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1.
Molecules ; 26(13)2021 Jul 02.
Article in English | MEDLINE | ID: mdl-34279396

ABSTRACT

The main strategies against Triatoma infestans (primary vector responsible for the Chagas disease transmission) are the elimination or reduction of its abundance in homes through the application of insecticides or repellents with residual power, and environmental management through the improvement of housing. The use of plant-derived compounds as a source of therapeutic agents (i.e., essential oils from aromatic plants and their components) is a valuable alternative to conventional insecticides and repellents. Essential oil-based insect repellents are environmentally friendly and provide reliable personal protection against the bites of mosquitoes and other blood-sucking insects. This study investigates, for the first time to our knowledge, the potential repellent activity of Zuccagnia punctata essential oil (ZEO) and poly(ε-caprolactone) matrices loaded with ZEO (ZEOP) prepared by solvent casting. The analysis of its essential oil from aerial parts by GC-FID and GC-MS, MS allowed the identification of 25 constituents representing 99.5% of the composition. The main components of the oil were identified as (-)-5,6-dehydrocamphor (62.4%), alpha-pinene (9.1%), thuja-2, 4 (10)-diene (4.6%) and dihydroeugenol (4.5%). ZEOP matrices were homogeneous and opaque, with thickness of 800 ± 140 µm and encapsulation efficiency values above 98%. ZEO and ZEOP at the lowest dose (0.5% wt./wt., 96 h) showed a repellency of 33 and 73% respectively, while at the highest dose (1% wt./wt., 96 h) exhibited a repellent activity of 40 and 66 %, respectively. On the other hand, until 72 h, ZEO showed a strong repellent activity against T. infestans (88% repellency average; Class V) to both concentrations, compared with positive control N-N diethyl-3-methylbenzamide (DEET). The essential oils from the Andean flora have shown an excellent repellent activity, highlighting the repellent activity of Zuccagnia punctata. The effectiveness of ZEO was extended by its incorporation in polymeric systems and could have a potential home or peridomiciliary use, which might help prevent, or at least reduce, Chagas' disease transmission.


Subject(s)
Fabaceae/chemistry , Insect Repellents/pharmacology , Mosquito Vectors/drug effects , Oils, Volatile/pharmacology , Triatoma/drug effects , Animals , Camphor/analogs & derivatives , Camphor/analysis , Eugenol/analogs & derivatives , Eugenol/analysis , Insect Repellents/chemistry , Oils, Volatile/chemistry , Polyesters/chemistry
2.
Molecules ; 26(13)2021 Jun 24.
Article in English | MEDLINE | ID: mdl-34202602

ABSTRACT

In this work, we report the electrospinning and mechano-morphological characterizations of scaffolds based on blends of a novel poly(ester urethane urea) (PHH) and poly(dioxanone) (PDO). At the optimized electrospinning conditions, PHH, PDO and blend PHH/PDO in Hexafluroisopropanol (HFIP) solution yielded bead-free non-woven random nanofibers with high porosity and diameter in the range of hundreds of nanometers. The structural, morphological, and biomechanical properties were investigated using Differential Scanning Calorimetry, Scanning Electron Microscopy, Atomic Force Microscopy, and tensile tests. The blended scaffold showed an elastic modulus (~5 MPa) with a combination of the ultimate tensile strength (2 ± 0.5 MPa), and maximum elongation (150% ± 44%) in hydrated conditions, which are comparable to the materials currently being used for soft tissue applications such as skin, native arteries, and cardiac muscles applications. This demonstrates the feasibility of an electrospun PHH/PDO blend for cardiac patches or vascular graft applications that mimic the nanoscale structure and mechanical properties of native tissue.

