SOLID LIPID NANOPARTICLES FOR APPLICATIONS IN GENE THERAPY: A REVIEW OF THE STATE OF THE ART

Importance of the field. Gene therapy represents a new paradigm in the prevention and treatment of many inherited and acquired diseases, including genetic disorders, such as cystic fibrosis, haemophilia and many somatic diseases, such as tumours, neurodegenerative diseases and viral infections, such as AIDS. Areas covered in this review. Among a large array of non-viral transfection agents used for in-vitro applications, cationic SLNs are the topic of this review, being recently proposed as an alternative carrier for DNA delivery, due to many technological advantages such as large-scale production from substances generally recognized as safe, good storage stability and possibility of steam …

Sesquiterpene lactones of Anthemis alpestris

Preparation of Polymeric Nanoparticles by Photo-Crosslinking of an Acryloylated Polyaspartamide in w/o Microemulsion

Biodegradable polymeric nanoparticles have been prepared by UV irradiation of an acryloylated water soluble polymer by an inverse microemulsion. The starting polymer was a α,β‐poly(N‐2‐hydroxyethyl)‐D,L‐aspartamide (PHEA) partially functionalized with glycidyl methacrylate (GMA) in order to introduce reactive vinyl groups in the side chain. The PHEA‐GMA copolymer obtained (PHG) was crosslinked by UV irradiation of the inverse microemulsion prepared by mixing an aqueous solution of PHG with propylene carbonate (PC)/ethyl acetate (EtOAc) in the presence of sorbitan trioleate (SPAN 85) as surfactant. Nanoparticles obtained were characterized by FTIR spectrophotometry, transmission electron mic…

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…

Mucoadhesive Solid Lipid Microparticles (SLM) for sustained release of corticosteroids to the lungs

Pulmonary delivery is the preferred route of drug administration in the treatment of many respiratory disease, such as asthma and chronic obstructive pulmonary disease (COPD). Over the years, several kinds of carriers have been studied for sustained release of corticosteroids and bronchodilators to the lungs. Solid Lipid Microparticles (SLM) due to their biocompatibility and size (3-5 µm) can reach the bronchial epithelium directly, circumvent first pass metabolism and avoid systemic toxicity [1,2]. In this work we describe the preparation and the characterization of two different systems subjected to chitosan and alginate coating for sustained release of fluticasone propionate (FP) into th…

Phospholipid-polyaspartamide micelles for pulmonary delivery of corticosteroids

A novel drug delivery system for beclomethasone dipropionate (BDP) has been constructed through self-assembly of a pegylated phospholipid-polyaminoacid conjugate. This copolymer was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)2000] (DSPE-PEG(2000)-NH(2)). Benefiting from the amphiphilic structure with the hydrophilic shell based on both PHEA and PEG and many hydrophobic stearoyl tails, PHEA-PEG(2000)-DSPE copolymer was able to self assemble into micelles in aqueous media above a concentration of 1.23 × 10(-7)M, determined by fluorescence studies. During the self-assembling …

ChemInform Abstract: Further Furoclerodanes from Teucrium “maghrebinum”

Two more pairs of C-12 epimeric neoclerodanes were isolated from the aerial parts of Teucrium “maghrebinum” (Teucriumpolium subspecies still unidentified). They are the known teukotschyn 1, the new 12-epi-teukotschyn 2, the new teughrebin 3 and the new 12-epi-teughrebin 4. The structures of the new products were elucidated mainly by spectroscopic methods.

Neoclerodane Diterpenoids from Teucrium maghrebinum

Eight neoclerodane diterpenoids were identified in the extract of the aerial parts of Teucrium maghrebinum. Three of these, 12-epi-teucjaponin A (1), 12-epi-montanin D (2), and 12-epi-montanin B (3), are new natural products, whereas five, teucjaponin A, montanin D, 19-deacetylteuscorodol, teusalvin C (4), and montanin B, are already known. These eight compounds form four pairs of epimers at carbon C-12.

