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OBJECTIVE: Skin adhesives offer many advantages over traditional wound-closure devices. Recently, the current research group reported on tissue adhesives composed of natural polymers (gelatin and alginate), which are biocompatible with mechanical properties suitable for tissue adhesion. The objective of the present study was to conduct clinical and histologic assessment of this hemostatic bioadhesive in the healing of long skin incisions (≥4 cm) in comparison with traditional and commercially available methods. METHODS: Researchers created 24 long incisions on the ventral side of two domestic pigs to compare four different treatment modalities: two topical bioadhesives based on gelatin and alginate combined with the hemostatic agent kaolin, nylon sutures, and commercial tissue adhesive N-butyl-2-cyanoacrylate. The bioadhesive compounds were spread on the incision surface and then mixed either manually or with a double-headed syringe. After 14 days, clinical and histologic measurements were performed to evaluate the healing phase of the wounds. RESULTS: The bioadhesive formulation that contained a relatively low crosslinker concentration demonstrated superior results to the formulation that contained a standard crosslinker concentration. However, no significant statistical differences were observed compared with the control incisions (sutures and commercial adhesive N-butyl-2-cyanoacrylate). This was verified by immunohistochemical analysis for epithelial integrity and scar formation as well as by clinical assessment. CONCLUSIONS: This newly developed bioadhesive demonstrated suitable properties for the closure of long incisions in a porcine skin model.
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Embucrilato , Hemostáticos , Ferida Cirúrgica , Adesivos Teciduais , Suínos , Animais , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Adesivos Teciduais/farmacologia , Adesivos Teciduais/uso terapêutico , Gelatina , AlginatosRESUMO
The development of hydrogels for maxillofacial bone regeneration holds vast potential. However, some challenges need to be addressed to further their application in clinical settings. One challenge is optimizing cell viability. To improve mechanical strength, various materials have been investigated; however, incorporation of these materials within the hydrogel network may affect cell viability. The purpose of this study was to evaluate the cell viability of novel gelatin-alginate composite hydrogels loaded with hydroxyapatite (HA) and nano-hydroxyapatite (n-HA) for maxillofacial bone regeneration. Nine different hydrogels were prepared: three loaded with 0.5%, 1%, and 3% w/v HA; three loaded with 0.25%, 0.5%, and 1% w/v n-HA; one not loaded as a control and two HA and n-HA hydrogels with a lower concentration of the EDC crosslinker. Cell viability of human osteoblasts exposed to the hydrogels as affected by the HA type, size, and concentration, as well as to the crosslinker concentration, was investigated. An Alamar Blue assay was used to evaluate cell viability in the presence of hydrogel extracts and in aqueous solutions (without the hydrogel). A qualitative model was developed for explaining cell viability and growth. Higher percentages of cell viability were observed in the hydrogels loaded with hydroxyapatite as compared with the control. The effect of HA-related parameters, i.e., particle size and concentration, was found to increase the cytotoxic effect, as expressed in lower cell viability. The most favorable composites were the n-HA hydrogels. The incorporation of n-HA in the hydrogel to form a composite seems to be a very promising approach for maxillofacial bone regeneration applications.
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Durapatita , Hidrogéis , Regeneração Óssea , Osso e Ossos , Sobrevivência Celular , Durapatita/farmacologia , Humanos , Hidrogéis/farmacologiaRESUMO
BACKGROUND: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative. OBJECTIVES: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold). METHODS: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant. RESULTS: The authors' novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days. CONCLUSIONS: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.
