RESUMEN
BACKGROUND: Polymer-based nanoparticles as drug-delivery systems offer new therapeutic opportunities. Among them, ligand-mediated targeting, which increases selectivity and efficacy, allows controllable drug delivery. The aim of the this research was to prepare and characterize poly(methyl methacrylate) (PMMA) nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed at the sites of integrin receptor overexpression. METHODS: Nanoparticles were characterized by FT-IR and Raman spectroscopy, dynamic light scattering, zeta potential and transmission electron microscopy. RESULTS: RGD-PMMA-PTX size distribution was 17.58 ± 7.45 nm with a zeta potential of -38.73 ± 5.62 mV. According to the boxLucas Model, PTX was incorporated into nanoparticles with an entrapment efficiency of 100% (evaluated by HPLC analysis). In vitro sustained release was determined, with the maximum release of 55% and 40% after 21 days at pH 5.3 and 7.4, respectively. The highest inhibition on cell proliferation was found with RGD-PMMA-PTX nanoparticles (90 %). CONCLUSION: The obtained results showed that RGD-PMMA-PTX represents an attractive and suitable therapeutic approach for targeting overexpressed integrins in the cancer cells.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Oligopéptidos/administración & dosificación , Paclitaxel/administración & dosificación , Polimetil Metacrilato/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Oligopéptidos/química , Oligopéptidos/metabolismo , Paclitaxel/química , Paclitaxel/metabolismo , Tamaño de la Partícula , Polimetil Metacrilato/química , Polimetil Metacrilato/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Espectrometría Raman/métodosRESUMEN
BACKGROUND: The nanomedicine is considered as the application of nanotechnology in the medical field where nanoparticles are sized in the nanoscale range. Drug delivery technologies are becoming increasingly important as a scientific area of investigation. Controlled-release systems and drug-targeting systems represents an alternative to traditional delivery nanoparticles, and the use of polymers is increasing nowadays. Although polymers could be classified as excipients, they are capable of modifying the biopharmaceutical and biokinetic behaviour of the transported active molecule increasing its efficacy and stability, and reduced cytotoxicity on healthy peripheral tissues. METHODS: The goal of this work is to collect and analyse the most current polymeric nanoparticles development as controlledrelease and drug-targeting systems in cancer, infectious diseases and immunomodulation areas, as alternatives to conventional therapies. RESULTS: This review provides an update on the polymeric nanoparticles development analysing the trend of polymeric-based drug delivery systems, future opportunities and challenges of this fast-growing area. CONCLUSION: With the thorough comprehension of biological effects depending on structure, it is possible to design specific systems for specific diseases, treatments and patients. The ability of polymer- based nanoparticles to modify and improve pharmacokinetics and pharmacodynamics, associated to techniques for enhancement of the therapeutic efficiency with minimal side effects, demonstrate the advantages of these systems.