3.
Nanotechnology ; 31(17): 172002, 2020 Apr 24.
Article in English | MEDLINE | ID: mdl-31931493

ABSTRACT

The development of three-dimensional (3D) scaffolds with physical and chemical topological cues at the macro-, micro-, and nanometer scale is urgently needed for successful tissue engineering applications. 3D scaffolds can be manufactured by a wide variety of techniques. Electrospinning technology has emerged as a powerful manufacturing technique to produce non-woven nanofibrous scaffolds with very interesting features for tissue engineering products. However, electrospun scaffolds have some inherent limitations that compromise the regeneration of thick and complex tissues. By integrating electrospinning and other fabrication technologies, multifunctional 3D fibrous assemblies with micro/nanotopographical features can be created. The proper combination of techniques leads to materials with nano and macro-structure, allowing an improvement in the biological performance of tissue-engineered constructs. In this review, we focus on the most relevant strategies to produce electrospun polymer/composite scaffolds with 3D architecture. A detailed description of procedures involving physical and chemical agents to create structures with large pores and 3D fiber assemblies is introduced. Finally, characterization and biological assays including in vitro and in vivo studies of structures intended for the regeneration of functional tissues are briefly presented and discussed.


Subject(s)
Tissue Engineering/methods , Tissue Scaffolds/chemistry , Electrochemistry , Nanofibers/chemistry , Polymers/chemistry , Porosity
4.
J Mater Sci Mater Med ; 31(11): 105, 2020 Nov 03.
Article in English | MEDLINE | ID: mdl-33141369

ABSTRACT

3D printing has emerged as vanguard technique of biofabrication to assemble cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissues. In this work, gelatin methacrylate (GelMA)/alginate hydrogel scaffolds were obtained by 3D printing and 14-3-3ε protein was encapsulated in the hydrogel to induce osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASC). GelMA/alginate-based grid-like structures were printed and remained stable upon photo-crosslinking. The viscosity of alginate allowed to control the pore size and strand width. A higher viscosity of hydrogel ink enhanced the printing accuracy. Protein-loaded GelMA/alginate-based hydrogel showed a clear induction of the osteogenic differentiation of hASC cells. The results are relevant for future developments of GelMA/alginate for bone tissue engineering given the positive effect of 14-3-3ε protein on both cell adhesion and proliferation.


Subject(s)
14-3-3 Proteins/chemistry , Hydrogels/chemistry , Osteogenesis/physiology , Printing, Three-Dimensional , Adipose Tissue/metabolism , Alginates/chemistry , Cell Adhesion , Cell Differentiation , Cell Proliferation , Cross-Linking Reagents , Gelatin , Humans , Ink , Mesenchymal Stem Cells/metabolism , Methacrylates/chemistry , Osteogenesis/drug effects , Recombinant Proteins/chemistry , Viscosity
5.
Polymers (Basel) ; 16(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38794507

ABSTRACT

This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery native vessels. Two segmented polyurethanes were synthesized using lysine (SPUUK) and ascorbic acid (SPUAA), and the resulting materials were used to create the intima and adventitia layers, respectively. In contrast, the media layer of the TVG was composed of a commercially available polyurethane, Pearlbond 703 EXP. For comparison purposes, single-layer vascular grafts (SVGs) from individual polyurethanes and a polyurethane blend (MVG) were made and tested similarly and evaluated according to the ISO 7198 standard. The TVG exhibited the highest circumferential tensile strength and longitudinal forces compared to single-layer vascular grafts of lower thicknesses made from the same polyurethanes. The TVG also showed higher suture and burst strength values than native vessels. The TVG withstood up to 2087 ± 139 mmHg and exhibited a compliance of 0.15 ± 0.1%/100 mmHg, while SPUUK SVGs showed a compliance of 5.21 ± 1.29%/100 mmHg, akin to coronary arteries but superior to the saphenous vein. An indirect cytocompatibility test using the MDA-MB-231 cell line showed 90 to 100% viability for all polyurethanes, surpassing the minimum 70% threshold needed for biomaterials deemed cytocompatibility. Despite the non-cytotoxic nature of the polyurethane extracts when grown directly on the surface, they displayed poor fibroblast adhesion, except for SPUUK. All vascular grafts showed hemolysis values under the permissible limit of 5% and longer coagulation times.

