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1.
Biomolecules ; 14(3)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38540779

RESUMO

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14-1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.


Assuntos
Matricaria , Óleos Voláteis , Animais , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida , Espectrometria de Massas em Tandem , Analgésicos/farmacologia , Analgésicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Óleos Voláteis/farmacologia , Etanol , Fenóis/farmacologia , Antioxidantes/química
2.
Sci Rep ; 14(1): 6883, 2024 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519558

RESUMO

We developed a reporter system based on simultaneous expression of two fluorescent proteins: GFP as a reporter of the capacity of protein synthesis and mutated mScarlet-I as a reporter of translational errors. Because of the unique stop codons or frameshift mutations introduced into the mScarlet-I gene, red fluorescence was produced only after a mistranslation event. These reporters allowed us to estimate mistranslation at a single cell level using either flow cytometry or fluorescence microscopy. We found that laboratory strains of Escherichia coli are more prone to mistranslation compared to the clinical isolates. As relevant for uropathogenic E. coli, growth in human urine elevated translational frameshifting compared to standard laboratory media, whereas different standard media had a small effect on translational fidelity. Antibiotic-induced mistranslation was studied by using amikacin (aminoglycoside family) and azithromycin (macrolide family). Bactericidal amikacin induced preferably stop-codon readthrough at a moderate level. Bacteriostatic azithromycin on the other hand induced both frameshifting and stop-codon readthrough at much higher level. Single cell analysis revealed that fluorescent reporter-protein signal can be lost due to leakage from a fraction of bacteria in the presence of antibiotics, demonstrating the complexity of the antimicrobial activity.


Assuntos
Antibacterianos , Mutação da Fase de Leitura , Humanos , Antibacterianos/farmacologia , Azitromicina/farmacologia , Amicacina , Escherichia coli/genética , Códon de Terminação/genética , Biossíntese de Proteínas
3.
Plants (Basel) ; 13(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38337883

RESUMO

Galenic preparations of German chamomile are used to treat mild skin diseases, inflammation, and spasms, and they have also been reported to have anxiolytic and sedative effects. The medicinal use of chamomile is well known in ethnomedicine. After obtaining its galenic preparations, there is lots of waste left, so it is expedient to develop waste-free technologies. The aims of this study were to gain knowledge of the ethnomedical status of chamomile in the past and present, develop methods for preparing essential oils and dry extracts from German chamomile flowers using complex processing, reveal the phytochemical composition of such extracts, and verify the analgesic and soporific activity of the extracts. Two methods for the complex processing of German chamomile flowers were developed, which allowed us to obtain the essential oil and dry extracts of the tincture and aqueous extracts as byproducts. A total of 22 phenolic compounds (7 hydroxycinnamic acids, 13 flavonoids, and 2 phenolic acids) were found in the dry extracts by using UPLC-MS/MS. In total, nine main terpenoids were identified in the chamomile oil, which is of the bisabolol chemotype. During the production of chamomile tincture, a raw material-extractant ratio of 1:14-1:16 and triple extraction are recommended for its highest yield. In in vivo studies with mice and rats, the extracts showed analgesic activity and improvements in sleep. The highest sedative and analgesic effects in rodents were found with the dry extract prepared by using a 70% aqueous ethanol solution for extraction at a dose of 50 mg/kg. The developed methods for the complex processing of German chamomile flowers are advisable for implementation into the pharmaceutical industry to reduce the volume of waste during the production of its essential oil and tincture, and to obtain new products.

4.
Biomater Sci ; 12(4): 949-963, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38221844

RESUMO

The shortage of face masks and the lack of antipathogenic functions has been significant since the recent pandemic's inception. Moreover, the disposal of an enormous number of contaminated face masks not only carries a significant environmental impact but also escalates the risk of cross-contamination. This study proposes a strategy to upgrade available surgical masks into antibacterial masks with enhanced particle and bacterial filtration. Plasmonic nanoparticles can provide photodynamic and photothermal functionalities for surgical masks. For this purpose, gold nanorods act as on-demand agents to eliminate pathogens on the surface of the masks upon near-infrared light irradiation. Additionally, the modified masks are furnished with polymer electrospun nanofibrous layers. These electrospun layers can enhance the particle and bacterial filtration efficiency, not at the cost of the pressure drop of the mask. Consequently, fabricating these prototype masks could be a practical approach to upgrading the available masks to alleviate the environmental toll of disposable face masks.


