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1.
Int J Pharm ; 554: 312-321, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30395954

RESUMO

Drug coated balloons (DCBs) have proven to be a suitable alternative for the treatment of cardiovascular diseases. They allow for uniform delivery of an antiproliferative drug to the stenotic site without permanent implantation of the device in the patient's body. There are, however, regulatory concerns regarding the lack of data associated with variable drug delivery to the target site, which can be related to the coating process. This study describes the process for an in-house micro-pipetting coating method that incorporates a laboratory-developed coating equation for determining optimal coating parameters. The coating solutions included a common drug of choice, paclitaxel, along with a hydrophilic excipient, such as iopromide. It was found that using a revolution rate of 240 rev/min, a flow rate of 25 µL/min and a translational speed of 0.033 cm/s resulted in visually uniform coatings. High performance liquid chromatography (HPLC) allowed for the determination of paclitaxel content on the balloon surface. Scanning electron microscopy (SEM) enabled analysis of coating thickness and texture at distal, middle, and proximal positions on the balloon; average thicknesses were determined to be 16.4 ±â€¯5.8, 14.8 ±â€¯1.4, and 18.1 ±â€¯3.9 µm, respectively. These optimized coating conditions have been confirmed by in vitro drug release kinetics studies. Overall this study generated a simple and reproducible micro-pipetting coating method for the sustained release of drugs from the drug coated balloons.


Assuntos
Sistemas de Liberação de Medicamentos , Excipientes/química , Iohexol/análogos & derivados , Paclitaxel/administração & dosagem , Angioplastia Coronária com Balão/instrumentação , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Iohexol/química , Microscopia Eletrônica de Varredura/métodos , Paclitaxel/química , Reprodutibilidade dos Testes , Tecnologia Farmacêutica/métodos
2.
J Biomed Mater Res B Appl Biomater ; 106(6): 2393-2402, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29178263

RESUMO

Liners used in orthopedic devices are often made from ultrahigh molecular weight polyethylene (UHMWPE). A general predictive capability for transport coefficients of small molecules in UHMWPE does not exist, making it difficult to assess properties associated with leaching or uptake of small molecules. To address this gap, we describe here how a form of the Vrentas-Duda free volume model can be used to predict upper-bound diffusion coefficients (D) of arbitrary molecules within UHMWPE on the basis of their size and shape. Within this framework, the free-volume microstructure of UHMWPE is defined by analysis of a curated set of model diffusants. We determined an upper limit on D for vitamin E, a common antioxidant added to UHMWPE, to be 7.1 × 10-12 cm2  s-1 . This means that a liner that contains 0.1 wt % or less Vitamin E and has <120 cm2 patient contacting surface area would elute <100 µg/day of vitamin E. Additionally, the model predicts that squalene and cholesterol-two pro-oxidizing biological compounds-do not penetrate over 820 µm into UHMWPE liners over the course of 5 years because their D is ≤7.1 × 10-12 cm2  s-1 . © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2393-2402, 2018.


Assuntos
Materiais Revestidos Biocompatíveis/química , Prótese de Quadril , Teste de Materiais , Polietilenos/química , Humanos
3.
J Biomech Eng ; 136(2): 021027, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24317017

RESUMO

The objective of this study is to develop a theoretical model to simulate temperature fields in a joint simulator for various bearing conditions using finite element analyses. The frictional heat generation rate at the interface between a moving pin and a stationary base is modeled as a boundary heat source. Both the heat source and the pin are rotating on the base. We are able to conduct a theoretical study to show the feasibility of using the COMSOL software package to simulate heat transfer in a domain with moving components and a moving boundary source term. The finite element model for temperature changes agrees in general trends with experimental data. Heat conduction occurs primarily in the highly conductive base component, and high temperature elevation is confined to the vicinity of the interface in the pin. Thirty rotations of a polyethylene pin on a cobalt-chrome base for 60 s generate more than 2.26 °C in the temperature elevation from its initial temperature of 25 °C at the interface in a baseline model with a rotation frequency of 0.5 Hz. A higher heat generation rate is the direct result of a faster rotation frequency associated with intensity of exercise, and it results in doubling the temperature elevations when the frequency is increased by100%. Temperature elevations of more than 7.5 °C occur at the interface when the friction force is tripled from that in the baseline model. The theoretical modeling approach developed in this study can be used in the future to test different materials, different material compositions, and different heat generation rates at the interface under various body and environmental conditions.