6.
Pharmaceutics ; 15(7)2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37514150

ABSTRACT

Antimicrobial resistance (AMR) developed by microorganisms is considered one of the most critical public health issues worldwide. This problem is affecting the lives of millions of people and needs to be addressed promptly. Mainly, antibiotics are the substances that contribute to AMR in various strains of bacteria and other microorganisms, leading to infectious diseases that cannot be effectively treated. To avoid the use of antibiotics and similar drugs, several approaches have gained attention in the fields of materials science and engineering as well as pharmaceutics over the past five years. Our focus lies on the design and manufacture of polymeric-based materials capable of incorporating antimicrobial agents excluding the aforementioned substances. In this sense, two of the emerging techniques for materials fabrication, namely, electrospinning and 3D printing, have gained significant attraction. In this article, we provide a summary of the most important findings that contribute to the development of antimicrobial systems using these technologies to incorporate various types of nanomaterials, organic molecules, or natural compounds with the required property. Furthermore, we discuss and consider the challenges that lie ahead in this research field for the coming years.

7.
RSC Adv ; 13(23): 15960-15974, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37250225

ABSTRACT

This study seeks to simulate both the chemistry and piezoelectricity of bone by synthesizing electroconductive silane-modified gelatin-poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) scaffolds using the freeze drying technique. In order to enhance hydrophilicity, cell interaction, and biomineralization, the scaffolds were functionalized with polydopamine (PDA) inspired by mussels. Physicochemical, electrical, and mechanical analyses were conducted on the scaffolds, as well as in vitro evaluations using the osteosarcoma cell line MG-63. It was found that scaffolds had interconnected porous structures, so the PDA layer formation reduced the size of pores while maintaining scaffold uniformity. PDA functionalization reduced the electrical resistance of the constructs while improving their hydrophilicity, compressive strength, and modulus. As a result of the PDA functionalization and the use of silane coupling agents, higher stability and durability were achieved as well as an improvement in biomineralization capability after being soaked in SBF solution for a month. Additionally, the PDA coating enabled the constructs to enhance viability, adhesion, and proliferation of MG-63 cells, as well as to express alkaline phosphatase and deposit HA, indicating that scaffolds can be used for bone regeneration. Therefore, the PDA-coated scaffolds developed in this study and the non-toxic performance of PEDOT:PSS present a promising approach for further in vitro and in vivo studies.

8.
Polymers (Basel) ; 15(4)2023 Feb 04.
Article in English | MEDLINE | ID: mdl-36850078

ABSTRACT

The development of accurate drug delivery systems is one of the main challenges in the biomedical field. A huge variety of structures, such as vesicles, nanoparticles, and nanofibers, have been proposed as carriers for bioactive agents, aiming for precision in administration and dosage, safety, and bioavailability. This review covers the use of electrohydrodynamic techniques both for the immobilization and for the synthesis of vesicles in a non-conventional way. The state of the art discusses the most recent advances in this field as well as the advantages and limitations of electrospun and electrosprayed amphiphilic structures as precursor templates for the in situ vesicle self-assembly. Finally, the perspectives and challenges of combined strategies for the development of advanced structures for the delivery of bioactive agents are analyzed.

