RT info:eu-repo/semantics/bachelorThesis
T1 Vehiculization of drugs with antiproliferative activity in protein nanoparticles as an alternative to pegylation to increase their circulation time in blood
A1 Rodríguez Méndez, Sheyla María
A2 Grado En Farmacia
K1 Colchicine
K1 Nanoparticles
K1 BSA
K1 Vehiculización
K1 Nanopartículas
K1 Albúmina
K1 Colchicina
K1 Biodisponibilidad
AB Nanoparticles are colloidal vehiculization systems that are increasinglyused by the scientific community to achieve the transport of drugs towardsspecific targets, improving their bioavailability, blood circulation and cellinternalization. In particular, PEGylation of nanoparticles is a method in whichnanoparticles are coated with polyethylene-glycol, achieving better efficiency indrug administration and increasing blood circulation time, but also reducingimmunogenicity. Among the different alternatives to PEGylation, it is remarkablethe use of albumin for the synthesis/coating of nanoparticles since, apart fromimproving the tumour accumulation of the transporters by means of the enhancedpermeability retention effect, the incorporation of this protein results in theinhibition of the non–specific adsorption of plasma proteins, decreasingopsonization processes.In this work, albumin-based nanoparticles have been synthesized by thedesolvation method, using glutaraldehyde as crosslinker. These nanoparticlespresented an average size of 131.55±2.62nm, a low polydispersity index rangedbetween 0.043-0.085 and a negative surface charge ranged between -30 and -48 mV. The particles were loaded with colchicine as a model cytotoxic drug thatacts by binding to tubulin that prevent mitotic division, achieving encapsulationefficiencies between 50-60%.Moreover, the colchicine-loaded nanoparticles were tested in HeLa andSW1573 cancer cells lines, performing clonogenic and antiproliferative assays.As conclusion, colchicine alone is more active than incorporated intonanoparticles, where it had a cytostatic activity. Thus, a concentration of 5 nM ofcolchicine is needed to inhibit growth by 50% and using nanoparticles aconcentration of > 50 µM is required to achieve the same effect.
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/24045
UL http://riull.ull.es/xmlui/handle/915/24045
LA es
DS Repositorio institucional de la Universidad de La Laguna
RD 30-abr-2024