Baclofen-loaded solid lipid nanoparticles: preparation, electrophysiological assessment of efficacy, pharmacokinetic and tissue distribution in rats after intraperitoneal administration.

Intrathecal baclofen administration is the reference treatment for spasticity of spinal or cerebral origin, but the risk of infection or catheter dysfunctions are important limits. To explore the possibility of alternative administration routes, we studied a new preparation comprising solid lipid nanoparticles (SLN) incorporating baclofen (baclofen-SLN). We used SLN because they are able to give a sustained release and to target the CNS.

Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants.

Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage.

Melatonin is a potent antioxidant molecule with a capacity to protect tissues from damage caused by oxidative stress. It reduces cyclosporine A (CsA)-induced cardiotoxicity; this improvement required melatonin's binding to its membrane receptors. This experimental study examined whether melatonin is a useful tool for counteracting CsA-induced apoptosis in the heart of rats.

Chapter 11 - Solid lipid nanoparticles for brain tumors therapy: State of the art and novel challenges.

Malignant gliomas, despite aggressive multimodal therapies and adequate supportive care, still maintain poor prognosis. Solid lipid nanoparticles (SLN) are colloidal carriers that could be regarded as a highly flexible platform for brain tumor imaging and therapeutical purposes. In this chapter we will first describe brain tumors characteristics and conventional therapeutical approaches.

Chapter 10 - Solid lipid nanoparticles and microemulsions for drug delivery The CNS.

The chapter examined solid lipid nanoparticles (SLN) and microemulsions, chosen as carriers of drugs, administered in vivo to be transported to the central nervous system. Drugs of different structures and for different therapies have been studied such as doxorubicin SLN stealth and nonstealth administered in rats by intravenous route, apomorphine SLN administered in rats by duodenal route, melatonin SLN administered by transdermal and oral routes in humans, and apomorphine microemulsion administered by transdermal route in Parkinson's patients. The pharmacokinetics of the drug, followed in most studies, put in evidence that the many important pharmacokinetic parameters were notably improved versus the drug alone or in a commercial formulation.

Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems.

melatonin (MT) is a hormone produced by the pineal gland at night, involved in the regulation of circadian rhythms. For clinical purposes, exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable due to short half-life of elimination. Aim of this study is to examine pharmacokinetics of MT incorporated in solid lipid nanoparticles (SLN), administered by oral and transdermal route.

Cholesterylbutyrate solid lipid nanoparticles as a butyric acid prodrug.

Cholesterylbutyrate (Chol-but) was chosen as a prodrug of butyric acid. Butyrate is not often used in vivo because its half-life is very short and therefore too large amounts of the drug would be necessary for its efficacy. In the last few years butyric acid's anti-inflammatory properties and its inhibitory activity towards histone deacetylases have been widely studied, mainly in vitro.

Nanovector.

Nanovector was founded in 2001 and is one of the companies that first began working in the nanomedicine field in Italy, having a specific focus on developing its technical platform for drug-delivery applications. Proprietary lipid nanocarriers, microemulsions and Solid Lipid Nanoparticles have been tested over recent years, delivering different drugs by different administration routes: in this profile, a short overview of our main results will be given. The delivery system platform has shown and confirmed promising characteristics.

Solid lipid nanoparticles: could they help to improve the efficacy of pharmacologic treatments for brain tumors?

Objectives: Brain malignant neoplasms are still characterized by poor prognosis due to their peculiar hallmarks that severely limit aggressive multimodal therapeutic approaches. The optimization of the intratumoral drug delivery, directed to achieve effective concentrations and to reduce systemic undesired toxicity, is one of the primary goals of the brain tumors therapeutic strategies. Different passive and active delivery carriers allowing to a better control of drug distribution, metabolism, and elimination after parenteral administration have been developed.

Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines.

The structure of both carrier and anticancer drug affects the intracellular fate of a transported drug. The study investigated in vitro intracellular accumulation and cytotoxic activity of doxorubicin-loaded solid lipid nanoparticles (SLN), doxorubicin in pegylated liposomes (Caelyx) and free doxorubicin. Intracellular doxorubicin levels and cytotoxic activity were determined by high performance liquid chromatography with fluorescence detection, and by the trypan blue dye exclusion assay, respectively.

Transdermal treatment options for neurological disorders: impact on the elderly.