9.
Biotechnol J ; 18(4): e2200413, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36694286

ABSTRACT

Human Adipose-Derived Mesenchymal Stem/Stromal Cells (hAD-MSCs) have great potential for tissue regeneration. Since transplanted hAD-MSCs are likely to be placed in a hypoxic environment, culturing the cells under hypoxic conditions might improve their post-transplantation survival and regenerative performance. The combination of hAD-MSCs and PCL-nHA nanofibers synergically improves the contribution of both components for osteoblast differentiation. In this work, we hypothesized that this biomaterial constitutes a hypoxic environment for hAD-MSCs. We studied the cellular re-arrangement and the subcellular ultrastructure by Transmission Electron Microscopy (TEM) of hAD-MSCs grown into PCL-nHA nanofibers, and we compared them with the same cells grown in two-dimensional cultures, over tissue culture-treated plastic, or glass coverslips. Among the most evident changes, PCL-nHA grown cells showed enlarged mitochondria, and accumulation of glycogen granules, consistent with a hypoxic environment. We observed a 3.5 upregulation (p = 0.0379) of Hypoxia Inducible Factor (HIF)-1A gene expression in PCL-nHA grown cells. This work evidences for the first time intra-cellular changes in three-dimensional compared to two-dimensional cultures, which are adaptive responses of the cells to an environment more closely resembling that of the in vivo niche after transplantation, thus PCL-nHA nanofibers are adequate for hAD-MSCs pre-conditioning.


Subject(s)
Mesenchymal Stem Cells , Nanofibers , Humans , Tissue Scaffolds/chemistry , Durapatite/chemistry , Durapatite/metabolism , Polyesters/chemistry , Biocompatible Materials/chemistry , Cell Differentiation , Nanofibers/chemistry , Tissue Engineering/methods
10.
Int J Biol Macromol ; 179: 567-575, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33675835

ABSTRACT

One of the main challenges of cardiovascular tissue engineering is the development of bioresorbable and compliant small-diameter vascular grafts (SDVG) for patients where autologous grafts are not an option. In this work, electrospun bilayered bioresorbable SDVG based on blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) were prepared and evaluated. The inner layer of these SDVG was surface-modified with heparin, following a methodology involving PHD urethane functional groups. Heparin was selected as anticoagulant agent, and also due to its ability to promote human umbilical vein endothelial cells (HUVECs) growth and to inhibit smooth muscle cells over-proliferation, main cause of neointimal hyperplasia and restenosis. Immobilized heparin was quantified and changes in SDVG microstructure were investigated through SEM. Tensile properties of the heparin-functionalized SDVG resembled those of saphenous vein. Vascular grafts were seeded with HUVECs and cultured on a flow-perfusion bioreactor to analyze the effect of heparin on graft endothelization under simulated physiological-like conditions. The analysis of endothelial cells attachment and gene expression (Real-Time PCR) pointed out that the surface functionalization with heparin successfully promoted a stable and functional endothelial cell layer.


Subject(s)
Anticoagulants/metabolism , Bioprosthesis , Blood Vessel Prosthesis , Heparin/metabolism , Human Umbilical Vein Endothelial Cells/cytology , Tissue Engineering/methods , Humans , Polyesters/chemistry , Polyurethanes/chemistry
11.
Eur J Pharm Sci ; 156: 105563, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32976956

ABSTRACT

Probiotic products require high number of viable and active microorganisms during storage. In this work, the survival of human vaginal Lactobacillus gasseri CRL1320 and Lactobacillus rhamnosus CRL1332 after nanofiber-immobilization by electrospinning with polyvinyl-alcohol, and during storage was evaluated. The optimization of bacterial immobilization and storage conditions using bioprotectors (skim milk-lactose and glycerol) and oxygen-excluding packaging was carried out, compared with lyophilization. After electrospinning, a higher survival rate of L. rhamnosus (93%) compared to L. gasseri (84%) was obtained in nanofibers, with high viable cells (>107 colony-forming unit/g) of the two probiotics in nanofibers stored at -20°C up to 14 days. The storage in oxygen-excluding packaging was an excellent strategy to extend the shelf-life of L. rhamnosus (up to 1.7 × 108 CFU/g) in nanofibers stored at 4°C during 360 days, with no addition of bioprotectives, resulting similar to freeze-dried-cells. L. rhamnosus was successfully incorporated into polymeric hydrophilic nanofibers with a mean diameter of 95 nm. The composite materials were characterized in terms of morphology, and their physicochemical and thermal properties assessed. Nanofiber-immobilized L. rhamnosus cells maintained the inhibition to urogenital pathogens. Thus, polymeric nanofiber-immobilized L. rhamnosus CRL1332 can be included in vaginal probiotic products to prevent or treat urogenital infections.