Assuntos
Nanofibras , Nanopartículas , Nanotubos , Máscaras , Filtração
5.
Eur J Pharm Sci ; 192: 106648, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37992909

RESUMO

Conventional wound infection treatments neither actively promote wound healing nor address the growing problem of antibacterial resistance. Antimicrobial peptides (AMPs) are natural defense molecules, released from host cells, which may be rapidly bactericidal, modulate host-immune responses, and/or act as endogenous mediators for wound healing. However, their routine clinical use has hitherto been hindered due to their instability in the wound environment. Here we describe an electrospun carrier system for topical application of pleurocidin, demonstrating sufficient AMP release from matrices to kill wound-associated pathogens including Acinetobacter baumannii and Pseudomonas aeruginosa. Pleurocidin can be incorporated into polyvinyl alcohol (PVA) fiber matrices, using coaxial electrospinning, without major drug loss with a peptide content of 0.7% w/w predicted sufficient to kill most wound associated species. Pleurocidin retains its activity on release from the electrospun fiber matrix and completely inhibits growth of two strains of A. baumannii (AYE; ATCC 17978) and other ESKAPE pathogens. Inhibition of P. aeruginosa strains (PAO1; NCTC 13437) is, however, matrix weight per volume dependent, with only larger/thicker matrices maintaining complete inhibition. The resulting estimation of pleurocidin release from the matrix reveals high efficiency, facilitating a greater AMP potency. Wound matrices are often applied in parallel or sequentially with the use of standard wound care with biocides, therefore the presence and effect of biocides on pleurocidin potency was tested. It was revealed that combinations displayed additive or modestly synergistic effects depending on the biocide and pathogens which should be considered during the therapy. Taken together, we show that electrospun, pleurocidin-loaded wound matrices have potential to be investigated for wound infection treatment.


Assuntos
Desinfetantes , Infecção dos Ferimentos , Humanos , Proteínas de Peixes/farmacologia , Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Desinfetantes/farmacologia , Infecção dos Ferimentos/tratamento farmacológico
6.
Mol Pharm ; 20(2): 1230-1246, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669095

RESUMO

Increasing evidence suggests that the chronicity of wounds is associated with the presence of bacterial biofilms. Therefore, novel wound care products are being developed, which can inhibit biofilm formation and/or treat already formed biofilms. A lack of standardized assays for the analysis of such novel antibacterial drug delivery systems enhances the need for appropriate tools and models for their characterization. Herein, we demonstrate that optimized and biorelevant in vitro and ex vivo wound infection and biofilm models offer a convenient approach for the testing of novel antibacterial wound dressings for their antibacterial and antibiofilm properties, allowing one to obtain qualitative and quantitative results. The in vitro model was developed using an electrospun (ES) thermally crosslinked gelatin-glucose (GEL-Glu) matrix and an ex vivo wound infection model using pig ear skin. Wound pathogens were used for colonization and biofilm development on the GEL-Glu matrix or pig skin with superficial burn wounds. The in vitro model allowed us to obtain more reproducible results compared with the ex vivo model, whereas the ex vivo model had the advantage that several pathogens preferred to form a biofilm on pig skin compared with the GEL-Glu matrix. The in vitro model functioned poorly for Staphylococcus epidermidis biofilm formation, but it worked well for Escherichia coli and Staphylococcus aureus, which were able to use the GEL-Glu matrix as a nutrient source and not only as a surface for biofilm growth. On the other hand, all tested pathogens were equally able to produce a biofilm on the surface of pig skin. The developed biofilm models enabled us to compare different ES dressings [pristine and chloramphenicol-loaded polycaprolactone (PCL) and PCL-poly(ethylene oxide) (PEO) (PCL/PEO) dressings] and understand their biofilm inhibition and treatment properties on various pathogens. Furthermore, we show that biofilms were formed on the wound surface as well as on a wound dressing, indicating that the demonstrated methods mimic well the in vivo situation. Colony forming unit (CFU) counting and live biofilm matrix as well as bacterial DNA staining together with microscopic imaging were performed for biofilm quantification and visualization, respectively. The results showed that both wound biofilm models (in vitro and ex vivo) enabled the evaluation of the desired antibiofilm properties, thus facilitating the design and development of more effective wound care products and screening of various formulations and active substances.


