ABSTRACT
Liver inflammation represents a major clinical problem in a wide range of pathologies. Among the strategies to prevent liver failure, dexamethasone (DXM) has been widely used to suppress inflammatory responses. The use of nanocarriers for encapsulation and sustained release of glucocorticoids to liver cells could provide a solution to prevent severe side effects associated with systemic delivery as the conventional treatment regime. Here we describe a nanostructured lipid carrier developed to efficiently encapsulate and release DXM. This nano-formulation proved to be stable over time, did not interact in vitro with plasma opsonins, and was well tolerated by primary non-parenchymal liver cells (NPCs). Released DXM preserved its pharmacological activity, as evidenced by inducing robust anti-inflammatory responses in NPCs. Taken together, nanostructured lipid carriers may constitute a reliable platform for the delivery of DXM to treat pathologies associated with chronic liver inflammation.
ABSTRACT
Plasmonic metal nanoparticles (NPs) can be used as enhancers of the efficiency of standard photosensitizers (PSs) in photodynamic therapy (PDT). Protein corona, the adsorption layer that forms spontaneously around NPs once in contact with biological fluids, determines to a great extent the efficiency of PDT. In this work, we explore the possibility that pectin-coated Au NPs (Au@Pec NPs) could act as adjuvants in riboflavin (Rf)-based PDT by comparing the photodamage in HeLa cells cultured in the presence and in the absence of the NPs. Moreover, we investigate the impact that the preincubation of Rf and Au@Pec NPs (or Ag@Pec NPs) at two very different serum concentrations could have on cell's photodamage. Because reactive oxygen species (ROS) precursors are the excited states of the PS, the effect of proteins on the photophysics of Rf and Rf/plasmonic NPs was studied by transient absorption experiments. The beneficial effect of Au@Pec NPs in Rf-based PDT on HeLa cells cultured under standard serum conditions was demonstrated for the first time. However, the preincubation of Rf and Au@Pec NPs (or Ag@Pec NPs) with serum has undesirable results regarding the enhancement of Rf-based PDT. In this sense, we also verified that more concentrated protein conditions result in lower amounts of the triplet excited state of Rf and thus an expected lower production of ROS, which are the key elements for PDT's efficacy. These findings point out the relevance of serum concentration in the design of in vitro cell culture experiments carried out to determine the best way to combine and use potential sensitizers with plasmonic NPs to develop more effective PDTs.
ABSTRACT
The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.