Subject(s)
Lacticaseibacillus rhamnosus , Nanofibers , Probiotics , Female , Humans , Lactobacillus , Vagina
12.
J Mater Sci Mater Med ; 20(10): 2129-37, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19434481

ABSTRACT

The development of biomimetic highly-porous scaffolds is essential for successful tissue engineering. Segmented poly(ester urethane)s and poly(ester urethane urea)s have been infrequently used for the fabrication of electrospun nanofibrous tissues, which is surprising because these polymers represent a very large variety of materials with tailored properties. This study reports the preparation of new electrospun elastomeric polyurethane scaffolds. Two novel segmented polyurethanes (SPU), synthesized from poly(epsilon-caprolactone) diol, 1,6-hexamethylene diisocyanate, and diester-diphenol or diurea-diol chain extenders, were used (Caracciolo et al. in J Mater Sci Mater Med 20:145-155, 2009). The spinnability and the morphology of the electrospun SPU scaffolds were investigated and discussed. The electrospinning parameters such as solution properties (polymer concentration and solvent) and processing parameters (applied electric field, needle to collector distance and solution flow rate) were optimized to achieve smooth, uniform bead-free fibers with diameter (~700 nm) mimicking the protein fibers of native extracellular matrix (ECM). The obtained elastomeric polyurethane scaffolds could be appropriate for soft tissue-engineering applications.


Subject(s)
Absorbable Implants , Polyesters/chemical synthesis , Polyurethanes/chemical synthesis , Tissue Engineering/methods , Biomimetic Materials/chemical synthesis , Biomimetic Materials/chemistry , Guided Tissue Regeneration , Models, Biological , Polyesters/chemistry , Polyurethanes/chemistry , Porosity , Soft Tissue Injuries/therapy , Surface Properties , Tissue Scaffolds/chemistry
13.
Int J Pharm ; 523(2): 441-453, 2017 May 25.
Article in English | MEDLINE | ID: mdl-27640245

ABSTRACT

The development of biomimetic highly-porous scaffolds is essential for successful tissue engineering. Electrospun nanofibers are highly versatile platforms for a broad range of applications in different research areas. In the biomedical field, micro/nanoscale fibrous structures have gained great interest for wound dressings, drug delivery systems, soft and hard-tissue engineering scaffolds, enzyme immobilization, among other healthcare applications. In this mini-review, electrospun gelatin-based scaffolds for a variety of tissue engineering applications, such as bone, cartilage, skin, nerve, and ocular and vascular tissue engineering, are reviewed and discussed. Gelatin blends with natural or synthetic polymers exhibit physicochemical, biomechanical, and biocompatibility properties very attractive for scaffolding. Current advances and challenges on this research field are presented.


Subject(s)
Gelatin/chemistry , Tissue Engineering , Tissue Scaffolds , Nanofibers/chemistry , Polymers
14.
J Biomed Mater Res B Appl Biomater ; 105(5): 966-976, 2017 07.
Article in English | MEDLINE | ID: mdl-26856526

