Diseño y desarrollo de un sistema microparticular lipopolimérico para la administración de un péptido sintético modelo de naturaleza hidrofílica

dc.contributorRosas Pérez, Jaiver Eduardo
dc.contributorSistemas para liberación controlada de moléculas biológicamente activas (SILICOMOBA)
dc.creatorVelandia Paris, María Angélica
dc.date.accessioned2022-02-03T15:42:48Z
dc.date.available2022-02-03T15:42:48Z
dc.date.created2022-02-03T15:42:48Z
dc.date.issued2021
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/80864
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.description.abstractEn los últimos años se ha despertado un gran interés por los sistemas para la entrega de fármacos (SEF) mediante liberación controlada, debido a que permiten superar ciertas limitaciones de algunos ingredientes farmacéuticos activos (IFAs). Entre estos IFAs, se destacan los péptidos que, a pesar de ser degradados rápidamente, son moléculas esenciales en la vida debido a la posibilidad que tienen de cumplir múltiples funciones en el organismo, lo que ha permitido que sean considerados como IFA de elección para tratar numerosas enfermedades. Se ha reportado que los SEF particulados son capaces de proteger a moléculas lábiles como los péptidos de agentes externos como las enzimas, haciendo que se prolongue su tiempo de vida media y por tanto mejorando su actividad. Teniendo en cuenta esto se han diseñado diferentes SEF, entre ellos los liposomas, las partículas poliméricas y las partículas sólidas lipídicas, siendo estos sistemas los que han mostrado de manera general los mejores resultados como transportadores de IFAs. Producto de estas investigaciones, se ha mostrado un gran interés en desarrollar un SEF que permita reunir las ventajas de las partículas poliméricas y las partículas sólidas lipídicas, planteándose de esta forma el diseño y desarrollo de los sistemas híbridos lipopoliméricos. Con el propósito de contribuir en el campo de la investigación de SEF, en el marco de este trabajo se planteó el desarrollo una metodología para la obtención de tres sistemas particulados: micropartículas poliméricas, partículas sólidas lipídicas y micropartículas lipopoliméricas, empleando como material polimérico PLGA 50:50 (Viscosidad inherente: 0,8dL/g) y como material lipídico una mezcla de mono, di y triglicéridos C12-C18. Todos los sistemas se obtuvieron vacíos y cargados con un péptido sintético modelo de naturaleza hidrofílica, mediante la metodología de doble emulsión – evaporación del solvente Todos los sistemas fueron caracterizados en cuanto a morfología, tamaño, potencial Z, eficiencia de encapsulación y perfil de liberación del péptido. Como resultado, se logró obtener partículas en su mayoría esféricas de tamaño micrométrico para los sistemas poliméricos (3,08-5,60 µm) y lipopoliméricos (3,22-3,93 µm), de tamaño nanométrico para el sistema sólido lipídico (135,8-162,9 nm) y con un potencial Z entre -18,5mV y -24,5mV para las micropartículas poliméricas, -15,5mV y -29,9mV para las partículas sólidas lipídicas, -20,0mV y -26,1mV para las micropartículas lipopoliméricas. En cuanto a la eficiencia de encapsulación se determinó que el mejor sistema fue el de las micropartículas poliméricas con una E.E. promedio del 57,42% seguido de las micropartículas lipopoliméricas cuya E.E. promedio fue de 43,15% y las partículas sólidas lipídicas con una E.E. promedio del 40,40%. En referencia al perfil de liberación, se observó que las micropartículas lipopoliméricas tienden a mostrar un comportamiento intermedio entre los observados en las micropartículas poliméricas y en las partículas lipídicas. En conclusión, en este trabajo se desarrolló una metodología para la obtención y caracterización de un sistema micropartícular lipopolimérico que permite la encapsulación de un péptido sintético modelo de naturaleza hidrofílica con características tanto de micropartículas poliméricas (Tamaño y morfología) como de partículas sólidas lipídicas (E.E. y perfil de liberación). (texto tomado de la fuente)
dc.description.abstractIn recent years, controlled release drug delivery systems (DDS) have had great interest due they make possible to overcome certain limitations of some active pharmaceutical ingredients (APIs), between these APIs stand out peptides that despite of fast degradation, are essential molecules in life due to the possibility to accomplish multiple functions in the body, this has allowed to be considerate as choice API to treat numerous diseases. Particulate DDS have been shown to be able to protect labile molecules such as peptides from external agents such as enzymes, prolonging their half-life and therefore improving their activity. Bearing this in mind, different DDS have been designed, including liposomes, polymeric particles, and solid lipid particles, these being the ones that in general have shown better results as APIs carriers. As product of these research a great interest has been shown in developing a DDS that allows to have advantages of polymeric particles and solid lipid particles, proposing in this way the design and development of hybrid lipopolymeric systems. With the purpose of contribute to research field of DDS, within the framework of this work, the development of a methodology for the obtention of three particulate systems: Polymeric microparticles, solid lipid particles and lipopolymeric particles was proposed, using as polymeric material PLGA 50:50 (Inherent Viscosity 0,8 dL/g) and as lipidic material a mixture of mono, di and triglycerides C12-C18. All systems were obtained empty and loaded with a model synthetic peptide of hydrophilic nature using a methodology of double emulsion – solvent evaporation. All systems obtained were characterized in terms of morphology, size, Z potential, encapsulation efficiency and release profile. As result, was achieved particles mostly spherical, of micrometrical size for polymeric systems (3,08-5,60 µm) and lipopolymeric (3,22-3,93 µm), nanometrical size for the solid lipid system (135,8-162,9 nm), with a Z potential between -18,5mV -and -24,5mV for the polymeric particles, -15,5mV and -29,9mV for the solid lipid particles and -20,0mV and -26,1mV for the lipopolymeric particles. Regarding encapsulation efficiency, it was observed that lipopolymeric particles tend to show an intermediate behavior between the behavior observed in polymeric particles and in lipid particles. In conclusion, in this work a method was developed to obtain and characterize a lipopolymeric microparticle system that allows the encapsulation of a model synthetic peptide of a hydrophilic nature with characteristics of both polymeric particles (size and morphology) and solid lipid particles (E.E. and release profile).
dc.languagespa
dc.publisherUniversidad Nacional de Colombia
dc.publisherBogotá - Ciencias - Maestría en Ciencias Farmacéuticas
dc.publisherDepartamento de Farmacia
dc.publisherFacultad de Administración
dc.publisherBogotá, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
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dc.rightsAtribución-NoComercial-CompartirIgual 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDiseño y desarrollo de un sistema microparticular lipopolimérico para la administración de un péptido sintético modelo de naturaleza hidrofílica
dc.typeTrabajo de grado - Maestría


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