Supramolecular Assemblies Based on Complexes of Nonionic Amphiphilic Cyclodextrins and a meso-Tetra(4- sulfonatophenyl)porphine Tributyltin(IV) Derivative: Potential Nanotherapeutics against Melanoma

Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors by modulating the balance between the hydrophobic and hydrophilic chains at both CyD sides. This work aimed to design nanoassemblies based on nonionic and hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the porphyrin derivatives under simulated physiological conditions, a speciation was performed using complementary techniques. In aqueous solution (≤ 20 μM), (Bu3Sn)4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the low static anisotropy (ρ ≈ 0.02) with a negligible formation of por…

Nanoassemblies Based on Supramolecular Complexes of Nonionic Amphiphilic Cyclodextrin and Sorafenib as Effective Weapons to Kill Human HCC Cells

Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HOC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and H-1 NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role…

Biocompatible Lipid Nanoparticles as Carriers to Improve Curcumin Efficacy in Ovarian Cancer Treatment

Curcumin is a natural molecule with proved anticancer efficacy on several human cancer cell lines. However, its clinical application has been limited due to its poor bioavailability. Nanocarrier-based drug delivery approaches could make curcumin dispersible in aqueous media, thus overtaking the limits of its low solubility. The aim of this study was to increase the bioavailability and the antitumoral activity of curcumin, by entrapping it into nanostructured lipid carriers (NLCs). For this purpose here we describe the preparation and characterization of three kinds of curcumin-loaded NLCs. The nanosystems allowed the achievement of a controlled release of curcumin, the amounts of curcumin r…

Lipid nanocarriers containing sorafenib inhibit colonies formation in human hepatocarcinoma cells

Here, the potential of two nanostructured lipid carriers (NLC) for controlled release of sorafenib was evaluated. The obtained systems showed characteristics suitable as drug delivery systems for the treatment of hepatocellular carcinoma (HCC) through parenteral administration. The use of a mixture between a solid lipid (tripalmitin) with a liquid lipid (Captex 355 EP/NF or Miglyol 812) to prepare NLC systems could give a higher drug loading capacity and a longer term stability during storage than that obtained by using only solid lipids. The obtained nanoparticles showed a nanometer size and high negative zeta potential values. Scansion electron microscopy (SEM) of the sorafenib loaded NLC…

Nanostructured Lipid Carriers-Containing Anticancer Compounds: Preparation, Characterization, and Cytotoxicity Studies

This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particula…

NOVEL COMPOSED GALACTOSYLATED NANODEVICES CONTAINING A RIBAVIRIN PRODRUG AS HEPATIC CELL-TARGETED CARRIERS FOR HCV TREATMENT

In this paper, we describe the preparation of liver-targeted nanoparticles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes). These particles were obtained starting from a galactosylated phospholipid-polyaminoacid conjugate. This latter was obtained by chemical reaction of ALPHA, BETA -poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydroph…

Minor diterpenoids from Scutellaria polyodon.

Four minor neoclerodane diterpene constituents were isolated from the aerial parts of Scutellaria polyodon. These compounds were characterized as the new scupolins J (1) and K (2) and the previously known scutalpin O (3) and scutalsin.

Minimalism in radiation synthesis of biomedical functional nanogels.

A scalable, single-step, synthetic approach for the manufacture of biocompatible, functionalized micro- and nanogels is presented. In particular, poly(N-vinyl pyrrolidone)-grafted-(aminopropyl)methacrylamide microgels and nanogels were generated through e-beam irradiation of PVP aqueous solutions in the presence of a primary amino-group-carrying monomer. Particles with different hydrodynamic diameters and surface charge densities were obtained at the variance of the irradiation conditions. Chemical structure was investigated by different spectroscopic techniques. Fluorescent variants were generated through fluorescein isothiocyanate attachment to the primary amino groups grafted to PVP, to …

Nanotechnology applications for the therapy of liver fibrosis.