ABSTRACT

Electrospun nanocomposite matrices based on poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp) and amoxicillin (AMX) were designed and investigated for dental applications. nHAp provides good biocompatibility, bioactivity, osteoconductivity, and osteoinductivity properties, and AMX, as antibiotic model, controls and/or reduces bacterial contamination of periodontal defects while enhancing tissue regeneration. A series of polymeric nanocomposites was obtained by varying both the antibiotic and nHAp contents. Fibrous membranes of different compositions were obtained by electrospinning technique, and morphological, thermal, mechanical and surface properties were characterized. The incorporation of AMX seemed to alter the nHAp distribution within the microfibrous matrix. The interaction between AMX and nHAp affected the mechanical performance and modulated the antibiotic release behavior. AMX release profiles presented a burst release that depended on nHAp content, followed by a slow release stage where the drug content (85-100%) was released in 3 weeks. The antimicrobial activity of the AMX-loaded membranes was tested with four bacterial strains depended on both the drug and nHAp contents. Extensive mineralization in simulated body fluid (SBF) was evidenced by SEM/EDX analysis after 21 days. The studied electrospun nanocomposite amoxicillin-loaded membranes could be a promising fibrous-based antibiotic carrier system for dental and tissue engineering applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 966-976, 2017.


Subject(s)
Amoxicillin , Dental Materials , Durapatite/chemistry , Nanocomposites/chemistry , Polyesters/chemistry , Amoxicillin/chemistry , Amoxicillin/pharmacokinetics , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/pharmacokinetics , Dental Materials/chemistry , Dental Materials/pharmacokinetics , Humans
15.
Mater Sci Eng C Mater Biol Appl ; 75: 1115-1127, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-28415397

ABSTRACT

The replacement of small-diameter vessels is one of the main challenges in tissue engineering. Moreover, the surface modification of small-diameter vascular grafts (SDVG) is a key factor in the success of the therapy due to their increased thrombogenicity and infection susceptibility caused by the lack of a functional endothelium. In this work, electrospun scaffolds were prepared from blends of poly(L-lactic acid) (PLLA) and segmented polyurethane (PHD) with a composition designed to perform as SDVG inner layer. The scaffolds were then successfully surface-modified with heparin following two different strategies that rely on grafting of heparin to either PLLA or PHD functional groups. Both strategies afforded high heparin density, being higher for urethane methodology. The functionalized scaffolds did not cause hemolysis and inhibited platelet adhesion to a large extent. However, lysozyme/heparin-functionalized scaffolds obtained through urethane methodology achieved the highest platelet attachment inhibition. The increase in hydrophilicity and water absorption of the surface-functionalized nanostructures favored adhesion and proliferation of human adipose-derived stem cells. Heparinized surfaces conjugated with lysozyme presented microbial hydrolysis activity dependent on heparin content. Overall, a better performance obtained for urethane-modified scaffold, added to the fact that no chain scission is involved in urethane methodology, makes the latter the best choice for surface modification of PLLA/PHD 50/50 electrospun scaffolds. Scaffolds functionalized by this route may perform as advanced components of SDVG suitable for vascular tissue engineering, exhibiting biomimetic behavior, avoiding thrombi formation and providing antimicrobial features.


Subject(s)
Absorbable Implants , Blood Platelets/metabolism , Blood Vessel Prosthesis , Coated Materials, Biocompatible/chemistry , Platelet Adhesiveness , Tissue Scaffolds/chemistry , Heparin/chemistry , Humans , Muramidase/chemistry , Polyesters/chemistry , Polyurethanes/chemistry
16.
J Biomed Mater Res A ; 76(4): 729-36, 2006 Mar 15.
Article in English | MEDLINE | ID: mdl-16317720

ABSTRACT

Bioresorbable linear poly(ester-ether urethane)s with different hydrophilic character were synthesized from block copolymers of poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) (PCL-PEO-PCL) as macrodiols, and L-lysine diisocyanate (LDI). A series of PCL-PEO-PCL triblock copolymers with different PEO and PCL chain length was obtained by reacting PEO with epsilon-caprolactone. Polyurethanes were synthesized by reacting the triblock copolymers with LDI in solution using stannous 2-ethylhexanoate as catalyst. The prepared triblock copolymers and polyurethanes were fully characterized by proton nuclear magnetic resonance spectroscopy, size exclusion chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Water uptake, hydrolytic stability, and tensile properties of polyurethanes with different composition were evaluated and discussed in terms of the chain length and molecular weight of the polymers and its block components. Water uptake seems to depend on the ethylene oxide unit content of the polyurethane regardless of the triblock structure. Mechanical properties of the synthesized polymers were strongly affected by the molecular weight achieved during polymerization. The use of triblock macrodiols with different hydrophilicity allowed the preparation of a series of polyurethanes having a broad range of properties.


