103 research outputs found
α-Acylamino-β-lactone N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors Encapsulated in PLGA Nanoparticles: Improvement of the Physical Stability and Protection of Human Cells from Hydrogen Peroxide-Induced Oxidative Stress
No full textN-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that preferentially catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide, which has been shown to exhibit neuroprotective and antinociceptive properties by engaging peroxisome proliferator-activated receptor-α. A few potent NAAA inhibitors have been developed, including α-acylamino-β-lactone derivatives, which are very strong and effective, but they have limited chemical and plasmatic stability, compromising their use as systemic agents. In the present study, as an example of a molecule belonging to the chemical class of N-(2-oxo-3-oxetanyl)amide NAAA inhibitors, URB866 was entrapped in poly(lactic-co-glycolic acid) nanoparticles in order to increase its physical stability. The data show a monomodal pattern and a significant time- and temperature-dependent stability of the molecule-loaded nanoparticles, which also demonstrated a greater ability to effectively retain the compound. The nanoparticles improved the photostability of URB866 with respect to that of the free molecule and displayed a better antioxidant profile on various cell lines at the molecule concentration of 25 μM. Overall, these results prove that the use of polymeric nanoparticles could be a useful strategy for overcoming the instability of α-acylamino-β-lactone NAAA inhibitors, allowing the maintenance of their characteristics and activity for a longer time
Supramolecular devices to improve the treatment of brain diseases
No full textThe blood-brain barrier (BBB) hinders the accumulation of active compounds in the central nervous system, thus decreasing their therapeutic effectiveness. To overcome this obstacle, interesting supramolecular nanodevices are herein considered. These systems have many advantages over the conventional formulations, such as having structures made up of biocompatible and biodegradable materials, the possibility of bypassing the BBB in a non-invasive manner (without structural modifications) and the possibility of being structurally modified to modulate the biopharmaceutical properties of the encapsulated compounds. Polymolecular (liposomes, niosomes, nanogels) and oligomolecular (cyclodextrins) devices have potential clinical applications in brain drug delivery, being capable of active targeting that can concentrate bioactives in the brain
Ethosomes® and transfersomes® containing linoleic acid: physicochemical and technological features of topical drug delivery carriers for the potential treatment of melasma disorders
No full textTwo vesicular colloidal carriers, ethosomesA (R) and transfersomesA (R) were proposed for the topical delivery of linoleic acid, an active compound used in the therapeutic treatment of hyperpigmentation disorders, i.e. melasma, which is characterized by an increase of the melanin production in the epidermis. Dynamic light scattering was used for the physicochemical characterization of vesicles and mean size, size distribution and zeta potential were evaluated. The stability of formulations was also evaluated using the Turbiscan LabA (R) Expert based on the analysis of sample transmittance and photon backscattering. EthosomesA (R) and transfersomesA (R) were prepared using Phospholipon 100 GA (R), as the lecithin component, and ethanol and sodium cholate, as edge activator agents, respectively. Linoleic acid at 0.05% and 0.1% (w/v) was used as the active ingredient and entrapped in colloidal vesicles. Technological parameters, i.e. entrapment efficacy, drug release and permeation profiles, were also investigated. Experimental findings showed that physicochemical and technological features of ethosomesA (R) and transfersomesA (R) were influenced by the lipid composition of the carriers. The percutaneous permeation experiments of linoleic acid-loaded ethosomesA (R) and transfersomesA (R) through human stratum corneum-epidermidis membranes showed that both carriers are accumulated in the skin membrane model as a function of their lipid compositions. The findings reported in this investigation showed that both vesicular carriers could represent a potential system for the topical treatment of hyperpigmentation disorders
Characterization and Preliminary In Vitro Antioxidant Activity of a New Multidrug Formulation Based on the Co-Encapsulation of Rutin and the α-Acylamino-β-Lactone NAAA Inhibitor URB894 within PLGA Nanoparticles
No full textA biodegradable and biocompatible polymeric matrix made up of poly(d,l-lactide-co-glycolide) (PLGA) was used for the simultaneous delivery of rutin and the (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide derivative (URB894). The goal was to exploit the well-known radical scavenging properties of rutin and the antioxidant features recently reported for the molecules belonging to the class of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors, such as URB894. The use of the compounds, both as single agents or in association promoted the development of negatively-charged nanosystems characterized by a narrow size distribution and an average diameter of ~200 nm when 0.2–0.6 mg/mL of rutin or URB894 were used. The obtained multidrug carriers evidenced an entrapment efficiency of ~50% and 40% when 0.4 and 0.6 mg/mL of rutin and URB894 were associated during the sample preparation, respectively. The multidrug formulation evidenced an improved in vitro dose-dependent protective effect against H2O2-related oxidative stress with respect to that of the nanosystems containing the active compounds as a single agent, confirming the rationale of using the co-encapsulation approach to obtain a novel antioxidant nanomedicine
Post-insertion parameters of PEG-derivatives in phosphocholine-liposomes
No full textThe insertion of specific derivatives into pre-formed colloidal systems has been shown to be a useful method for modifying their pharmacokinetic characteristics and biodistribution profiles. In this experimental work the effect of the post-insertion of different PEG-derivatives into pre-formed 100-nm liposomes made up of various lipid mixtures (DMPC, DPPC, DOPC, DSPC and cholesterol at different molar ratios) was investigated. The vesicles were incubated with increasing amounts of DSPE-mPEG2000 as sterically stabilized micelles (5, 10 and 15% w/w with respect to the liposomal lipid mixture) in order to favour the insertion of the PEG-lipid into the liposomal bilayer. The colloidal formulations were characterized by photo-correlation spectroscopy; the DSPE-mPEG2000 integrated into the pre-formed liposomes was demonstrated by means of field flow fractionation while the amount of post-inserted compound was quantified using a suitable spectrophotometric assay (I2 assay). Similar investigations have been performed using PEG-derivatives characterized by a different molecular weight. The physico-chemical properties of the various liposomal formulations were influenced by the post-insertion of PEG-derivatives. The lipid mixture made up of saturated phospholipids and cholesterol proved to be the best, post-insertion (P.I.E.). The post-insertion technique may be a suitable approach to be used in personalized (nano)medicine