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and, in the more advanced stages, for the limited available curative treatment options. In fact, when lesions of different etiologies chronically affect the liver, triggering the fibrogenesis mechanisms, damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications, expensive treatments and death in end-stage liver disease. Despite significant advances in the understanding of the mechanisms of liver fibrinogenesis, the drugs used in liver fibrosis treatment still have a limited therapeutic effect. Many drugs showing potent ant…

Salmeterol Xinafoate (SX) loaded into mucoadhesive solid lipid microparticles for COPD treatment

Chronic obstructive pulmonary disease (COPD) is one of the main health problems worldwide. It is characterised by chronic inflammation in the lungs that leads to progressive, chronic, largely irreversible airflow obstruction. The use of long-acting β agonists remain today the frontline treatment for COPD with the aim of minimizing side effects and enhancing therapeutic usefulness. To this purpose, in this paper, mucoadhesive solid lipid microparticles (SLMs) containing a long-acting β-2 agonist, Salmeterol Xinafoate (SX) were prepared, characterised (size, z-potential, aerodynamic diameter, turbidimetric evaluations, drug loading and entrapping efficiency) and tested in a model of bronchial…

Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2

Maria Luisa Bondì1,*, Giovanna Montana2,*, Emanuela Fabiola Craparo3, Roberto Di Gesù3, Gaetano Giammona3, Angela Bonura2, Paolo Colombo21Istituto per lo Studio dei Materiali Nanostrutturati, 2Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, 3Laboratory of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari Stembio, Università di Palermo, Palermo, Italy *These authors contributed equally to this workAbstract: Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specific immunotherapy is the only…

Structure and biological evaluation of amino-functionalized PVP nanogels for fast cellular internalization

Abstract Aminopropyl methacrylamide chloride-graft-poly(N-vinyl pyrrolidone) nanogels (NGs) were designed to exploit the favorable properties of poly(N-vinyl pyrrolidone) (PVP), such as its high affinity to water and complexation ability of ions, molecules and macromolecules, with the availability of primary amino groups for bioconjugation reactions. A thorough structural characterization of the nanoscalar networks was performed via 1 H NMR and solid state 13 C NMR spectroscopies, while solid state NMR relaxation time measurements completed the NGs description in terms of polymer network density. Information on the hydrodynamic size and surface charge densities were sought via dynamic light…

Solid Lipid Nanoparticles Containing Nimesulide: Preparation, Characterization and Cytotoxicity Studies

The prospect of improved cancer therapy using Solid Lipid Nanoparticles (SLNs) as drug delivery system is promising. Sev- eral 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 per- formance by inducing accumulation into tumours by enhanced permeability and retention (EPR) effect. This paper deals with the devel- opment of SLN containing nimesulide, a non-steroidal anti-inflammatory drug with antitumour effect and low solubility in water. Here, SLNs carrying nimesulide were prepared…

NANOPARTICLES BASED ON NOVEL AMPHIPHILIC POLYASPARTAMIDE COPOLYMERS

In this article, the synthesis of two amphiphilic polyaspartamide copolymers, useful to obtain polymeric nanoparticles without using surfactants or stabilizing agents, is described. These copolymers were obtained starting from α,β-poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA) by following a novel synthetic strategy. In particular, PHEA and its pegylated derivative (PHEA-PEG2000) were functionalized with poly(lactic acid) (PLA) through 1,1′-carbonyldiimidazole (CDI) activation to obtain PHEA–PLA and PHEA-PEG2000–PLA graft copolymers, respectively. These copolymers were properly purified and characterized by 1H-NMR, FT-IR, and Size Exclusion Chromatography (SEC) analyses, which confirmed that…

Further Furoclerodanes fromTeucrium “maghrebinum”

Two more pairs of C-12 epimeric neoclerodanes were isolated from the aerial parts of Teucrium “maghrebinum” (Teucriumpolium subspecies still unidentified). They are the known teukotschyn 1, the new 12-epi-teukotschyn 2, the new teughrebin 3 and the new 12-epi-teughrebin 4. The structures of the new products were elucidated mainly by spectroscopic methods.

