RESUMEN
Calcium phosphate cement (CPC) has been studied extensively due to its bioactivity and biodegradability. CPC is typically made by a combination of multiple calcium phosphates that form a paste that sets and hardens in the body after being combined with either water or an aqueous solution. It is highly moldable and easily manipulated, and CPCs possess osteoconductive properties. Due to these characteristics, CPCs offer great promise in bone grafting applications. CPC combined with drugs has a great potential as drug delivery system and has been studied extensively. In this review we have focused on Bisphosphonate-CPC drug delivery system. In addition, we introduce and discuss the potential of studying other bisphosphonates.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Fosfatos de Calcio/química , Difosfonatos/química , Portadores de Fármacos/química , Alendronato/administración & dosificación , Animales , Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos/métodos , Ácido Etidrónico/administración & dosificación , Humanos , Pamidronato/administración & dosificación , Ácido Zoledrónico/administración & dosificaciónRESUMEN
Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs. Such dual therapy restored vascular elastic lamina and improved vascular function as observed by improvement in circumferential strain. Therefore, dual targeted therapy may be an attractive option to remove mineral deposits and restore healthy arterial structures in moderately developed aneurysms.
Asunto(s)
Aneurisma de la Aorta/tratamiento farmacológico , Quelantes del Calcio/administración & dosificación , Ácido Edético/administración & dosificación , Taninos Hidrolizables/administración & dosificación , Nanopartículas/administración & dosificación , Polifenoles/administración & dosificación , Calcificación Vascular/tratamiento farmacológico , Animales , Aneurisma de la Aorta/patología , Arácnidos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Histocitoquímica , Ratas , Resultado del Tratamiento , Calcificación Vascular/patologíaRESUMEN
Degeneration of elastin plays a vital role in the pathology and progression of abdominal aortic aneurysm (AAA). Our previous study showed that pentagalloyl glucose (PGG), a core derivative of tannic acid, hinders the development of AAAs in a clinically relevant animal model when applied locally. In this study, we tested whether targeted nanoparticles (NPs) can deliver PGG to the site of an aneurysm and prevent aneurysmal growth by protecting elastin. PGG-loaded albumin NPs with a surface-conjugated elastin-specific antibody were prepared. Aneurysms were induced by calcium chloride-mediated injury to the abdominal aorta in rats. NPs were injected into the tail vein after 10 days of CaCl2 injury. Rats were euthanized after 38 days. PGG delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation, calcification, and development of aortic aneurysm. Such NP delivery offers the potential for the development of effective and safe therapies for AAA.