Assuntos
Hidrogéis/uso terapêutico , Pneumopatias/terapia , Engenharia Tecidual/métodos , Alicerces Teciduais , Alginatos , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/uso terapêutico , Catéteres , Fibroblastos , Gelatina , Humanos , Hidrogéis/administração & dosagem , Injeções , Pulmão , CamundongosRESUMO
The need for a long-term solution for filling the defects created during partial mastectomies due to breast cancer diagnosis has not been met to date. All available defect-filling methods are non-permanent and necessitate repeat procedures. Here, we report on novel injectable porous hydrogel structures based on the natural polymers gelatin and alginate, which are designed to serve for breast reconstruction and regeneration following partial mastectomy. The effects of the formulation parameters on the mechanical and physical properties were thoroughly studied. The modulus in compression and tension were in the range of native breast tissue. Both increased with the increase in the crosslinker concentration and the polymer-air ratio. Resilience was very high, above 93% for most studied formulations, allowing the scaffold to be continuously deformed without changing its shape. The combination of high resilience and low elastic modulus is favored for adipose tissue regeneration. The physical properties of gelation time and water uptake are controllable and are affected mainly by the alginate and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) concentrations and less by the polymer-air ratio. In vitro cell viability tests were performed on mouse preadipocytes and indicated high biocompatibility. The minimally invasive nature of this approach, along with the excellent properties of the scaffold, will enable the filling of complex voids while simultaneously decreasing surgical costs and greatly improving patient well-being.
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Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications.
Assuntos
Alginatos , Celulose , Hemostáticos , Hidrogéis , Caulim , Teste de Materiais , Resistência à Tração , Adesivos Teciduais , Celulose/química , Celulose/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Alginatos/química , Caulim/química , Caulim/farmacologia , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Módulo de Elasticidade , Viscosidade , Animais , Gelatina/química , Camundongos , Sobrevivência Celular/efeitos dos fármacosRESUMO
We achieved continuous, noncontact wide-field imaging and characterization of drug release from a polymeric device in vitro by uniquely using off-axis interferometric imaging. Unlike the current gold-standard methods in this field, which are usually based on chromatography and spectroscopy, our method requires no user intervention during the experiment and involves less lab consumable instruments. Using a simplified interferometric imaging system, we experimentally demonstrate the characterization of anesthetic drug release (Bupivacaine) from a soy-based protein matrix, which is used as a skin substitute for wound dressing. Our results demonstrate the potential of interferometric imaging as an inexpensive and easy-to-use alternative for characterization of drug release in vitro.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Luz , Pele Artificial , Interferometria , Fatores de TempoRESUMO
Infection of the periodontal pocket presents two major challenges for drug delivery: administration into the periodontal pocket and a high fluid clearance rate in the pocket. The current study aimed to develop and study a novel hydrogel system for delivery of the antibiotic drug metronidazole directly into the periodontal pocket via injection followed by in situ gelation. The natural polymers gelatin and alginate served as basic materials, and their crosslinking using a carbodiimide resulted in a dual hydrogel network. The study focused on the effects of the hydrogel's formulation parameters on the drug release profile and the hydrogel's physical and mechanical properties. A cell viability test was conducted on human fibroblasts. The metronidazole-loaded hydrogels demonstrated a decreasing release rate with time, where most of the drug eluted within 24 h. These hydrogels exhibited fibroblast viability of at least 75% after 24 and 48 h, indicating that they are highly biocompatible. Although the alginate concentration used in this study was relatively low, it had a strong effect on the physical as well as the mechanical properties of the hydrogel. An increase in the alginate concentration increased the crosslinking rate and enabled enhanced entanglement of the 3D structure, resulting in a decrease in the gelation time (less than 10 s) and swelling degree, which are both desired for the studied periodontal application. Increasing the gelatin concentration without changing the crosslinker concentration resulted in significant changes in the physical properties and slight changes in the mechanical properties. Metronidazole incorporation slightly decreased the hydrophilicity of the hydrogel and therefore also its viscosity, and affected the sealing ability and the tensile and compression moduli. The developed hydrogels exhibited controllable mechanical and physical properties, can target a wide range of conditions, and are therefore of high significance in the field of periodontal treatment.