Neoclerodane Diterpenoids from Scutellaria polyodon

Nine new neoclerodane diterpenoids, scupolins A−I, have been isolated from an Me2CO extract of the aerial parts of Scutellaria polyodon (3−11), together with the known neoclerodanes jodrellin B (1) and scutecolumnin A (2). Structures 3−11 were established by spectroscopic means and by comparison with closely related compounds.

EMPLOYMENT OF CATIONIC SOLID-LIPID NANOPARTICLES AS RNA CARRIERS

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. In this article, the suitability of cationically modified solid-lipid nanoparticles (SLN) as a nonviral vector for gene delivery was investigated, in order to obtain stable materials able to condense RNA. Cationic SLN were produced by microemulsion using Compritol ATO 888 as matrix lipid, Pluronic F68 as tenside, and dimethyldioctadecylammonium bromide (DDAB) as cationic lipid. The resulting particles were approximately 100 nm in size and showed a highly positive surface charge (+41 mV) in water. Size and shape were further characterized by scanning electron microscopy (SEM) measurements. M…

Ferulic Acid-Loaded Lipid Nanostructures as Drug Delivery Systems for Alzheimers Disease: Preparation, Characterization and Cytotoxicity Studies

High-energy radiation processing, a smart approach to obtain PVP-graft-AA nanogels

Abstract Poly(N-vinylpyrrolidone)-grafted-acrylic acid biocompatible nanogels (NGs) were prepared using an exiting industrial-type electron accelerator and setups, starting from semi-dilute aqueous solutions of a commercial PVP and the acrylic acid monomer. As a result, NGs with tunable size and structure can be obtained quantitatively. Sterility was also imparted at the integrated dose absorbed. The chemical structure of the NGs produced was confirmed through Fourier Transformer Infrared Spectroscopy (FT-IR). The molecular and physico-chemical properties of NGs, such as the hydrodynamic dimensions and surface charge densities, for various polymer and monomer concentrations in the irradiate…

Large-scale radiation manufacturing of hierarchically assembled nanogels

Nanogels (NGs), or small particles formed by physically or chemically crosslinked polymer networks, represent a niche in the development of "smart" nanoparticles for drug delivery and diagnostics. They offer unique advantages over other systems, including a large and flexible surface for multivalent bio-conjugation; an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs; the possibility to entrap active metal or mineral cores for imaging or phototherapeutic purposes; stimuli-responsiveness to achieve temporal and/or site control of the release function and biocompatibility. The availability of inexpensive and robust preparation methodologies is at the ba…

Curcumin entrapped into lipid nanosystems inhibits neuroblastoma cancer cell growth and activates Hsp70 protein

Curcumin is a natural anti-cancer compound utilized on a wide variety of human cancer cell lines and animal carcinogenesis models. However, its clinical application has been limited for its minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic molecules such as curcumin dispersible in aqueous media, thus overtaking the limits of its poor solubility. In this paper, we reported the preparation and chemical-physical characterization of Nanostructured Lipid Carriers (NLC) containing curcumin, based on Imwitor, Compritol or Precirol as lipid matrix. By in vitro experiments, we have demonstrated that these nano-systems are able …

A Nanoparticulate Drug-Delivery System for Rivastigmine: Physico-Chemical and in vitro Biological Characterization

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG 2000 as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG 2000 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 pH = 7.4 and human plasma.

Polyaspartamide-based nanoparticles loaded with fluticasone propionate and the in vitro evaluation towards cigarette smoke effects

This paper describes the evaluation of polymeric nanoparticles (NPs) as a potential carrier for lung administration of fluticasone propionate (FP). The chosen polymeric material to produce NPs was a copolymer based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) whose backbone was derivatised with different molecules, such as poly(lactic acid) (PLA) and polyethylenglycol (PEG). The chosen method to produce NPs from PHEA-PLA-PEG2000 was the method based on high-pressure homogenization and subsequent solvent evaporation by adding Pluronic F68 during the process and trehalose before lyophilisation. Obtained colloidal FP-loaded NPs showed a slightly negative surface charge and nanometric d…

