RESUMEN
Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.
Asunto(s)
Portadores de Fármacos/química , Compuestos Férricos/química , Heparina/química , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Transporte Biológico , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/metabolismo , Composición de Medicamentos/métodos , Liberación de Fármacos , Grasas/química , Compuestos Férricos/farmacología , Glicéridos/química , Heparina/metabolismo , Humanos , Absorción Intestinal , Modelos Biológicos , Nanopartículas/ultraestructura , Aceites/química , Tamaño de la Partícula , Electricidad Estática , Propiedades de SuperficieRESUMEN
Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe3O4·DA-BSA/HA in water. Fe3O4·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe3O4·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system.
Asunto(s)
Albúminas/química , Antineoplásicos Fitogénicos/administración & dosificación , Portadores de Fármacos , Ácido Hialurónico/química , Nanopartículas de Magnetita/química , Paclitaxel/administración & dosificación , Espectroscopía de Resonancia Magnética con Carbono-13 , Humanos , Células MCF-7 , Microscopía Electrónica de Transmisión , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Nanocellulose (NC) is getting ahead as a renewable, biodegradable and biocompatible biomaterial. The NCs for this study were recovered from industrial cotton waste (CFT) by acid hydrolysis (HNC) and by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation (ONC). They were functionalized by radical based glycidyl methacrylate (GMA) grafting providing crystalline HNC-GMA and ONC-GMA, and by allylation (ALL) providing amorphous HNC-ALL and ONC-ALL. HNC, ONC and their derivatives were chemically and morphologically characterized. Crystalline NCs were found capable to adsorb, from diluted water solution (2 × 10-3 M), the antibiotics vancomycin (VC), ciprofloxacin (CP), amoxicillin (AM) and the disinfectant chlorhexidine (CHX), while amorphous NCs did not show any significant adsorption properties. Adsorption capability was quantified by measuring the concentration change in function of the contact time. The adsorption kinetics follow the pseudo-second order model and show complex adsorption mechanisms investigated by an intraparticle diffusion model and interpreted by structure-property relationships. ONC and ONC-GMA loaded with VC, and HNC and HNC-GMA loaded with CP were not colonized by Staphylococcus aureus and by Klebsiella pneumonia and suggested long lasting release capability. Our results can envisage developing CFT derived NCs for environmental applications (water remediation) and for biomedical applications (antibacterial NC). Among the future developments, it could also be of interest to take advantage of acidic, glycidyl and allyl groups' reactivity to provide other NCs from the NC object of this study.
RESUMEN
Among nanocelluloses, bacterial nanocellulose (BNC) has proven to be a promising candidate in a range of biomedical applications, from topical wound dressings to tissue-engineering scaffolds. Chemical modifications and incorporation of bioactive molecules have been obtained, further increasing the potential of BNC. This study describes the incorporation of vancomycin and ciprofloxacin in BNC and in modified BNC to afford bioactive BNCs suitable for topical wound dressings and tissue-engineering scaffolds. BNC was modified by grafting glycidylmethacrylate (GMA) and further cross-linking with ethylene glycol dimethacrylate (EGDMA) with the formation of stable C-C bonds though a radical Fenton-type process that involves generation of cellulose carbon centred radicals scavenged by methacrylate structures. The average molar substitution degree MS (MS = methacrylate residue per glucose unit, measured by Fourier transform infrared (FT-IR) analysis) can be modulated in a large range from 0.1 up to 3. BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA maintain the hydrogel status until MS reaches the value of 1. The mechanical stress resistance increase of BNC-GMA and BNC-GMA-EGDMA of MS around 0.8 with respect to BNC suggests that they can be preferred to BNC for tissue-engineering scaffolds in cases where the resistance plays a crucial role. BNC, BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA were loaded with vancomycin (VC) and ciprofloxacin (CP) and submitted to release experiments. BNC-GMA-EGDMA of high substitution degree (0.7-1) hold up to 50 percentage of the loaded vancomycin and ciprofloxacin amount, suggesting that they can be further investigated for long-term antimicrobial activity. Furthermore, they were not colonized by Staphylococcus aureus (S.A.) and Klebsiella pneumonia (K.P.). Grafting and cross-linking BNC modification emerges from our results as a good choice to improve the BNC potential in biomedical applications like topical wound dressings and tissue-engineering scaffolds.