Assuntos
Alginatos , Gelatina , Alginatos/química , Gelatina/química , Humanos , Hidrogéis/química , Metronidazol , Bolsa PeriodontalRESUMO
With the advent of the 5G era and the rise of the Internet of Things, various sensors have received unprecedented attention, especially wearable and stretchable sensors in the healthcare field. Here, a stretchable, self-healable, self-adhesive, and room-temperature oxygen sensor with excellent repeatability, a full concentration detection range (0-100%), low theoretical limit of detection (5.7 ppm), high sensitivity (0.2%/ppm), good linearity, excellent temperature, and humidity tolerances is fabricated by using polyacrylamide-chitosan (PAM-CS) double network (DN) organohydrogel as a novel transducing material. The PAM-CS DN organohydrogel is transformed from the PAM-CS composite hydrogel using a facile soaking and solvent replacement strategy. Compared with the pristine hydrogel, the DN organohydrogel displays greatly enhanced mechanical strength, moisture retention, freezing resistance, and sensitivity to oxygen. Notably, applying the tensile strain improves both the sensitivity and response speed of the organohydrogel-based oxygen sensor. Furthermore, the response to the same concentration of oxygen before and after self-healing is basically the same. Importantly, we propose an electrochemical reaction mechanism to explain the positive current shift of the oxygen sensor and corroborate this sensing mechanism through rationally designed experiments. The organohydrogel oxygen sensor is used to monitor human respiration in real-time, verifying the feasibility of its practical application. This work provides ideas for fabricating more stretchable, self-healable, self-adhesive, and high-performance gas sensors using ion-conducting organohydrogels.
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Dealing with wound related pain is an integral part of treatment. Systemic administration of analgesic and anesthetic agents is a common solution for providing pain relief to patients but comes at a risk of severe side effects as well as addiction. To overcome these issues, research efforts were madeto provide a platform for local controlled release of pain killers. We have developed a bilayer soy protein-based wound dressing for the controlled local release of bupivacaine to the wound site. The combination of a dense and a porous layer provides a platform for cell growth and proliferation as well as physical protection to the wound site. The current study focuses on the in vitro bupivacaine release profile from the dressing and the corresponding in vivo results of pain levels in a second-degree burn model on rats. The Rat Grimace Scale method and the Von Frey filaments method were used to quantify both, spontaneous pain and mechanically induced pain. A high burst release of 61.8 ± 1.9% of the loaded drug was obtained during the initial hour, followed by a slower release rate during the following day. The animal trials show that the RGS scores of the bupivacaine-treated group were significantly lower than these of the untreated group, proving a decrease of 51-68% in pain levels during days 1-3 after burn. Hence, successful pain reduction of spontaneous pain as well as mechanically induced pain, for at least three days after burn was achieved. It is concluded that our novel bupivacaine eluting soy protein wound dressings are a promising new concept in the field of local controlled drug release for pain management.
Assuntos
Queimaduras , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Animais , Bandagens , Bupivacaína/uso terapêutico , Queimaduras/tratamento farmacológico , Preparações de Ação Retardada/uso terapêutico , Humanos , Dor/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Ratos , Proteínas de Soja/farmacologia , Proteínas de Soja/uso terapêuticoRESUMO
Burn pain is known to be excruciating, and while burn care has greatly advanced, treatment for burn-related pain is lacking. Current pain relief methods include systemic administration of analgesics, which does not provide high drug concentration at the wound site. In the present study, soy protein was used as the base material for bupivacaine-loaded hybrid wound dressings. The effect of the formulation on the drug release profile was studied using high performance liquid chromatography, and the cytotoxicity was tested on human fibroblasts. A second-degree burn model in rats was used to quantify the efficacy of the wound dressings in vivo, using the Rat Grimace Scale. All tested films exhibited high biocompatibility, and the drug release profiles showed rapid release during the initial 5 hr and a continuous slower release for another 24 hr. Significant pain relief was achieved in the animal trials, proving a decrease of 51-68% in pain levels during days 1-3 post-burn. Hence, the results indicate a safe and controlled bupivacaine release for a period of more than 24 hr, effectively treating pain caused by second-degree burns. The understanding of the formulation-properties effects, together with our in vivo study, enables to advance this field toward tailorable systems with high therapeutic potential.