Assuntos
Desenho Assistido por Computador , Transferência de Energia , Análise de Falha de Equipamento/instrumentação , Análise de Falha de Equipamento/métodos , Prótese de Quadril , Modelos Teóricos , Temperatura , Simulação por Computador , Fricção , Condutividade Térmica
4.
J Biomed Mater Res B Appl Biomater ; 101(7): 1191-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23564439

RESUMO

Drug-polymer composite coatings, composed of styrene-isobutylene-styrene (SIBS) tri-block copolymers, are frequently used in controlled drug release biomedical device applications. In this work, we used atomic force microscopy to characterize the effects of different drug loadings and polymer chemistries (i.e., block copolymer ratio) on the variation of surface structures and compositions of SIBS-tetracycline (SIBS-TC) cast composites including tetracycline (TC) drug amount, drug phase size distribution, and drug and polymer phase morphologies. We tested the structural variations by fabricating and characterizing two types of composite specimens, that is, SIBS15 and SIBS30, composed of 15 and 30 Wt % of polystyrene (PS), respectively. The differences in the distribution of TC drug, PS, and polyisobutylene (PIB) polymer phase structures observed in SIBS15 and SIBS30 resulted in more drug at the surface of SIBS30 compared to SIBS15. To support the experimental findings, we have determined the Hildebrand solubility parameter of TC using molecular dynamics (MD) computation and compared it to the polymer components, PS and PIB. The MD results show that the solubility parameter of TC is much closer to that of PS than PIB, which demonstrates a higher thermodynamic stability of TC-PS mixtures.


Assuntos
Antibacterianos/química , Sistemas de Liberação de Medicamentos , Estirenos/química , Tetraciclina/química
5.
J Pharm Sci ; 99(6): 2777-85, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20091828

RESUMO

A critical metrology issue for pharmaceutical industries is the application of analytical techniques for the characterization of drug delivery systems to address interrelationships between processing, structure, and drug release. In this study, cast coatings were formed from solutions of poly(styrene-b-isobutylene-b-styrene) (SIBS) and tetracycline in tetrahydrofuran (THF). These coatings were characterized by several imaging modalities, including time-of-flight secondary ion mass spectrometry (TOF-SIMS) for chemical imaging and analysis, atomic force microscopy (AFM) for determination of surface structure and morphology, and laser scanning confocal microscopy (LSCM), which was used to characterize the three-dimensional structure beneath the surface. The results showed phase separation between the drug and copolymer regions. The size of the tetracycline phase in the polymer matrix ranged from hundreds of nanometers to tens of microns, depending on coating composition. The mass of drug released was not found to be proportional to drug loading, because the size and spatial distribution of the drug phase varied with drug loading and solvent evaporation rate, which in turn affected the amount of drug released.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/análise , Polímeros/química , Solventes/química , Espectrometria de Massa de Íon Secundário/métodos , Antibacterianos , Formas de Dosagem , Microscopia de Força Atômica , Estirenos , Tetraciclina
6.
J Biomed Mater Res B Appl Biomater ; 90(2): 688-99, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19213052

RESUMO

To improve functionality and performance, controlled drug-release coatings comprised of drug and polymer are integrated with traditional medical devices, e.g., drug eluting stents. Depending on manufacturing conditions, these coatings can exhibit complex microstructures. Previously, a thermodynamically consistent model was developed for microstructure evolution in these systems to establish relationships between process variables, microstructure, and the subsequent release kinetics. Calculations based on the model were, in general, consistent with experimental findings. However, because of assumptions regarding the evaporation of solvent during fabrication, the model was unable to capture variations through the coating thickness that are observed experimentally. Here, a straightforward method is introduced to incorporate solvent evaporation explicitly into the model. Calculations are used to probe the impact of solvent evaporation rate and drug loading on the microstructure that forms during manufacturing and subsequent drug release kinetics. The predicted structures and release kinetics are found to be consistent with experimental observations. Further, the calculations demonstrate that solvent evaporation rate can be as critical to device performance as the amount of drug within the coating. For example, changes of a factor of five in the amount of drug released were observed by modifying the rate of solvent evaporation during manufacturing.


Assuntos
Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos , Solventes/química , Antibacterianos/administração & dosagem , Química Farmacêutica/métodos , Materiais Revestidos Biocompatíveis , Simulação por Computador , Desenho de Fármacos , Cinética , Microscopia Confocal/métodos , Modelos Estatísticos , Reprodutibilidade dos Testes , Tetraciclina/administração & dosagem , Termodinâmica
7.
Acta Biomater ; 2(5): 537-46, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16844438

RESUMO

Hematopoietic stem cell (HSC) therapy can significantly lower instances of infection in chemotherapy patients by accelerating the recovery of white blood cells in the body. However, therapy requires that HSCs be stored at cryogenic temperatures to retain the cells' ability to proliferate. Currently, cells are stored in polymeric blood bags that are subject to fracture at the extremely low storage temperatures, which leads to cell contamination, thereby reducing their effectiveness. Therefore, we have developed an analytical model to predict the accumulation of stresses that ultimately lead to crack initiation and bag fracture during cryogenic storage. Our model gives explicit relationships between stress state in the container and thermoelastic properties of the container material, container geometry, and environmental factors that include temperature of the system and pressure induced by excess gas evolving from the stored medium. Predictions based on the model are consistent with experimental observations of bag failures that occurred during cryogenic storage applications. Finally, the model can provide guidance in material selection and bag design to fabricate bags that will be less susceptible to fracture.


