Browsing by Author "Remuñán-López, Carmen"
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- Biocompatibility of chitosan carriers with application in drug deliveryPublication . Rodrigues, Susana; Dionísio, Marita; Remuñán-López, Carmen; Grenha, AnaChitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.
- Chitosan and its derivatives as nanocarriers for siRNA deliveryPublication . Al-Qadi, Sonia; Grenha, Ana; Remuñán-López, CarmenThe ability to specifically silence genes using siRNA has enormous potential for treating genetic diseases. However, siRNA instability and biodistribution issues still need to be overcome, and adequate delivery vehicles have proven indispensable in conveying siRNA to its target. Chitosan is a promising biopolymer for siRNA delivery, its interest stemming from its safety, biodegradability, mucoadhesivity, permeation enhancing effect and cationic charge, as well as amenability to undergo chemical modifications. Chitosan and its derivatives can be readily arranged into complexes or nanoparticles able to entrap and carry siRNA. Specific strategies have been adopted to improve chitosan-based vectors with regard to transfectability. However, further efforts are required to verify their value and adapt them to enhance therapeutic output prior to clinical application. This review emphasizes the potential of chitosan and its derivatives to develop nanocarriers for siRNA delivery. The properties of chitosan that are significant for transfectability and the most relevant findings are assessed.
- Microspheres loaded with polysaccharide nanoparticles for pulmonary delivery: preparation, structure and surface analysisPublication . Al-Qadi, Sonia; Grenha, Ana; Remuñán-López, CarmenIn this work, we report the preparation of a nanoparticle-based dry powder for pulmonary administration. Hybrid chitosan/hyaluronic acid nanoparticles were produced by ionotropic gelation and characterized for their physicochemical properties, being further studied by solid nuclear magnetic resonance (NMR). Using mannitol as carrier, nanoparticles were microencapsulated by spray drying, resulting in a dry powder with appropriate aerodynamic properties for lung delivery. In order to investigate the nanoparticles distribution within the carrier matrix, several techniques were applied that permitted an in-depth analysis of the system structure and surface, such as confocal laser scanning microscopy (CLSM) and X-ray photoelectron spectroscopy (XPS) in combination with time-of-flight secondary ion mass spectroscopy (TOF-SIMS). Overall, the studies conducted revealed that nanoparticles are homogeneously distributed through mannitol microspheres, suggesting the success of the microencapsulation process. In the light of these findings, it was concluded that the developed delivery system holds great potential for lung delivery of macromolecules.
- Mucosal delivery of liposome-chitosan nanoparticles complexesPublication . Carvalho, Edison Samir Mascarelhas; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, BegoñaDesigning adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.
- Pullulan-based nanoparticles as carriers for transmucosal protein deliveryPublication . Dionísio, Marita; Cordeiro, Clara; Remuñán-López, Carmen; Seijo, Begoña; Costa, Ana M. Rosa da; Grenha, AnaPolymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up. In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.
- The potential of chitosan for pulmonary drug deliveryPublication . Grenha, Ana; Al-Qadi, Sonia; Seijo, Begoña; Remuñán-López, CarmenThe administration of drugs through the pulmonary route offers great advantages, but also requires overcoming many challenges. There is a need to develop appropriate carriers for each active molecule to be delivered to the desired site in the lung, either for a local or a systemic effect. The polysaccharide chitosan is a very promising material for this purpose, given its demonstrated properties of biodegradability and biocompatibility, as well as mucoadhesivity and ability to enhance macromolecules permeation. In this review, the potential of chitosan to develop drug carriers for delivery to the lung will be discussed. The most important features that can support its selection will be explained. Besides, different approaches to increase its performance, especially concerning solubility, permeation-enhancing properties and gene transfection efficiency, will be presented. Special emphasis will be placed on information of different chitosan-based carriers, namely nanoparticles and microparticles, intended for pulmonary drug delivery.