Assuntos
Bupivacaína/uso terapêutico , Dor/tratamento farmacológico , Proteínas de Soja/química , Animais , Bupivacaína/farmacologia , Queimaduras/tratamento farmacológico , Queimaduras/patologia , Morte Celular/efeitos dos fármacos , Preparações de Ação Retardada/uso terapêutico , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Masculino , Ratos WistarRESUMO
Polymers derived from natural sources are of interest in the scientific and medical communities, especially soy protein which exhibits low immunogenicity and good mechanical properties, and supports cell proliferation. Soy protein is cost-effective compared to other natural polymers and is attractive also due to its non-animal origin and relatively long storage stability. In the current study, hybrid film structures were developed and studied as a novel wound dressing platform with controlled release of three bioactive agents. The dense top layer is designed to provide mechanical support, control the water vapor permeability and to elute the antibiotic drug cloxacillin and the analgesic drug bupivacaine to the wound site. The porous sub-layer is designed to absorb the wound exudates and release the hemostatic agent tranexamic acid for bleeding control. The results show that the formulation parameters, i.e. crosslinker and plasticizer concentrations, affected the mechanical properties of the wound dressings as well as relevant physical properties (water vapor transmission rate and swelling kinetics), but had almost no effect on the drug-release profiles. While the antibiotic drug and the analgesic drug were released within several hours, the hemostatic agent was released within several minutes, according to the well designed hybrid structure. In conclusion, our novel soy protein hybrid wound dressings are biocompatible, can deliver various drugs simultaneously in a controlled fashion for each drug individually, and can be adjusted to suit various types of wounds by altering their properties through formulation effects.
Assuntos
Bandagens , Proteínas de Soja/química , Cicatrização , Analgésicos/química , Analgésicos/farmacocinética , Antibacterianos/química , Antibacterianos/farmacocinética , Materiais Biocompatíveis/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Hemostáticos/química , Hemostáticos/farmacocinética , Humanos , Teste de Materiais , Polímeros/química , Polímeros/farmacocinética , Porosidade , Cicatrização/efeitos dos fármacosRESUMO
Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7-15% for fibroblasts and 6-8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules.
Assuntos
Dextranos/química , Sistemas de Liberação de Medicamentos , Fibrina/química , Fluoresceína-5-Isotiocianato/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Compostos Heterocíclicos de 4 ou mais Anéis/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/química , Camundongos , Modelos Teóricos , Células NIH 3T3 , Regeneração , Medicina Regenerativa/métodos , Engenharia Tecidual/métodosRESUMO
Drug-eluting medical implants are actually active implants that induce healing effects, in addition to their regular task of support. This effect is achieved by controlled release of active pharmaceutical ingredients (API) into the surrounding tissue. In this chapter we focus on three types of drug-eluting devices: drug-eluting vascular stents, drug-eluting wound dressings and protein-eluting scaffolds for tissue regeneration, thus describing both internal and external implants. Each of these drug-eluting devices also presents an approach for solving the drug release issue. Most drug-eluting vascular stents are loaded with water-insoluble antiproliferative agents, and their diffusion from the device to the surrounding tissue is relatively slow. In contrast, most drug-eluting wound dressings are loaded with highly water-soluble antibacterial agents and the issue of fast release must therefore be addressed. Growth factor release from scaffolds for tissue regeneration offers a new approach of incorporating high-molecular-weight bioactive agents which are very sensitive to process conditions and preserve their activity during the preparation stage. The drug-eluting medical implants are described here in terms of matrix formats and polymers, incorporated drugs and their release profiles from the implants, and implant functioning. Basic elements, such as new composite core/shell fibers and structured films, can be used to build new antibiotic-eluting devices. As presented in this chapter, the effect of the processing parameters on the microstructure and the resulting drug release profiles, mechanical and physical properties, and other relevant properties, must be elucidated in order to achieve the desired properties. Newly developed implants and novel modifications of previously developed approaches have enhanced the tools available for creating clinically important biomedical applications.
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Sistemas de Liberação de Medicamentos , Stents Farmacológicos , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Bandagens , Reestenose Coronária/prevenção & controle , Humanos , Polímeros/química , Alicerces Teciduais , Ferimentos e Lesões/tratamento farmacológicoRESUMO
Wound dressings aim to restore the milieu required for skin regeneration by protecting the wound from environmental threats, including penetration of bacteria, and by maintaining a moist healing environment. A wide variety of wound dressing products targeting various types of wounds and different aspects of the wound healing process are currently available on the market. Ideally, a dressing should be easy to apply and remove, and its design should meet both physical and mechanical requirements; namely water absorbance and transmission rate, handleability and strength. In this article, our novel biodegradable antibiotic-eluting wound dressings are described and the engineering aspects in the design are emphasized. These unique new wound dressings are based on a polyglyconate mesh, coated with a porous Poly(dl-lactic-co-glycolic acid) matrix. They demonstrated excellent mechanical and physical properties and desired release profiles of antibiotic drugs which enable bacterial inhibition. Hence, a new generation of wound dressings is now emerging with clear benefits. These include better protection against infection and reducing the need for frequent dressing changing.