Subject(s)
Biocompatible Materials , Isocyanates/chemistry , Lysine/analogs & derivatives , Polymers/chemistry , Polyurethanes/chemistry , Hydrolysis , Lysine/chemistry , Materials Testing , X-Ray Diffraction
17.
Acta Biomater ; 2(6): 641-50, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16876492

ABSTRACT

The effect of gamma-radiation doses of 12.5-380 kGy on the infrared spectra, gel content, mechanical properties, and the release of oxobutyl-5-fluoro-2'-deoxyuridine (OfdUrd, an antitumor agent) from poly(ethylene-co-vinyl acetate) (EVA) films was studied. The results showed that the application of radiation doses produced a crosslinking reaction leading to a maximum gel content of about 85% in the case of 150 kGy. Higher doses did not increase the gel content in EVA films. The mechanical properties (tensile strength, percentage elongation at break and Young's modulus) of all studied EVA matrices were affected by the exposure to gamma-radiation. Irradiation doses over 50 kGy caused an increase in the Young's modulus of EVA and at the same time a decrease in the strain per cent. Moreover, the network structure formed after irradiation reduced significantly the OFdUrd release from EVA films. In this manner, the radiation dose applied to the polymeric matrix modulated the release of OFdUrd, avoiding the high concentrations that may cause severe systemic toxicity. The loading of OFdUrd to EVA film triggered a slight hyperemia after implantation, while the inflammatory reaction was only observed during the first two days.


Subject(s)
Delayed-Action Preparations/chemistry , Drug Carriers/chemistry , Membranes, Artificial , Polyvinyls/chemistry , Uridine/analogs & derivatives , Animals , Cross-Linking Reagents/chemistry , Cross-Linking Reagents/radiation effects , Diffusion , Elasticity/radiation effects , Gamma Rays , Materials Testing , Polyvinyls/radiation effects , Rats , Rats, Wistar , Uridine/administration & dosage , Uridine/chemistry
18.
Colloids Surf B Biointerfaces ; 143: 168-176, 2016 Jul 01.
Article in English | MEDLINE | ID: mdl-27003467

ABSTRACT

Levofloxacin (LV) is a hydrophilic broad-spectrum antibiotic commonly used in pulmonary treatment against recurrent infections of Pseudomonas aeruginosa, and particularly in cystic fibrosis (CF) disease. In order to study feasible carriers for LV, solid lipid nanoparticles (SLN) of myristyl myristate were prepared by the ultrasonication method in the presence of Pluronic(®)F68 under different experimental conditions and characterized by dynamic light scattering, optical, transmission and scanning electron microscopy for size and morphology. Alternatively, nanostructured lipid carriers (NLCs) were developed to improve LV encapsulation and storage. SLN showed 20.1±1.4% LV encapsulation efficiency, while the NLCs encapsulated 55.9±1.6% LV. NLC formulation exhibited a more controlled release profile than SLN formulation, but both showed a biphasic drug release pattern with burst release at the first 5h and prolonged release afterwards, demonstrated by in vitro tests. The hydrodynamic average diameter and zeta potential of NLC were 182.6±3.2nm and -10.2±0.2mV, respectively, and were stable for at least 3 months. Additionally, DNase type I was incorporated into the formulations as a "smart" component, since the enzyme could help to decrease the viscoelasticity found in the lungs of CF patients and improves the antibiotic diffusion. FTIR, XRD, DSC, TGA and nitrogen adsorption isotherms of the nanoparticles indicate the presence of the loads in a noncrystalline state. The developed formulation showed an active antimicrobial activity against P. aeruginosa and even against other opportunistic pathogens such as Staphylococcus aureus. The presence of LV-loaded NLCs reduced the formation of a bacterial biofilm, which highlighted the significance of the nanodevice as a new alternative for CF treatment.