Assuntos
Antibacterianos , Infecção dos Ferimentos , Suínos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cloranfenicol/farmacologia , Infecção dos Ferimentos/microbiologia , Biofilmes , Bandagens
7.
Nanomaterials (Basel) ; 12(23)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36500958

RESUMO

History has demonstrated that the uncontrolled fast thriving of potentially pathogenic microorganisms may lead to serious consequences and, thus, the approaches helping to control the microbial numbers in infectional hot-spots are necessary [...].

8.
Eur J Pharm Biopharm ; 180: 48-62, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36167272

RESUMO

Despite the advances in the field of pharmaceutical materials and technology, topical administration remains a method of choice for the treatment of eye diseases such as glaucoma, with eye drops being a leading dosage form. Their main disadvantage is a very short drug residence time and thus poor drug bioavailability, leading to the necessity of continuous repeated dosing. Mucoadhesive electrospun nanofibers are promising candidates for overcoming these challenges, while still benefiting from topical ocular administration. As an alternative for eye drops, a nanofibrous drug delivery system (DDS) for the delivery of brinzolamide (BRZ), based on ß-cyclodextrin (ß-CD), hydroxypropyl cellulose (HPC) and polycaprolactone (PCL), was designed. The results showed ß-CD/BRZ guest-host interactions, successful drug incorporation into the nanofibers, and the possibility of more accurate dosing in comparison with the control eye drops. Drug permeation through sheep corneas was almost linear in time, achieving therapeutic concentrations in the receptor medium, and mucoadhesion to sheep eye mucosa was relatively high in case of formulations with high HPC content. All formulations were biocompatible, their mechanical properties were sufficient to handle them without caution and UV irradiation was suitable to reduce bioburden of the fibers matrix, yet no antibacterial properties of BRZ were observed.


Assuntos
Glaucoma , Nanofibras , Tiazinas , Ovinos , Animais , Tiazinas/uso terapêutico , Sistemas de Liberação de Medicamentos , Soluções Oftálmicas , Glaucoma/tratamento farmacológico
9.
PLoS One ; 17(6): e0268806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35687549

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of the virus is ongoing. One of the mechanisms by which neutralizing antibodies (NAbs) block virus entry into cells encompasses interaction inhibition between the cell surface receptor angiotensin-converting enzyme 2 (ACE2) and the spike (S) protein of SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in the blood of cattle. Pregnant cows produce NAbs upon immunization, and antibodies move into the colostrum immediately before calving. Here, we immunized cows with SARS-CoV-2 S1 receptor binding domain (RBD) protein in proper adjuvant solutions, followed by one boost with SARS-CoV-2 trimeric S protein and purified immunoglobulins from colostrum. We demonstrate that this preparation indeed blocks the interaction between the trimeric S protein and ACE2 in different in vitro assays. Moreover, we describe the formulation of purified immunoglobulin preparation into a nasal spray. When administered to human subjects, the formulation persisted on the nasal mucosa for at least 4 hours, as determined by a clinical study. Therefore, we are presenting a solution that shows great potential to serve as a prophylactic agent against SARS-CoV-2 infection as an additional measure to vaccination and wearing masks. Moreover, our technology allows for rapid and versatile adaptation for preparing prophylactic treatments against other diseases using the defined characteristics of antibody movement into the colostrum.


Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Bovinos , Colostro/metabolismo , Feminino , Humanos , Gravidez , Glicoproteína da Espícula de Coronavírus
10.
Antimicrob Agents Chemother ; 66(5): e0241221, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35435706

RESUMO

Azithromycin is a clinically important drug for treating invasive salmonellosis despite poor activity in laboratory assays for MIC. Addition of the main buffer in blood, bicarbonate, has been proposed for more physiologically relevant and more predictive testing conditions. However, we show here that bicarbonate-triggered lowering of azithromycin MIC is entirely due to alkalization of insufficiently buffered media. In addition, bicarbonate is unlikely to be altering efflux pump activity.


