RESUMEN
The coating material technology is important for the delivery of anti-proliferative drugs from the surface of drug-eluting balloons (DEBs), which are emerging as alternatives to drug-eluting stents (DES) in the field of interventional cardiology. Currently, several shortcomings limit their competition with DES, including low drug transfer efficiency to the arterial tissues and undesirable particulate generation from the coating matrix. In this review, we provide a survey of the materials used in existing DEBs, and discussed the mechanisms of actions of both the drugs and coating materials. The type of drug and the influence of the coating material characteristics on the drug uptake, distribution and retention in arterial tissues are described. We also summarize the novel coating excipients under development and provide our perspective on the possible use of nano-scale carriers to address the shortcomings of current coating technology. The scope of this review includes only materials that have been approved for biomedical applications or are generally recognized as safe (GRAS) for drug delivery.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/tendencias , Stents Liberadores de Fármacos/tendencias , Ensayo de Materiales/métodos , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Paclitaxel/administración & dosificación , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/metabolismo , Diseño de Prótesis/métodos , Diseño de Prótesis/tendenciasRESUMEN
AIMS: While bioresorbable vascular scaffolds (BVS) are increasingly used in clinical practice, their behaviour when post-dilated beyond their recommended maximum overexpansion diameter remains sparsely documented. We aimed to test the overexpansion of the BVS scaffold in vitro and evaluate the impact of excessive scaffold oversizing on focal point support. METHODS AND RESULTS: We examined the post-expansion behaviour of the bioresorbable vascular scaffold (3.0 mm and 3.5 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) after overexpansion with non-compliant (NC) balloons of increasing diameters. After each oversizing step, the scaffolds were measured and inspected for strut disruption using microscope and optical coherence tomography imaging. Point force mechanical measurements on single scaffold struts were also performed to evaluate the impact of excessive scaffold overstretching on focal mechanical support. 3.0 mm and 3.5 mm scaffold sizes could be post-expanded up to 1 mm above their nominal diameters without any strut fracture when deployed without an external constraining model. Importantly, when overexpansion of both scaffold sizes was repeated using a constraining silicone lesion model, only post-expansion with an NC balloon size 0.5 mm larger than the scaffold nominal sizes could be performed without strut fractures. Point force compression analysis on single struts shows that overstretched struts with fractures provided lower focal strength compared to overexpanded ring segments without fractures and normal segments expanded at nominal pressure. CONCLUSIONS: In our experiments, only overexpansion with an NC balloon 0.5 mm larger than the BVS size was feasible for BVS deployed inside an arterial lesion model. Overexpansion of the BVS scaffold beyond recommended post-dilation limits can lead to strut disconnections and focal loss of mechanical support.
Asunto(s)
Implantes Absorbibles , Angioplastia Coronaria con Balón/instrumentación , Catéteres Cardíacos , Falla de Prótesis , Angioplastia Coronaria con Balón/efectos adversos , Análisis de Falla de Equipo , Ensayo de Materiales , Modelos Anatómicos , Modelos Cardiovasculares , Diseño de Prótesis , Siliconas , Estrés Mecánico , Resistencia a la TracciónRESUMEN
The purpose of this study was to develop a fully degradable occluder for the closure of PDA, which can be deployed percutaneously. The blends of biodegradable poly(ε-caprolactone) and poly(L-lactide-co-ε-caprolactone) with various compositions were studied as the potential material. The mechanical properties, i.e. elastic modulus and strain recovery, of the blends could be largely tailored by changing the continuous phase component. Moreover, the suitable blends were selected to fabricate a prototype and its in vitro biodegradation rate and blood compatibility, was evaluated. The current results indicate that no adverse effect on the platelet and leukocyte components of the blood. Biocompatibility implantation studies of the device showed acceptable tissue response. Finally, an artificial PDA conduit was created in a pig, and the device deployment was tested from a sheath: the device recovered within 2-3 min of unsheathing and fully sealed the conduit.
Asunto(s)
Implantes Absorbibles , Conducto Arterioso Permeable/cirugía , Implantes Absorbibles/efectos adversos , Animales , Materiales Biocompatibles/efectos adversos , Materiales Biocompatibles/química , Fenómenos Biomecánicos , Estudios de Factibilidad , Humanos , Técnicas In Vitro , Recuento de Leucocitos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Modelos Animales , Recuento de Plaquetas , Poliésteres/química , Diseño de Prótesis , Porcinos , Porcinos Enanos , Oclusión Terapéutica/efectos adversos , Oclusión Terapéutica/instrumentación , Trombosis/etiología , Factores de Tiempo , Andamios del Tejido/efectos adversos , Andamios del Tejido/químicaRESUMEN
Patent Ductus Arteriosus (PDA) is a cardiovascular defect that occurs in 1 out of every 2000 births, and if left untreated, may lead to severe cardiovascular problems. Current options for occluding utilize meta scaffolds with polymer fabric, and are permanent. The purpose of this study was to develop a fully degradable occluder for the closure of PDA, that can be deployed percutaneously without open-heart surgery. For percutaneous deployment, both elasticity and sufficient mechanical strength are required of the device components. As this combination of properties is not achievable with currently-available homo- or copolymers, blends of biodegradable poly(ε-caprolactone) (PCL) and poly(L-lactide-co-ε-caprolactone) (PLC) with various compositions were studied as the potential material for the PDA occlusion device. Microstructures of this blend were characterized by differential scanning calorimetry (DSC) and tensile tests. DSC results demonstrated the immiscibility between PCL and its copolymer PLC. Furthermore, the mechanical properties, i.e. elastic modulus and strain recovery, of the blends could be largely tailored by changing the continuous phase component. Based on the thermo-mechanical tests, suitable blends were selected to fabricate a prototype of PDA occluder and its in vitro performance, in term of device recovery (from its sheathed configuration), biodegradation rate and blood compatibility, was evaluated. The current results indicate that the device is able to recover elastically from a sheath within 2-3min for deployment; the device starts to disintegrate within 5-6 months, and the materials have no adverse effects on the platelet and leucocyte components of the blood. Biocompatibility implantation studies of the device showed acceptable tissue response. Finally, an artificial PDA conduit was created in a pig model, and the device deployment was tested from a sheath: the device recovered within 2-3min of unsheathing and fully sealed the conduit, the device remains stable and is completely covered by tissue at 1 month follow up. Thus, a novel prototype for PDA occlusion that is fully degradable has been developed to overcome the limitations of the currently used metal/fabric devices.