Assuntos
Criopreservação/métodos , Células-Tronco Hematopoéticas , Antineoplásicos/efeitos adversos , Materiais Biocompatíveis , Criopreservação/instrumentação , Elasticidade , Desenho de Equipamento , Transplante de Células-Tronco Hematopoéticas , Humanos , Técnicas In Vitro , Leucopenia/induzido quimicamente , Leucopenia/terapia , Teste de Materiais , Modelos Teóricos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Polímeros , Estresse Mecânico , Transplante Autólogo
8.
J Biomed Mater Res B Appl Biomater ; 77(2): 416-22, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16278851

RESUMO

An adhesive that cures under moist/wet conditions could facilitate surgical procedures for retinal reattachment. We are investigating an adhesive that mimics the factor XIIIa-mediated crosslinking of fibrin that occurs in the late stages of the blood coagulation cascade. Specifically, we use gelatin as the structural protein (in place of fibrin), and crosslink gelatin using a calcium-independent microbial transglutaminase (in place of the calcium-dependent transglutaminase factor XIIIa). Injection of gelatin and microbial transglutaminase (mTG) into the vitreous cavity of Sprague Dawley white rats did not elicit structural or cellular damage to the retina as evidenced from histological evaluation 2 weeks post-injection. Qualitative in vitro studies indicate that the gelatin-mTG adhesive binds to bovine retinal tissue under wet conditions. Quantitative lap-shear tests were performed with more robust bovine tissue from the choroid and sclera. The lap-shear strength of the biomimetic gelatin-mTG adhesive was independent of tissue-type and ranged from 15 to 45 kPa, which is comparable to the values reported for other soft-tissue adhesives. These studies suggest that the mTG-crosslinked gelatin may provide a simple, safe, and effective adhesive for ophthalmic applications.


Assuntos
Gelatina/administração & dosagem , Descolamento Retiniano/terapia , Adesivos Teciduais/química , Adesividade , Animais , Materiais Biomiméticos , Bovinos , Fator XIIIa/administração & dosagem , Fator XIIIa/metabolismo , Gelatina/síntese química , Injeções , Ratos , Ratos Sprague-Dawley , Retina , Resistência ao Cisalhamento
9.
Biomacromolecules ; 5(4): 1270-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15244440

RESUMO

Fibrin sealants are a type of soft tissue adhesive that employs biochemical reactions from the late stages of the blood coagulation cascade. Intrinsic to these adhesives are a structural protein and a transglutaminase crosslinking enzyme. We are investigating an alternative biomimetic adhesive based on gelatin and a calcium-independent microbial transglutaminase (mTG). Rheological measurements show that mTG catalyzes the conversion of gelatin solutions into hydrogels, and gel times are on the order of minutes depending on the gelatin type and concentration. Tensile static and dynamic loading of the adhesive hydrogels in bulk form demonstrated that the Young's modulus ranged from 15 to 120 kPa, and these bulk properties were comparable to those reported for hydrogels obtained from fibrin-based sealants. Lap-shear adhesion tests of porcine tissue were performed using a newly published American Society for Testing and Materials (ASTM) standard for tissue adhesives. The gelatin-mTG adhesive bound the opposing tissues together with ultimate adhesive strengths of 12-23 kPa which were significantly higher than the strength observed for fibrin sealants. Even after failure, strands of the gelatin-mTG adhesive remained attached to both of the opposing tissues. These results suggest that gelatin-mTG adhesives may offer the benefits of fibrin sealants without the need for blood products.


Assuntos
Materiais Biomiméticos/química , Reagentes de Ligações Cruzadas/química , Gelatina/química , Adesivos Teciduais/química , Transglutaminases/química , Animais , Catálise , Elasticidade , Adesivo Tecidual de Fibrina/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Técnicas In Vitro , Teste de Materiais , Reologia , Estresse Mecânico , Suínos , Fatores de Tempo
10.
Biomacromolecules ; 4(6): 1558-63, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14606880

RESUMO

We report an enzyme-based method for the in situ entrapment of cells within a biopolymeric hydrogel matrix. Specifically, we used a calcium-independent microbial transglutaminase that is known to cross-link proteins and observed that it catalyzes the formation of gels from a pre-gel solution containing 10% gelatin and E. coli cells. Hydrogel formation occurs 2-3 h after adding transglutaminase, and no additional external intervention is required to initiate gel formation. The in situ entrapped cells grow rapidly and to high cell densities within the gelatin hydrogel. Additionally, the entrapped cells respond to isopropylthiogalactoside induction. The cross-linked gelatin network can be rapidly hydrolyzed (within 1 h) by the protease, proteinase K. Treatment of the network by this protease releases the entrapped E. coli cells. These cells appear unharmed by proteinase K; they can grow and be induced after protease treatment. The ability to in situ entrap, grow, and release cells under mild conditions provides unique opportunities for a range of applications and should be especially useful for microfluidic biosensor systems.


Assuntos
Escherichia coli/citologia , Hidrogéis/síntese química , Transglutaminases/metabolismo , Proteínas de Bactérias/metabolismo , Técnicas Biossensoriais , Técnicas de Cultura de Células/métodos , Sobrevivência Celular , Gelatina/química , Proteínas de Fluorescência Verde , Proteínas Luminescentes
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