ABSTRACT
BACKGROUND: Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. RESULTS: ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. CONCLUSION: Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments.
Subject(s)
Drug Delivery Systems/methods , Elastin/chemistry , Polymers/chemistry , Biocompatible Materials/chemistry , Drug Carriers/chemistry , Humans , Nanoparticles/chemistryABSTRACT
This Review discusses the use of elastin-like polymers and their recombinant version, elastin-like recombinamers, in drug-delivery systems. These macromolecules exhibit a number of interesting properties that are rarely found together in any other family of materials, especially extremely high biocompatibility, high bioactivity and functionality, complex yet fully controlled composition, and stimuli responsiveness. Appropriate design of these molecules opens up a broad range of different possibilities for their use in new therapeutic platforms. The first of these described herein is the use of ELRs in single-molecule devices as therapeutic entities in their own right. Subsequently, we describe how the self-assembly properties of these materials can be exploited to create nanocarriers and, eventually, microcarriers that are able to temporally and spatially control and direct the release of their drug load. Intracellular drug-delivery devices and nanocarriers for treating cancer are among the uses described in that section. Finally, the use of ELRs as base materials for implantable drug depots, in the form of hydrogels, is discussed.
Subject(s)
Drug Carriers/chemistry , Drug Delivery Systems/methods , Elastin/chemistry , Nanotechnology/methods , Animals , Humans , Hydrogels/chemistry , Recombinant Proteins/chemistryABSTRACT
El nuevo método desarrollado está dirigido a evaluar el riesgo derivado de la realización de tareas repetitivas a alta frecuencia. Utiliza un sistema de captura de movimiento basado en sensores inerciales, utilizable en los propios puestos de trabajo, que nos permite trasladar el movimiento a un modelo biomecánico de antropometría similar al sujeto observado. Incorpora un motor de cálculo de esfuerzos en las articulaciones, que tiene en cuenta las dimensiones antropométricas, las fuerzas externas, las reacciones en los puntos de apoyo, así como las fuerzas de inercia derivadas de las aceleraciones lineales y angulares alcanzadas durante la tarea. El resultado es un método predictivo de riesgo musculoesquelético que, a diferencia de otros métodos que requieren un trabajo muy minucioso (UNE 1005-3) a la hora de definir las acciones técnicas, reduce drásticamente el proceso de análisis ya que el proceso es automático, y no está influenciado por la subjetividad del evaluador.
The new method developed is aimed at assessing the risk from repetitive tasks at high frequency. It uses a motion capture system based on inertial sensors for use in their own jobs, which allows us to transfer the movement to a biomechanical model similar to the observed subject anthropometry. Incorporates a calculation engine of efforts in joints, considerating the anthropometric dimensions, external forces, the reactions in the support points, as well as the inertial forces arising from linear and angular accelerations encountered during the task. The result is a musculoskeletal risk predictive method which, unlike other methods that require a very thorough job (UNE 1005-3) for defining the technical actions, dramatically reduces the analysis process because the process is automated, and is not influenced by the subjectivity of the evaluator.
Subject(s)
Humans , Computer Simulation , Occupational Risks , Joints/physiology , Movement/physiology , Posture , Biomechanical Phenomena , Musculoskeletal Diseases/prevention & control , Risk Assessment/methods , Imaging, Three-Dimensional , ErgonomicsABSTRACT
This report examines the effect of FK506 pretreatment on liver insulin receptor expression in partially (70%) hepatectomized rats. FK506 pretreatment led to an increased insulin receptor number 24 hours after hepatectomy, detected by means of insulin binding and cross-linking procedures. This increase was related to enhanced insulin receptor expression determined by in vitro mRNA translation and Western blot techniques. We also tested the functionality of the expressed insulin receptors by [(3)H] thymidine incorporation into DNA in insulin-stimulated hepatocytes. The results show that FK506 pretreatment elicits an increase in the amount of insulin receptor alpha-subunits as measured by Western blot. Maximum alpha-subunit expression recorded 24 hours after surgery was preceded by increased insulin receptor mRNA levels, which were detected 6 hours after hepatectomy. Moreover, in FK506-pretreated rat hepatocytes, obtained from remnant livers 24 hours after partial hepatectomy (PH), the increase in insulin receptor number was associated with improved sensitivity to the hormone. However, in both experimental groups (FK506-pretreated and nonpretreated rats), the sensitivity of hepatocytes toward epidermal growth factor (EGF) showed no significant change, which suggests a specific effect of FK506 on insulin receptor expression. In conclusion, our findings suggest that FK506 pretreatment induces insulin receptor expression in regenerating rat liver and promotes liver regeneration in hepatectomized rats.