PHARMACOKINETICS OF GEMCITABINE HYDROCHLORIDE AND IRINOTECAN HYDROCHLORIDE ALONE AND IN COMBINATION IN RAT PLASMA BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-DIODE ARRAY DETECTOR
No full textThis communication reports an easy and quick HPLC-PDA method for the simultaneous analysis of Irinotecan Hydrochloride and Gemcitabine Hydrochloride in rat plasma samples both after single drug administration and drugs association. Gemcitabine Hydrochloride is commonly administered to treat non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma, and in combination with paclitaxel for the treatment of breast cancer in the metastatic phase. Additionally Irinotecan Hydrochloride was used to treat colorectal cancer (CRC), gynecological cancers, carcinomas, non-small cell and small cell lung cancer. The drugs were detected simultaneously by using a Zorbax Extend C-18 column (250 mm × 4.6 mm; 5 m particle size) in gradient elution mode. The chromatographic analysis was performed in 15 minutes. The analytical method was calibrated and validated from 0.1 to 18 g/mL for both drugs. Rat plasma was used as biological samples during the analysis; while the 3-methylxanthine was used as internal standard. The performance of analytical method was further tested in rat plasma samples collected after single dose administration of drug or their association. Results demonstrated that HPLC-PDA method allows to detect the drugs in the range of concentrations herein reported and the analytical method is accurate and selective. The limit of quantification of the method was 0.1 g/mL. These values are similar or little higher to data published in literature, which are performed using sophisticated and expensive detectors such as mass spectrometer, and wich consider merely only one drug and not their association. The weighted-matrix matched standard curves showed a good linearity until 18 g/mL. The parallelism tests were also performed to evaluate if over-range samples can be analyzed after dilution, without affecting the performance of validated method. The intra- and inter-day precision (RSD%) values were ≤7.14% and ≤11.5%, respectively, for the full range of analysis. The intra- and inter-day trueness (Bias%) values ranged from -11.5% to 1.70% for the two drugs. At the best of our knowledge, this is the first HPLC-PDA method which allows to detect simultaneously Irinotecan Hydrochloride and Gemcitabine Hydrochloride in rat plasma, both after single and drugs association administration in order to evaluate how can interact and modify the pharmacokinetic parameters.
[1] M. Locatelli et. al. Simultaneous determination of Gemcitabine Hydrochloride and Irinotecan Hydrochloride in rat plasma by high performance liquid chromatography-diode array detector. J. Pharm. Biomed. Anal., Submitted (2018
Nanostructured Lipid Carriers (NLC) for the topical delivery of lutein
No full textLutein is a natural carotenoid with antioxidant properties, already proven in various topical applications. A 20% suspension of lutein in safflower oil (FloraGLO®Lutein) represents a good raw material for the production of creams and other semisolid formulations. However, the high viscosity of FloraGLO® and poor chemical stability of lutein in the suspension represents a practical limitation to its use. An efficient method was proposed in this study for taking benefit of the liquid oily composition of FloraGLO®, by realizing a nanostructured carrier system (NLC) able to ensure a controlled release of lutein and improve its permeability across the skin. NLC were prepared with different percentages of FloraGLO® as the liquid phase of NLC. The physical stability of NLC was assessed by storage at room conditions and by Turbiscan accelerated analysis. All the produced nanocarriers were perfectly tolerated after application on the skin. In an in vivo model of UV-induced skin erythema, the lutein-loaded NLC were able to improve the photo-protective effects of the antioxidant compared to the commercial suspension, when the NLC formulations were applied before inducing the erythema. This study also proved for the first time the possibility of converting a liquid formulation into a solid, modified release nanocarrier with more manageable formulative features
LIPOSOMAL SYSTEM WITH KILLER TNF-APOPTOSIS INDUCED LIGAND (KILLERTRAIL), PRO-APOPTOTIC-DIRECTING
No full textThe present invention relates to the development of transport systems of the liposomal type which have PEGylated compounds conjugated with derivatives of the family of Tumor Necrosis Factor cytokines on the surface of the vesicular structure. The conjugation strategy is to bind the protein, preferably TRAIL, more preferably KillerTRAIL, in monomeric form, to the polyethylene glycol (PEG) via a thiol group (-SH) of the polypeptide chain
Improvement of the therapeutic treatment of inflammatory bowel diseases following rectal administration of mesalazine-loaded chitosan microparticles vs Asamax®
No full textThe development of innovative strategies for the efficacious treatment of inflammatory bowel diseases (IBD) still remains a goal for pharmaceutical research. Targeting the lower section of the intestine is the main aim of therapy because it is the compartment primarily affected by IBDs. Mesalazine was microencapsulated in chitosan particles in order to modulate its unfavorable pharmacokinetic profile exploiting the bioadhesive feature of the polysaccharide and increase the anti-inflammatory effect of the drug following its rectal administration in an in vivo model of induced IBD. The chitosan microparticles (1-4 μm mean size) allowed efficient retention of the mesalazine and a prolonged drug release lasting up to 48 h. In vitro and in vivo experiments confirmed the significant mucoadhesion feature of the formulation by means of mucin assay and CLSM experiments and demonstrated its therapeutic efficacy at a drug concentration 2-fold lower than the commercial formulation Asamax® (13 mg/kg vs 26 mg/kg)
- …