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Curativos Oclusivos , Ferimentos e Lesões/terapia , Antibacterianos/administração & dosagem , Ceftazidima/administração & dosagem , Preparações de Ação Retardada , Desenho de Equipamento , Feminino , Humanos , Teste de Materiais , Fenômenos Mecânicos , PolímerosRESUMO
BACKGROUND: Periodontal disease is infectious in nature and leads to an inflammatory response. It arises from the accumulation of subgingival bacterial plaque and leads to the loss of attachment, increased probing depth, and bone loss. It is one of the world's most prevalent chronic diseases. In this study we developed and studied metronidazole-loaded 50/50 poly(DL-lactide-co-glycolide) (PDLGA), 75/25 PDLGA, and poly(DL-lactic acid) (PDLLA) films. These films are designed to be inserted into the periodontal pocket and treat infections with controlled-release metronidazole for >or=1 month. METHODS: The structured films were prepared using the solution-casting technique. Concentrated solutions and high solvent-evaporation rates were used to get most of the drug located in the bulk, i.e., in whole film's volume. The effects of copolymer composition and drug content on the release profile, cell growth, and bacterial inhibition were investigated. RESULTS: The PDLLA and 75/25 PDLGA films generally exhibited a low- or medium-burst release followed by a moderate release at an approximately constant rate, whereas the 50/50 PDLGA films exhibited a biphasic release profile. The drug released from films loaded with 10% weight/weight metronidazole resulted in a significant decrease in bacterial viability within several days. When exposed to human gingival fibroblasts in cell culture conditions, these films maintained their normal fibroblastic features. CONCLUSIONS: This study enabled the understanding of metronidazole-release kinetics from bioabsorbable polymeric films. The developed systems demonstrated good biocompatibility and the ability to inhibit Bacteroides fragilis growth; therefore, they may be useful in the treatment of periodontal diseases.
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Anti-Infecciosos Locais/administração & dosagem , Bacteroides fragilis/efeitos dos fármacos , Implantes de Medicamento , Metronidazol/administração & dosagem , Bolsa Periodontal/tratamento farmacológico , Implantes Absorvíveis , Infecções por Bacteroides/tratamento farmacológico , Células Cultivadas , Implantes de Medicamento/síntese química , Implantes de Medicamento/toxicidade , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Humanos , Teste de Materiais , Testes de Sensibilidade Microbiana , Bolsa Periodontal/microbiologia , Poliésteres/síntese química , Poliésteres/toxicidade , Poliglactina 910/síntese química , Poliglactina 910/toxicidadeRESUMO
New core/shell fiber structures loaded with paclitaxel were developed and studied. These composite fibers are ideal for forming thin, delicate, biomedically important structures for various applications. Possible applications include fiber-based endovascular stents that mechanically support blood vessels while delivering drugs for preventing restenosis directly to the blood vesel wall, or drug delivery systems for treatment of cancer. The core/shell fiber structures were formed by "coating" dense core fibers with porous paclitaxel-containing poly(DL-lactic-co-glycolic acid) (PDLGA) structures. Shell preparation ("coating") was performed by freeze-drying water in oil emulsions. The present study focused on the effects of the emulsion's formulation (composition) and processing conditions on the paclitaxel release profile and on the fibers' tensile mechanical properties. In general, the porous PDLGA shell released approximately 40% of the paclitaxel, with most of the release occurring during the first 30 days. The main release mechanism during the tested period is diffusion, rather than polymer degradation. The release rate and quantity increased with increased drug content or decreased polymer content, whereas the organic:aqueous phase ratio had practically no effect on the release profile. These new composite fibers are strong and flexible enough to be used as basic elements for stents. We demonstrated that proper selection of processing conditions based on kinetic and thermodynamic considerations can yield polymer/drug systems with the desired drug release behavior and good mechanical properties.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Antineoplásicos Fitogênicos/análise , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Emulsões , Liofilização , Microscopia Eletrônica de Varredura , Nylons , Paclitaxel/análise , Porosidade , Solubilidade , Propriedades de Superfície , Tensoativos , Resistência à TraçãoRESUMO
Poly(DL-lactic-co-glycolic acid) microspheres are prepared using a double-emulsion technique and are loaded with the model enzyme horseradish peroxidase (HRP). These microspheres can be used alone or as coatings for bioresorbable fibers that may be used as scaffolds for tissue regeneration applications. The present study focuses on the effect of the copolymer's composition and initial molecular weight on the microsphere structure, encapsulation efficiency, and cumulative protein release for 12 weeks. The release profiles generally exhibits an initial burst effect accompanied by slow release over an extended period of time, during which diffusion rather than degradation controlled HRP release from these structures. An increase in the initial molecular weight or in the copolymer's lactic acid content results in larger microspheres with smoother surfaces, and a decrease in the burst release and in the total HRP release. Molecular weight is found to have a stronger effect than copolymer composition. We demonstrate that it is possible to obtain versatile release profiles, which can be tailored for specific applications by choosing the right initial molecular weight and copolymer composition.