BRAIN-TARGETED SOLID LIPID NANOPARTICLES CONTAINING RILUZOLE: PREPARATION, CHARACTERIZATION AND BIODISTRIBUTION

Aim: Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Materials & method: Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodi…

Synthesis and self-assembly of a PEGylated-graphene aerogel

Abstract In the frame of this work, we present, for the first time, the synthesis and self-assembly of an aerogel built by graphene oxide-polyethylene glycol. The synthetic route involves at first the coupling of GO with an amino-terminated polyethylene glycol sample by carbodiimide in aqueous environment, and the subsequent conversion of the hydrogel achieved into an aerogel via freeze-drying. The 3D PEGylated graphene-based aerogel, characterized by spectroscopic, morphological, structural and mechanical analyses, displays an ultralight and highly porous (99.7%) network and possesses high mechanical properties together with a good biocompatibility.

Evaluation of biodegradability on polyaspartamide-polylactic acid based nanoparticles by chemical hydrolysis studies

Here, the synthesis of two graft copolymers based on ?,?-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and poly(lactic acid) (PLA), the O-(2-aminoethyl)-O'-galactosyl polyethylene glycol (GAL-PEG-NH2) or the methoxypolyethylene glycol amine (H2N-PEG-OCH3) is described. Starting from the obtained PHEA-PLA-PEG-GAL and PHEA-PLA-PEG copolymers, polymeric nanoparticles were prepared by high pressure homogenization-solvent evaporation method. To demonstrate their biodegradability as a function of the matrix composition, a chemical stability study was carried out until 21 days by incubating systems in two media mimicking physiological compartments (pH 7.4 and pH 5.5). The degradability of both nan…

Pegylated nanoparticles based on a polyaspartamide. Preparation, physico-chemical characterization and intracellular uptake

Nanoparticles with different surface PEGylation degree were prepared by using as starting material alpha,beta-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA). PHEA was functionalized with a PEG amino-derivative for obtaining PHEA-PEG(2000) copolymer. Both PHEA and PHEA-PEG(2000) were derivatized with methacrylic anhydride (MA) for obtaining poly(hydroxyethylaspartamide methacrylated) (PHM) and poly(hydroxyethylaspartamide methacrylated)-PEGylated (PHM-PEG(2000)), respectively. Nanoparticles were obtained by UV irradiation of an inverse microemulsion, using as internal phase an aqueous solution of PHM alone or of the PHM/PHM-PEG(2000) mixture at different weight ratio and as external phase a m…

An ent-kaurane from Sideritis huber-morathii

WOS: A1996VW86500030

Novel cationic solid-lipid nanoparticles as non-viral vectors for gene delivery.

In this paper, the suitability of novel cationic solid-lipid nanoparticles (SLN) as a nonviral transfection agent for gene delivery was investigated. SLN were produced by using the microemulsion method and Compritol ATO 888 as matrix lipid, dimethyldioctadecylammonium bromide as charge carrier and Pluronic F68 as surfactant. Obtained nanoparticles were approximately 120 nm in size and positively charged, with a zeta potential value equal to +45 mV in twice-distilled water. Cationic SLN were able to form stable complexes with DNA and to protect DNA against DNase I digestion. The SLN-DNA complexes were characterized by mean diameter and zeta potential measurements. In vitro studies on human l…

Effects in cigarette smoke stimulated bronchial epithelial cells of a corticosteroid entrapped into nanostructured lipid carriers

Background Nanomedicine studies have showed a great potential for drug delivery into the lung. In this manuscript nanostructured lipid carriers (NLC) containing Fluticasone propionate (FP) were prepared and their biocompatibility and effects in a human bronchial epithelial cell line (16-HBE) stimulated with cigarette smoke extracts (CSE) were tested. Results Biocompatibility studies showed that the NLC did not induce cell necrosis or apoptosis. Moreover, it was confirmed that CSE increased intracellular ROS production and TLR4 expression in bronchial epithelial cells and that FP-loaded NLC were more effective than free drug in modulating these processes. Finally, the nanoparticles increased…

An allergen-polymeric nanoaggregate as a new tool for allergy vaccination.

Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specifi immunotherapy is the only treatment able to modify the natural outcome of the disease by restoring a normal immunity against allergens. The preparation of allergen-solid lipid nanoparticles as delivery vehicles for therapeutic proteins, P. judaica major allergen Par j 2, was investigated. The Par j 2 allergen was expressed in a large amount in Escherichia coli and purifid to homogeneity. Its immunological properties were studied by western blotting and enzyme-linked immunosorbent assay inhibition. Solid lipid nanoparticles were obtained by …

Surfactant effect on the physicochemical characteristics of cationic solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) may be considered as a new approach for therapeutics for many diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be obtained by including cationic lipids, which provide a positive surface potential that favors binding to the nucleic acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is indispensable for obtaining nanoparticles with surface positive charge. In this study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide, cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN usi…

Application of polymeric nanoparticles in immunotherapy.

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. Polyme…

Mucoadhesive solid lipid microparticles for controlled release of a corticosteroid in the chronic obstructive pulmonary disease treatment.

Therapeutic efficacy of inhaled drugs is limited by rapid clearance from the site of action due to absorption into systemic circulation or metabolic degradation by alveolar macrophages. Drug delivery systems offer new solutions to clinical problems especially in the treatment of pulmonary diseases. In particular, Solid Lipid Microparticles (SLM) in the range of 3-5 µm are suggested as systems for delivery of therapeutics to the lung as, because of their size, they are able to deposit into secondary bronchi, avoiding systemic absorption typical of alveolar regions. Here, we describe two novel different SLMs prepared with chitosan and alginate for sustained release of fluticasone propionate (…

Oligonucleotides-decorated-poly(N-vinyl pyrrolidone) nanogels for gene delivery

Pulsed electron-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a sing…

Guaianolides and other terpenoids from Anthemis aetnensis

Aerial parts of Anthemis aetnensis furnished the guaianolides hydruntinolide A and B and a number of new analogues, two new germacradienolides, 1-β-hydroxyarbusculin and the isofraxidin derived sesquiterpene ether 7-acetoxypectanone.

Lipid Nanoparticles for Drug Targeting to the Brain

In this chapter, the main production methods of lipid nanostructures such as solid lipid nanoparticles and nanostructured lipid carriers, and their application are described. In particular, we describe the strategies commonly used to obtain lipid nanoparticles to overcome the blood-brain barrier (BBB) for the treatment of several brain diseases. The use of these carriers as targeted drug delivery systems is associated with many advantages that include excellent storage stability, easy production without the use of any organic solvent, the possibility of steam sterilization and lyophilization, and large scale production. They exhibit good stability during long-term storage, consist of physio…

Nanoparticulate Systems for Drug Delivery and Targeting to the Central Nervous System

Brain delivery is one of the major challenges for the neuropharmaceutical industry 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 central nervous system (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. Many recent data demonstrate that drugs could be transported successfully into the brain using colloidal systems after i.v. injection by several mechanisms such as endocytosis or P-glycoprotei…

Neo-clerodane diterpenoids from Scutellaria lateriflora

Abstract Three new diterpenoids, scutelaterins A-C, have been isolated from Scutellaria lateriflora and their structures established as (11S,13S,16S)-2β,6α,19-triacetoxy-4α,18;11,16;15,16-triepoxy-neo-clerod-14-ene (scutelaterin A), (11S,13S,16S)-6α,19-diacetoxy-2β-(2′-methyl)butyryloxy-4α,18;11,16;15,16-triepoxy-neo-clerod-14-ene (scutelaterin B) and (11S,13S,15R and S)-6α,19-diacetoxy-2β-(2′-methyl)butyryloxy-4α,18;11,16;15,16-triepoxy-neo-clerodan-15-ol (scutelaterin C) by chemical and spectroscopic means. In addition, the already known neo-clerodanes ajugapitin and scutecyprol A were also found in the same source.