Assuntos
Anti-Infecciosos , Azitromicina , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Azitromicina/farmacologia , Bicarbonatos/farmacologia , Meios de Cultura , Testes de Sensibilidade Microbiana
11.
Pharmacol Ther ; 232: 107990, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34592202

RESUMO

Antimicrobial peptides (AMPs) are potent, mostly cationic, and amphiphilic broad-spectrum host defense antimicrobials that are produced by all organisms ranging from prokaryotes to humans. In addition to their antimicrobial actions, they modulate inflammatory and immune responses and promote wound healing. Although they have clear benefits over traditional antibiotic drugs, their wide therapeutic utilization is compromised by concerns of toxicity, stability, and production costs. Recent advances in nanotechnology have attracted increasing interest to unleash the AMPs' immense potential as broad-spectrum antibiotics and anti-biofilm agents, against which the bacteria have less chances to develop resistance. Topical application of AMPs promotes migration of keratinocytes and fibroblasts, and contributes significantly to an accelerated wound healing process. Delivery of AMPs by employing nanotechnological approaches avoids the major disadvantages of AMPs, such as instability and toxicity, and provides a controlled delivery profile together with prolonged activity. In this review, we provide an overview of the key properties of AMPs and discuss the latest developments in topical AMP therapy using nanocarriers. We use chronic hard-to-heal wounds-complicated by infections, inflammation, and stagnated healing-as an example of an unmet medical need for which the AMPs' wide range of therapeutic actions could provide the most potential benefit. The use of innovative materials and sophisticated nanotechnological approaches offering various possibilities are discussed in more depth.


Assuntos
Anti-Infecciosos , Peptídeos Antimicrobianos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Humanos , Nanotecnologia
12.
Pharmaceutics ; 13(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34834157

RESUMO

The hydration of phospholipids, electrospun into polymeric nanofibers and used as templates for liposome formation, offers pharmaceutical advantages as it avoids the storage of liposomes as aqueous dispersions. The objective of the present study was to electrospin and characterize amphiphilic nanofibers as templates for the preparation of antibiotic-loaded liposomes and compare this method with the conventional film-hydration method followed by extrusion. The comparison was based on particle size, encapsulation efficiency and drug-release behavior. Chloramphenicol (CAM) was used at different concentrations as a model antibacterial drug. Phosphatidylcoline (PC) with polyvinylpyrrolidone (PVP), using ethanol as a solvent, was found to be successful in fabricating the amphiphilic composite drug-loaded nanofibers as well as liposomes with both methods. The characterization of the nanofiber templates revealed that fiber diameter did not affect the liposome size. According to the optical microscopy results, the immediate hydration of phospholipids deposited on the amphiphilic nanofibers occurred within a few seconds, resulting in the formation of liposomes in water dispersions. The liposomes appeared to aggregate more readily in the concentrated than in the diluted solutions. The drug encapsulation efficiency for the fiber-hydrated liposomes varied between 14.9 and 28.1% and, for film-hydrated liposomes, between 22.0 and 77.1%, depending on the CAM concentrations and additional extrusion steps. The nanofiber hydration method was faster, as less steps were required for the in-situ liposome preparation than in the film-hydration method. The liposomes obtained using nanofiber hydration were smaller and more homogeneous than the conventional liposomes, but less drug was encapsulated.

13.
Sci Data ; 8(1): 192, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315906

RESUMO

Data sharing is one of the cornerstones of modern science that enables large-scale analyses and reproducibility. We evaluated data availability in research articles across nine disciplines in Nature and Science magazines and recorded corresponding authors' concerns, requests and reasons for declining data sharing. Although data sharing has improved in the last decade and particularly in recent years, data availability and willingness to share data still differ greatly among disciplines. We observed that statements of data availability upon (reasonable) request are inefficient and should not be allowed by journals. To improve data sharing at the time of manuscript acceptance, researchers should be better motivated to release their data with real benefits such as recognition, or bonus points in grant and job applications. We recommend that data management costs should be covered by funding agencies; publicly available research data ought to be included in the evaluation of applications; and surveillance of data sharing should be enforced by both academic publishers and funders. These cross-discipline survey data are available from the plutoF repository.

14.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946815

RESUMO

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.


