Staff member

Mireia Oliva Herrera

Senior Researcher
Nanoprobes and Nanoswitches
+34 934 024 549
Staff member publications

Giannotti, Marina I., Abasolo, Ibane, Oliva, Mireia, Andrade, Fernanda, García-Aranda, Natalia, Melgarejo, Marta, Pulido, Daniel, Corchero, José Luis, Fernández, Yolanda, Villaverde, Antonio, Royo, Miriam, Garcia-Parajo, Maria F., Sanz, Fausto, Schwartz Jr, Simó, (2016). Highly versatile polyelectrolyte complexes for improving the enzyme replacement therapy of lysosomal storage disorders ACS Applied Materials & Interfaces 8, (39), 25741–25752

Lysosomal storage disorders are currently treated by enzyme replacement therapy (ERT) through the direct administration of the unprotected recombinant protein to the patients. Herein we present an ionically cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and

Keywords: Enzyme replacement therapy, Fabry disease, Lysosomal delivery, Nanomedicine, Polyelectrolyte complexes, Trimethyl chitosan, α-galactosidase A

Andrade, F., Neves, J. D., Gener, P., Schwartz, S., Ferreira, D., Oliva, M., Sarmento, B., (2015). Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin Nanomedicine: Nanotechnology, Biology, and Medicine 11, (7), 1621-1631

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<. 6. μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. From the Clinical Editor: The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies.

Keywords: Cytotoxicity, Inhalation, Permeability, Phagocytosis, Polymeric micelles, Protein delivery

Andrade, F., Fonte, P., Oliva, M., Videira, M., Ferreira, D., Sarmento, B., (2015). Solid state formulations composed by amphiphilic polymers for delivery of proteins: Characterization and stability International Journal of Pharmaceutics 486, (1-2), 195-206

Abstract Nanocomposite powders composed by polymeric micelles as vehicles for delivery proteins were developed in this work, using insulin as model protein. Results showed that size and polydispersity of micelles were dependent on the amphiphilic polymer used, being all lower than 300 nm, while all the formulations displayed spherical shape and surface charge close to neutrality. Percentages of association efficiency and loading capacity up to 94.15 ± 3.92 and 8.56 ± 0.36, respectively, were obtained. X-ray photoelectron spectroscopy (XPS) measurements confirmed that insulin was partially present at the hydrophilic shell of the micelles. Lyophilization did not significantly change the physical characteristics of micelles, further providing easily dispersion when in contact to aqueous medium. The native-like conformation of insulin was maintained at high percentages (around 80%) after lyophilization as indicated by Fourier transform infrared spectroscopy (FTIR) and far-UV circular dichroism (CD). Moreover, Raman spectroscopy did not evidenced significant interactions among the formulation components. The formulations shown to be physically stable upon storage up to 6 months both at room-temperature (20 C) and fridge (4 C), with only a slight loss (maximum of 15%) of the secondary structure of the protein. Among the polymers tested, Pluronic® F127 produced the carrier formulations more promising for delivery of proteins.

Keywords: Amphiphilic polymers, Insulin, Lyophilization, Polymeric micelles, Stability

Giannotti, M. I., Esteban, O., Oliva, M., Garcia-Parajo, M. F., Sanz, F., (2011). pH-Responsive polysaccharide-based polyelectrolyte complexes as nanocarriers for lysosomal delivery of therapeutic proteins Biomacromolecules American Chemical Society 12, (7), 2524-2533

Nanopharmaceutics composed of a carrier and a protein have the potential to improve the activity of therapeutical proteins. Therapy for lysosomal diseases is limited by the lack of effective protein delivery systems that allow the controlled release of specific proteins to the lysosomes. Here we address this problem by developing functional polyelectrolyte-based nanoparticles able to promote acidic pH-triggered release of the loaded protein. Trimethyl chitosan (TMC) was synthesized and allowed to form polyelectrolyte complexes (PECs) with the lysosomal enzyme

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