As people grow old, their need for medications increases dramatically because of the higher incidence of chronic pain, diabetes mellitus, cardiovascular and neurological diseases in the elderly population. Furthermore, the elderly require special consideration with respect to drug delivery, drug interactions and adherence. In particular, patients with chronic neurological diseases often require multiple administration of drugs during the day to maintain constant plasma medication levels, which in turn increases the likelihood of poor adherence.

Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells.

1. Adhesion of polymorphonuclear cells (PMNs) to vascular endothelial cells (EC) is a critical step in recruitment and infiltration of leukocytes into tissues during inflammation. High doses of butyric acid have been shown to ameliorate inflammation in inflammatory bowel diseases (IBD).

Transdermal apomorphine permeation from microemulsions: a new treatment in Parkinson's disease.

We studied absorption, efficacy, and tolerability in Parkinson's disease (PD) of a new preparation of apomorphine included in a microemulsion and administered by transdermal route (Apo-MTD). Twenty-one PD patients were treated with levodopa plus oral dopamine-agonists (T0), with levodopa alone (T1), finally with levodopa plus Apo-MTD (T2). Apo-MTD provided therapeutic plasma levels for many hours, improved Unified Parkinson's Disease Rating Scale III scores, and reduced total duration of off periods compared to T0 and T1.

Cholesteryl butyrate solid lipid nanoparticles as a butyric acid pro-drug: effects on cell proliferation, cell-cycle distribution and c-myc expression in human leukemic cells.

Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed as a pro-drug to deliver butyric acid. We compared the effects on cell growth, cell-cycle distribution and c-myc expression of chol-but SLN and sodium butyrate (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell lines 0.

Scale-up and optimization of an evaporative drying process applied to aqueous dispersions of solid lipid nanoparticles.

An apparatus to dry aqueous dispersions of solid lipid nanoparticles (SLNs) was designed. Optimal running conditions were evaluated to obtain minimum process time and produce dried SLNs characterized by small size variation. To achieve process optimization, SLN average diameter, SLNs polydispersity index, and drying time were related to three operative variables: process temperature, SLN concentration in the original aqueous dispersions, and nitrogen flow rate as the physical means of the drying process.

In vitro and in vivo study of solid lipid nanoparticles loaded with superparamagnetic iron oxide.

Solid Lipid Nanoparticles (SLN) are already under investigation as a pharmaceutical tool able to change the pharmacokinetic and biodistribution of carried molecules. SLN are able to target drugs to lymph after duodenal administration and to overcome the Blood Brain Barrier (BBB). In this study, superparamagnetic SLN have been prepared, have colloidal size, in vitro analysis showed relaxometric properties similar to Endorem.

Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin.

Three types of solid lipid nanoparticles (SLN) containing three different percentages of tobramycin (1.25, 2.50, 5.

Intravenous administration to rabbits of non-stealth and stealth doxorubicin-loaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other tissues.

The pharmacokinetics and tissue distribution of doxorubicin incorporated in non-stealth solid lipid nanoparticles (SLN) and in stealth solid lipid nanoparticles (SSLN) (three formulations at increasing concentrations of stearic acid-PEG 2000 as stealth agent) after intravenous administration to conscious rabbits have been studied. The control was the commercial doxorubicin solution. The experiments lasted 6 h and blood samples were collected at fixed times after the injections.

Incorporation of cyclosporin A in solid lipid nanoparticles (SLN).

The cyclic undecapeptide cyclosporin A (CyA) a potent immunosuppressive drug used in many therapies, is extremely hydrophobic. Commercial products employ solubilising agents to improve gastrointestinal absorption. In the present study CyA solid lipid nanoparticles (SLN) are prepared from warm o/w microemulsion, dispersed in cold water.

Pharmacokinetics and tissue distribution of idarubicin-loaded solid lipid nanoparticles after duodenal administration to rats.

Idarubicin-loaded solid lipid nanoparticles (IDA-SLN) and idarubicin in solution were prepared and the two formulations were administered to rats, either by the duodenal route or intravenously (iv). The aim of this research was to study whether the bioavailability of idarubicin can be improved by administering IDA-SLN duodenally to rats. Idarubicin and its main metabolite idarubicinol were determined in plasma and tissues by reversed-phase high-performance liquid chromatography.