Assuntos
Berberina/administração & dosagem , Berberina/química , Composição de Medicamentos , Lipossomos , Nanopartículas , Administração Oral , Fenômenos Químicos , Lipossomos/química , Estrutura Molecular , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Solubilidade
15.
Eur J Pharm Sci ; 158: 105619, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33115676

RESUMO

Hot-melt extruded (HME) filaments are an essential intermediate product for the three- dimensional (3D) printing of drug delivery systems (DDSs) by the fused deposition modelling (FDM) process. The aim of this study was to design novel polymeric 3D-printable HME filaments loaded with active pharmaceutical ingredients (APIs). The physical solid-state properties, mechanical properties, drug release and short-term storage stability of the filaments and 3D-printed DDSs were studied. Physical powder mixtures of polycaprolactone (PCL), plasticizer and API were manually blended, extruded by a single-screw extruder, and printed by a table-top FDM 3D-printing system. The composition of PCL and arabic gum (ARA) enabled the incorporation of 20%, 30% and 40% (w/w) of indomethacin (IND) and theophylline (THEO) into the HME filaments. The uneven distribution of API throughout the filaments impaired 3D printing. The HME filaments loaded with 20% IND or THEO were selected for the further analysis and printing tests (the ratio of PCL, ARA and IND or THEO was 7:1:2, respectively). The IND filaments were yellowish, mechanically strong and flexible, and they had a uniform filament diameter and smooth outer surface. The filaments containing THEO were smooth and off-white. The 3D-printed tablets fabricated from IND or THEO-loaded filaments showed sustained drug release in vitro. The drug release rate, however, significantly increased by changing the geometry of 3D-printed tablets from a conventional tablet structure to an unorthodox lattice ("honeycomb") structure. Overall, the combination of PCL and ARA provides an interesting novel polymeric carrier system for 3D-printable HME filaments and tablets.


Assuntos
Poliésteres , Impressão Tridimensional , Liberação Controlada de Fármacos , Comprimidos , Tecnologia Farmacêutica
16.
Chemistry ; 27(20): 6112-6130, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33284500

RESUMO

The Coronavirus disease 2019 (COVID-19) emergency has demonstrated that the utilization of face masks plays a critical role in limiting the outbreak. Healthcare professionals utilize masks all day long without replacing them very frequently, thus representing a source of cross-infection for patients and themselves. Nanotechnology is a powerful tool with the capability to produce nanomaterials with unique physicochemical and antipathogen properties. Here, how to realize non-disposable and highly comfortable respirators with light-triggered self-disinfection ability by bridging bioactive nanofiber properties and stimuli-responsive nanomaterials is outlined. The visionary road highlighted in this Concept is based on the possibility of developing a new generation of masks based on multifunctional membranes where the presence of nanoclusters and plasmonic nanoparticles arranged in a hierarchical structure enables the realization of a chemically driven and on-demand antipathogen activities. Multilayer electrospun membranes have the ability to dissipate humidity present within the mask, enhancing the wearability and usability. The photothermal disinfected membrane is the core of these 3D printed and reusable masks with moisture pump capability. Personalized face masks with smart nano-assisted destruction of pathogens will bring enormous advantages to the entire global community, especially for front-line personnel, and will open up great opportunities for innovative medical applications.


Assuntos
COVID-19 , Humanos , Máscaras , SARS-CoV-2
17.
ACS Omega ; 5(46): 30011-30022, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33251437

RESUMO

Electrospun fiber scaffolds have a huge potential for the successful treatment of infected wounds based on their unique properties. Although several studies report novel drug-loaded electrospun fiber-based biomaterials, many of these do not provide information on their interactions with eukaryotic and bacterial cells. The main aim of this study was to develop antibacterial drug-loaded porous biocompatible polycaprolactone (PCL) fiber scaffolds mimicking the native extracellular matrix for wound healing purposes. Mechanical property evaluation and different biorelevant tests were conducted in order to understand the structure-activity relationships and reveal how the surface porosity of fibers and the fiber diameter affect the scaffold interactions with the living bacterial and eukaryotic fibroblast cells. Cell migration and proliferation assays and antibiofilm assays enabled us to enlighten the biocompatibility and safety of fiber scaffolds and their suitability to be used as scaffolds for the treatment of infected wounds. Here, we report that porous PCL microfiber scaffolds obtained using electrospinning at high relative humidity served as the best surfaces for fibroblast attachment and growth compared to the nonporous microfiber or nonporous nanofiber PCL scaffolds. Porous chloramphenicol-loaded microfiber scaffolds were more elastic compared to nonporous scaffolds and had the highest antibiofilm activity. The results indicate that in addition to the fiber diameter and fiber scaffold porosity, the single-fiber surface porosity and its effect on drug release, mechanical properties, cell viability, and antibiofilm activity need to be understood when developing antibacterial biocompatible scaffolds for wound healing applications. We show that pores on single fibers within an electrospun scaffold, in addition to nano- and microscale diameter of the fibers, change the living cell-fiber interactions affecting the antibiofilm efficacy and biocompatibility of the scaffolds for the local treatment of wounds.

