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Preparazione e caratterizzazione di Nanocarriers lipidici per il drug e gene delivery: vantaggi nel trattamento di patologie oculari, epatiche e polmonari. Prove biologiche in vitro dei sistemi preparati che hanno dimostrato i vantaggi dei sistemi preparati.

Loading of Curcumin intoLoading of Curcumin into Curcumin is a natural anti-cancer compound with proved efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanoparticle-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. Here, we describe the preparation of Nanostructured Lipid Carriers (NLCs) containing curcumin in attempt to evaluate the antitumoral activity of curcumin, free or entrapped into NLCs, against ovarian cancer cells. The obtained curcumin-loaded NLCs exhibited a controlled release profile of entrapped drug and showed in vitro improved anti- cancer potential by clonogenic assays compared to free curcumin. . Further, curcumin-loaded NLCs showed the same mechanisms of action of free curcumin, including the induction of cellular apoptosis. The obtained results clearly suggest that the entrapment of curcumin into NLCs increases drug efficacy in vitro against ovarian cancer cells compared to free curcumin, indicating the potential use of NLCs as curcumin drug delivery systems.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths. For the treatment of HCC several drugs are under development, but the only one with proven survival benefit is sorafenib. This agent is a multikinase inhibitor that blocks Raf signaling and VEGF, PDGF and c-Kit. It has antiproliferative and antiangiogenic activity and delays tumor progression [1,2]. Moreover, systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutic strategies. At this purpose a large number of viral and non-viral vectors have been studied and applied as systems of stable transfection with low toxicity. Although cationic polymers and liposome are promising systems, solid lipid nanoparticles (SLN) have been recently proved to be a really useful vehicle for gene therapy [3,4]. The aim of this work was to design and to obtain cationic SLNs containing sorafenib capable of forming complexes with siRNA and DNA plasmid for the treatment of HCC, in order to combine the effects of drug and nucleic acids. The physical binding between cSLN and nucleic acids was confirmed by the study of complexes’ zeta potential values that became more positive as higher was the amount of cSLN and via the electrophoretic mobility of the samples in agarose gel 0.8%. Transfection studies on different tumor cell line are in progress.

Central Nervous System (CNS) diseases represent the largest and fastest growing area of unmet medical need since an alarming increase in brain disease incidence is going on. Despite major advances in neuroscience, many potential therapeutic agents are denied access to the CNS because of the existence of a physiological low permeable barrier, the Blood-Brain Barrier (BBB). To obtain an improvement of drug CNS performance, sophisticated approaches such as nanoparticulate systems are rapidly developing. In particular, in this chapter, the most recent data demonstrating the potential of lipid nanostructures, such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC), to successfully transport drugs into the brain for the treatment of CNS diseases including Alzheimer's and Parkinson's diseases, cancer, mood disorder, AIDS, and bacterial infections, are summarised. Their use as drug delivery systems is associated with many advantages that include an excellent storage stability, a relatively easy production without the use of any organic solvent, the possibility of steam sterilization and lyophilization, and large scale production. Moreover, SLN and NLC are obtained by using physiologically well-tolerated ingredients already approved for pharmaceutical applications in humans and show low toxicity when administered. Because of their small size, these systems may be injected intravenously and avoid the uptake of macrophages of mononuclear phagocyte system (MPS). Moreover, their lipophilic features lead them to CNS by an endocytotic mechanism, overcoming the BBB.

Purpose of review The purpose of the present review is to underline the importance of nanoparticulate carriers, such as polymeric nanoparticles, in the future development of safe and effective formulation in the field of immunotherapy against infectious diseases and cancer. Recent findings Polymeric nanoparticles can modulate the immune response, that is, by targeting antigens to dendritic cells that possess a crucial role in initiating immune responses, and might be potentially useful in immunotherapy. Summary In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of infectious diseases and cancer. Polymeric nanoparticles are particularly adept at facilitating immunotherapeutic approaches because they can be engineered to have different physical properties, encapsulated agents, and surface ligands. Moreover, these systems are administrable for all routes, are capable of being actively taken up by dendritic cells and have shown promising potential in systemic and mucosal immunotherapy. Here, some recent findings on these systems, in their potential applications for infectious and cancer immunotherapy, are reported.

The prospect of improved cancer therapy using Solid Lipid Nanoparticles (SLNs) as drug delivery system is promising. Several obstacles frequently encountered with anticancer compounds, such as poor drug solubility, are overcome by delivering them using SLN. Moreover, the intravenous administration of drugs into SLNs can potentially enhance drug blood circulation time and improve drug performance by inducing accumulation into tumours by enhanced permeability and retention (EPR) effect. This paper deals with the development of SLN containing nimesulide, a non-steroidal anti-inflammatory drug with antitumour effect and low solubility in water. Here, SLNs carrying nimesulide were prepared and characterized, and the antiproliferative effect of drug-loaded SLN versus free drug on HT-29 and SW-480 cell lines was here evaluated. All the obtained systems possess colloidal size, ranging from 85 to 132 nm and negative zeta potential values. Moreover these systems show good loading capacity and drug release profile, and an in vitro antitumour activity comparable to free drug.

Solid lipid and polymeric nano particles systems containing drugs and genetic materials with great potential as drug and gene delivery systems were produced in the..........

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG2000 as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG2000 copolymer mixture as the internal phase and triacetin saturated with water as the external phase, and characterized by dimensional analysis, zeta-potential measurements and XPS. in vitro biological tests demonstrated their cell compatibility and their ability to escape from phagocytosis. Rivastigmine was encapsulated into the nanoparticle structure and drug-release profiles from loaded samples were investigated in PBS at pH¼7.4 and human plasma.

Gene transfer is an important advance in the treatment of both genetic and acquired diseases, since gene therapy is one of the most important weapons against cancer and genetic diseases. DNA and RNA as biological macromolecules have the potential characteristics for formation of nanostructures. Nanotechnology in the last decade has a great impact in life sciences. In this study the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain a new kind of vector able to condenseand protect RNA. We describe the production of a new type of cationic nanoparticles and we test their ability to form complexeswith RNA and their toxicity and biocompatible properties on a living organism as sea urchin.

This article describes the development of solid lipid nanoparticles (SLN) as colloidal carriers for cloricromene. Nanoparticles were prepared by the microemulsion or precipitation technique. In vitro drug release profile from SLN was studied under various experimental conditions mimicking some body fluids. The drug release rate of drug at pH 7.4 and human plasma is high. In plasma, after 15 min, about 70% of drug was released. The cloricromene that was not released within 4 hr was found in the SLN. This result suggests that this colloidal system could be useful for targeted drug delivery to the central nervous system after intravenous administration