in favour of any specific causes in the PBC group. Logistic regression revealed that treatment groups (controls or PBC) were not a predictor of 2-year mortality. The only predictor for mortality was patient age ≥ 75 years. The delivered paclitaxel doses per patient were not significantly different in patients that died and those who did not die during the 24-month follow-up (5.300 ± 4.224 µg vs. 6.248 ± 4.629 µg, p = 0.433). CONCLUSIONS: Based on original patient-level data of four pooled randomized controlled trials, we found no increase in 2-year mortality in patients treated with PCB compared to control patients treated with uncoated balloons. Causes of death were well balanced between PCB and control patients.
Subject(s)
Angioplasty, Balloon/methods , Coated Materials, Biocompatible/therapeutic use , Femoral Artery/pathology , Paclitaxel/therapeutic use , Popliteal Artery/pathology , Vascular Neoplasms/therapy , Age Factors , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Coated Materials, Biocompatible/administration & dosage , Databases, Factual , Equipment Design , Female , Follow-Up Studies , Germany , Humans , Kaplan-Meier Estimate , Male , Paclitaxel/administration & dosage , Prospective Studies , Treatment Outcome , Vascular Neoplasms/pathologyABSTRACT
Antibacterial and osteogenic design is required for ideal orthopedic implants. The excellent antimicrobial performance of silver nanoparticles (AgNPs) has attracted interest for the treatment of implant-related infections. However, the dose-dependent cytotoxicity of silver and its negative impact on bone implants restrict the further use of AgNPs coatings. Therefore, a hybrid coating containing polydopamine (PDA), hydroxyapatite (HA), AgNPs, and chitosan (CS) is prepared. Organic chelators CS and PDA that have promising biocompatibility are used to prevent the rapid release of silver ions from the AgNPs coating. The double chelating effect of PDA and CS significantly reduces silver ion release from the hybrid coating. The coating exhibits excellent anti-biofilm efficiency of 91.7%, 89.5%, and 92.0% for Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli, respectively. In addition, the coating can significantly stimulate osteogenic differentiation of MC3T3-E1 cells and promote bone-implant osseointegration in vivo as compared to that in the control group. The longitudinal biosafety of the coating is confirmed in vivo by histological evaluation and blood tests. The results of this study indicate that the hybrid coating exhibits antibacterial properties as well as allow bone-implant osseointegration, thereby providing insight into the design of multifunctional implants for long-term orthopedic applications.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Coated Materials, Biocompatible/administration & dosage , Metal Nanoparticles/administration & dosage , Silver/administration & dosage , 3T3 Cells , Animals , Anti-Bacterial Agents/chemistry , Cell Differentiation/drug effects , Cell Line , Chitosan/administration & dosage , Chitosan/chemistry , Coated Materials, Biocompatible/chemistry , Durapatite/administration & dosage , Durapatite/chemistry , Female , Indoles/administration & dosage , Indoles/chemistry , Metal Nanoparticles/chemistry , Mice , Osteogenesis/drug effects , Polymers/administration & dosage , Polymers/chemistry , Rats , Rats, Sprague-Dawley , Silver/chemistryABSTRACT
Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.
Subject(s)
Absorbable Implants , Coronary Vessels/surgery , Drug-Eluting Stents , Polymers/chemistry , Animals , Cardiovascular Agents/administration & dosage , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Coronary Angiography/methods , Coronary Artery Disease/surgery , Endothelial Cells/metabolism , Everolimus/administration & dosage , Everolimus/chemistry , Fibrin/metabolism , Models, Animal , Percutaneous Coronary Intervention , Polymers/administration & dosage , Polymers/adverse effects , Prosthesis Design , Sirolimus/administration & dosage , Sirolimus/chemistry , Swine , Swine, Miniature , Thrombosis/etiology , Thrombosis/metabolism , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS:: Stenosis due to intimal hyperplasia and restenosis after initially successful percutaneous angioplasty are common reasons for failing arteriovenous fistulas. The aim of this study was to evaluate the effect of drug-coated balloons in the treatment of arteriovenous fistula stenosis. DESIGN:: Single-center, parallel group, randomized controlled trial. Block randomized by sealed envelope 1:1. MATERIALS AND METHODS:: A total of 39 patients with primary or recurrent stenosis in a failing native arteriovenous fistulas were randomized to drug-coated balloon (n = 19) or standard balloon angioplasty (n = 20). Follow-up was 1 year. Primary outcome measure was target lesion revascularization. RESULTS:: In all, 36 stenoses were analyzed; three patients were excluded due to technical failure after randomization. A total of 88.9% (16/18) in the drug-coated balloon group was revascularized or occluded within 1 year, compared to 22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110 and 193 days after the drug-coated balloon and balloon angioplasty, respectively (p = 0.06). CONCLUSIONS:: With 1-year follow-up, the target lesion revascularization-free survival after drug-coated balloon-treatment was clearly worse. The reason for this remains unknown, but it may be due to differences in the biological response to paclitaxel in the venous arteriovenous fistula-wall compared to its antiproliferative effect in the arterial wall after drug-coated balloon treatment of atherosclerotic occlusive lesions. Trial registration: ClinicalTrials.gov NCT03036241.
Subject(s)
Angioplasty, Balloon/methods , Arteriovenous Shunt, Surgical/adverse effects , Cardiovascular Agents/administration & dosage , Paclitaxel/administration & dosage , Vascular Patency/drug effects , Venous Insufficiency/therapy , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon/instrumentation , Cardiovascular Agents/adverse effects , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/adverse effects , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/therapy , Male , Middle Aged , Paclitaxel/adverse effects , Prospective Studies , Renal Dialysis/methods , Venous Insufficiency/drug therapy , Venous Insufficiency/etiologyABSTRACT
PURPOSE: This study investigated whether Escherichia coli-derived bone morphogenetic protein (BMP)-2 (E-BMP-2) adsorbed onto ß-tricalcium phosphate (ß-TCP) granules can induce bone regeneration in critical-size femoral segmental defects in rabbits. METHODS: Bone defects 20 mm in size and stabilized with an external fixator were created in the femur of New Zealand white rabbits, which were divided into BMP-2 and control groups. E-BMP-2-loaded ß-TCP granules were implanted into defects of the BMP-2 group, whereas defects in the controls were implanted with ß-TCP granules alone. At 12 and 24 weeks after surgery, radiographs were obtained of the femurs and histological and biomechanical assessments of the defect area were performed. Bone regeneration was quantified using micro-computed tomography at 24 weeks. RESULTS: Radiographic and histologic analyses revealed bone regeneration in the BMP-2 group but not the control group; no fracturing of newly formed bone occurred when the external fixator was removed at 12 weeks. At 24 weeks, tissue mineral density, the ratio of bone volume to total volume, and volumetric bone mineral density of the callus were higher in the BMP-2 group than in control animals. In the former, ultimate stress, extrinsic stiffness, and failure energy measurements for the femurs were higher at 24 weeks than at 12 weeks. CONCLUSION: E-BMP-2-loaded ß-TCP granules can effectively promote bone regeneration in long bone defects.