18.
Pharmaceutics ; 12(5)2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32443445

RESUMO

The development of biomaterials for wound healing applications requires providing a number of properties, such as antimicrobial action, facilitation of cell proliferation, biocompatibility and biodegradability. The aim of the present study was to investigate morphological and mechanical properties of zein-based microfibers, ultimately aimed at creating an environment suitable for wound healing. This was achieved through co-axial electrospinning of core-shell microfibers, with zein protein in the core and polyethylene oxide (PEO) in the shell. Small amounts of PEO or stearic acid were additionally incorporated into the fiber core to modify the morphology and mechanical properties of zein fibers. The presence of PEO in the core was found to be essential for the formation of tubular fibers, whereas PEO in the shell enhanced the stability of the microfibers in water and ensured high elasticity of the microfiber mats. Tetracycline hydrochloride was present in an amorphous form within the fibers, and displayed a burst release as a result of pore-formation in the fibers. The developed systems exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli, and showed no cytotoxic effect on fibroblasts. Biocompatibility, antimicrobial activity and favorable morphological and mechanical properties make the developed zein-based microfibers a potential biomaterial for wound healing purposes.

19.
Pharmaceutics ; 11(12)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842385

RESUMO

Polymeric wound dressings with advanced properties are highly preferred formulations to promote the tissue healing process in wound care. In this study, a combinational technique was investigated for the fabrication of bi-layered carriers from a blend of polyvinyl alcohol (PVA) and sodium alginate (SA). The bi-layered carriers were prepared by solvent casting in combination with two surface modification approaches: electrospinning or three-dimensional (3D) printing. The bi-layered carriers were characterized and evaluated in terms of physical, physicochemical, adhesive properties and for the safety and biological cell behavior. In addition, an initial inkjet printing trial for the incorporation of bioactive substances for drug delivery purposes was performed. The solvent cast (SC) film served as a robust base layer. The bi-layered carriers with electrospun nanofibers (NFs) as the surface layer showed improved physical durability and decreased adhesiveness compared to the SC film and bi-layered carriers with patterned 3D printed layer. Thus, these bi-layered carriers presented favorable properties for dermal use with minimal tissue damage. In addition, electrospun NFs on SC films (bi-layered SC/NF carrier) provided the best physical structure for the cell adhesion and proliferation as the highest cell viability was measured compared to the SC film and the carrier with patterned 3D printed layer (bi-layered SC/3D carrier). The surface properties of the bi-layered carriers with electrospun NFs showed great potential to be utilized in advanced technical approach with inkjet printing for the fabrication of bioactive wound dressings.

20.
Pharmaceutics ; 11(10)2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31569535

RESUMO

Haemanthamine (HAE) has been proven as a potential anticancer agent. However, the therapeutic use of this plant-origin alkaloid to date is limited due to the chemical instability and poorly water-soluble characteristics of the agent. To overcome these challenges, we developed novel amphiphilic electrospun nanofibers (NFs) loaded with HAE, phosphatidylcholine (PC) and polyvinylpyrrolidone (PVP), and intended for a stabilizing platform (template) of self-assembled liposomes of the active agent. The NFs were fabricated with a solvent-based electrospinning method. The chemical structure of HAE and the geometric properties, molecular interactions and physical solid-state properties of the NFs were investigated using nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC), respectively. An in-house dialysis-based dissolution method was used to investigate the drug release in vitro. The HAE-loaded fibers showed a nanoscale size ranging from 197 nm to 534 nm. The liposomes with a diameter between 63 nm and 401 nm were spontaneously formed as the NFs were exposed to water. HAE dispersed inside liposomes showed a tri-modal dissolution behavior. In conclusion, the present amphiphilic NFs loaded with HAE are an alternative approach for the formulation of a liposomal drug delivery system and stabilization of the liposomes of the present alkaloid.

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