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Peroxidase do Rábano Silvestre/química , Polímeros/química , Materiais Biocompatíveis , Microscopia Eletrônica de Varredura , Microesferas , Peso MolecularRESUMO
A mathematical model for predicting bioactive agent release profiles from core/shell fiber structures was developed and studied. These new composite fibers, which combine good mechanical properties with desired protein release profiles, are designed for use in tissue regeneration and other biomedical applications. These fibers are composed of an inner dense polymeric core surrounded by a porous bioresorbable shell, which encapsulates the bioactive agent molecules. The model is based on Fick's second law of diffusion, and on two major assumptions: (a) first-order degradation kinetics of the porous shell, and (b) a nonconstant diffusion coefficient for the bioactive agent, which increases with time because of degradation of the host polymer. Three factors are evaluated and included in this model: a porosity factor, a tortuosity factor, and a polymer concentration factor. Our study indicates that the model correlates well with in vitro release results, exhibiting a mean error of less than 2.2% for most studied cases. In this study, the model was used for predicting protein release profiles from fibers with shells of various initial molecular weights and for predicting the release of proteins with various molecular weights. This new model exhibits a potential for simulating fibrous systems for a wide variety of biomedical applications.
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Resinas Compostas/farmacocinética , Preparações de Ação Retardada/farmacocinética , Modelos Teóricos , Materiais Biocompatíveis , Difusão , Composição de Medicamentos , PorosidadeRESUMO
New core/shell fiber structures loaded with paclitaxel were developed and studied. These composite fibers are ideal for forming thin, delicate, biomedically important structures for various applications. Possible applications include fiber-based endovascular stents that mechanically support blood vessels while delivering drugs for preventing restenosis directly to the blood vessel wall, or drug delivery systems for cancer treatment. The core/shell fiber structures were formed by "coating" nylon fibers with porous paclitaxel-containing poly(DL-lactic-co-glycolic acid) structures. Shell preparation ("coating") was performed by freeze-drying water in oil emulsions. The present study focused on the effects of the emulsion's formulation (composition) and processing conditions on the porous shell structure, which actually reflects the emulsion's stability and also the drug release profile from the fibers. In general, extremely porous "shell" structures were obtained with good adhesion to the core fiber. An increase in the emulsion's drug content and copolymer composition demonstrated a significant effect on pore size and distribution, because of enhanced emulsion instability, whereas the homogenization rate and duration had only a slight effect on the pores' microstructure. The thermodynamic parameters in the studied system are thus more important than the kinetic parameters in determining the emulsion's stability and the shell's porous structure.
Assuntos
Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Paclitaxel/administração & dosagem , Preparações de Ação Retardada , Estabilidade de Medicamentos , Emulsões , Humanos , Técnicas In Vitro , Ácido Láctico/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Paclitaxel/farmacocinética , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Propriedades de Superfície , TermodinâmicaRESUMO
Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections. Poly(L-lactic acid) and poly (D,L-lactic-co-glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration. Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.