Subject(s)
Drug Delivery Systems/methods , Levofloxacin/administration & dosage , Lipids/chemistry , Nanoparticles/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Calorimetry, Differential Scanning , Cystic Fibrosis/drug therapy , Cystic Fibrosis/metabolism , Cystic Fibrosis/microbiology , Deoxyribonucleases/chemistry , Drug Carriers/chemistry , Drug Compounding/methods , Drug Liberation , Humans , Levofloxacin/chemistry , Levofloxacin/pharmacology , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Particle Size , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
19.
Int J Pharm ; 513(1-2): 518-527, 2016 Nov 20.
Article in English | MEDLINE | ID: mdl-27667755

ABSTRACT

Electrospun mats containing cyclodextrin polymers (poly-αCD or poly-ßCD) were developed to act as wound dressings showing tunable release rate of the antifungal agent fluconazole incorporated forming inclusion complexes. Poly-αCD and poly-ßCD were prepared via cross-linking with epichlorohydrin (EPI) as water-soluble large molecular weight polymers. Then, polyCDs forming complexes with fluconazole were mixed with poly-(ε-caprolactone) (PCL) or poly(N-vinylpyrrolidone) (PVP) for electrospinning. Obtained bead-free fibers showed a random distribution, diameters in the 350-850nm range, and a variety of physical stability behaviors in aqueous environment. Mats were coated by hexamethyldisiloxane (HMDSO) plasma polymerization to create a hydrophobic layer that prevented rapid drug diffusion. HMDSO coating was evidenced by the Si content of mat surface (EDX analysis) and by the increase in the water contact angle (up to 130°). In physiological-mimicking medium, non-treated mats showed burst release of fluconazole, whereas HMDSO-coated mats sustained the release and delayed disintegration of PVP-based mats. Antifungal tests evidenced that both coated and non-coated mats efficiently inhibited the growth of Candida albicans.


Subject(s)
Antifungal Agents/chemistry , Bandages , Cellulose/chemistry , Cyclodextrins/chemistry , Drug Carriers/chemistry , Fluconazole/chemistry , Siloxanes/chemistry , Antifungal Agents/administration & dosage , Candida albicans/drug effects , Candida albicans/growth & development , Cellulose/administration & dosage , Cyclodextrins/administration & dosage , Drug Carriers/administration & dosage , Drug Liberation , Fluconazole/administration & dosage , Hydrophobic and Hydrophilic Interactions , Pyrrolidinones/administration & dosage , Pyrrolidinones/chemistry , Siloxanes/administration & dosage , Technology, Pharmaceutical
20.
J Mech Behav Biomed Mater ; 60: 220-233, 2016 07.
Article in English | MEDLINE | ID: mdl-26872337

ABSTRACT

To these days, the production of a small diameter vascular graft (<6mm) with an appropriate and permanent response is still challenging. The mismatch in the grafts mechanical properties is one of the principal causes of failure, therefore their complete mechanical characterization is fundamental. In this work the mechanical response of electrospun bilayered small-diameter vascular grafts made of two different bioresorbable synthetic polymers, segmented poly(ester urethane) and poly(L-lactic acid), that mimic the biomechanical characteristics of elastin and collagen is investigated. A J-shaped response when subjected to internal pressure was observed as a cause of the nanofibrous layered structure, and the materials used. Compliance values were in the order of natural coronary arteries and very close to the bypass gold standard-saphenous vein. The suture retention strength and burst pressure values were also in the range of natural vessels. Therefore, the bilayered vascular grafts presented here are very promising for future application as small-diameter vessel replacements.


Subject(s)
Biomimetics , Blood Vessel Prosthesis , Nanofibers , Vascular Grafting , Mechanical Phenomena , Polyesters , Polyurethanes
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