1,721,005 research outputs found
FOCUS ON NANOSTRUCTURED LIPID CARRIERS AND MONOOLEIN AQUEOUS DISPERSIONS
No full textNowadays, everyone feels the impact of nanotechnology in his life. There is a trend that urges
people to revisit many research areas with a nano-view, in order to understand how the same
thing can work at nano- level. This phenomenon is revolutionizing pharmaceutical sciences and
many drugs are being reformulated for possibilities of delivering as a nanosystem.
In recent years, a particular attention has been focused on new generations of lipid
nanoparticles such as nanostructured lipid carriers (NLC), a second generation of solid lipid
nanoparticles (SLN), and monoolein aqueous dispersions (MAD), derived from the mesophases
originated from the system monoolein/water/poloxamer.
In this thesis different NLC, SLN or MAD formulations were developed as drug delivery systems
specifically for antiparkinson or antimycotic drugs, in order to prolong their action and reduce
the side effects. Bromocriptine (BC), new synthetized L-DOPA derivatives (Der-A, Der-B, Der-C
and Der-D) or Clotrimazole (CLO) have been alternatively chosen as model drugs. Physical and
chemical characterizations have been performed on the obtained formulations. In vitro and in
vivo studies permitted to obtain release kinetics and evaluate the effectiveness of
nanoparticulate systems.
BC containing NLC and MAD showed high entrapment efficiency and X-ray diffraction analyses
demonstrated that the presence of BC did not affect the scattering profile. In this case, different
in vitro experimental approaches were evaluated, showing that the in vitro release of poorly
water soluble drugs (as BC) is more affected by the composition of the receiving phase (i.e. in
term of presence of water miscible polar organic solvents) rather than by the experi modality adopted for the in vitro determinations. In vivo studies demonstrated that only BC-NLC
were able to markedly attenuate motor deficit in 6-OHDA hemilesioned rats, suggesting that
NLC represent a more effective carrier to prolong the half-life of BC in vivo.
All L-DOPA derivatives were successfully incorporated in NLC. The produced formulations
resulted homogeneous in terms of size and remain stable until two months from the preparation.
Morphological characterization highlighted that no substantial difference characterized empty
and derivatives containing NLC. In vitro kinetics release highlighted that NLC were able to
release the contained derivatives in a controlled manner and permit to select Der-A for in vivo
tests. In vivo tests demonstrated that the Der-A possess antiparkinson activity.
The inclusion of Der-A in SLN, performed using three different concentrations of prodrug,
showed different entrapment efficiencies depending on the quantity of active employed.
Calorimetric test evidenced an effective interaction between lipid phase and the prodrug. In vitro
studies demonstrated a controlled release of Der-A from SLN, also thanks to the extension of
the half-life of the prodrug.
CLO was incorporated both in MAD and in NLC with high recovery. Shelf life stability evidenced
that the solid matrix of NLC enabled to control drug degradation better than MAD. In vitro
experiments on candida cells demonstrated that CLO-MAD and CLO-NLC exhibit a higher
activity than the free drug.
The gelification of CLO containing nanoparticles permitted to obtain formulations able to remain
on the mucosa surface. Micro calorimetric assays confirmed that poloxamer formulated gels are
able to change their structure, with a rapid passage from liquid to solid (crystalline) form at a
temperature lower than vaginal temperature, allowing a selective action in the site of application.
Finally it is noteworthy that the production of CLO-NLC poloxamer gel is simple and suitable for
industry scaling up
Size characterization by Sedimentation field flow fractionation of silica particles used as food additives
No full textFour types of SiO2, available on the market as additives in food and personal care products, were size characterized using Sedimentation Field Flow Fractionation (SdFFF), SEM, TEM and Photon Correlation Spectroscopy (PCS). The synergic use of the different analytical techniques made it possible, for some samples, to confirm the presence of primary nanoparticles (10 nm) organised in clusters or aggregates of different dimension and, for others, to discover that the available information is incomplete, particularly that regarding the presence of small particles. A protocol to extract the silica particles from a simple food matrix was set-up, enriching (0.25% w/w) a nearly silica-free instant barley coffee powder with a known SiO2 sample. The SdFFF technique, in conjunction with SEM observations, made it possible to identify the added SiO2 particles and verify the new particle size distribution. The SiO2 content of different powdered foodstuffs was determined by graphite furnace atomic absorption spectroscopy (GF-AAS); the concentrations ranged between 0.006 - 0.35% w/w. The protocol to isolate the silica particles was so applied to the most SiO2-rich commercial products and the derived suspensions were separated by SdFFF; SEM and TEM observations supported the size analyses while GFAAS determinations on collected fractions permitted element identification
Niosomi contenenti molecole biotecnologiche ad attivita’ antierpetica somministrati per via nasale
No full textEudragit® microparticles for the release of budesonide: A comparative study
No full textThis study compares the behaviour of budesonide-containing microparticles made of Eudragit® RS or Eudragit® RS/Eudragit® RL 70:30 (w/w) prepared either by solvent evaporation or spray-drying technique. The loading efficiency of budesonide within microparticles was about 72% for microparticles prepared by solvent evaporation and around 78% for spray-dried microparticles. Thermal analyses were assessed to collect information about the structural stability of budesonide within the polymeric microspheres. The in vitro release was performed using simulating gastric (fasted state simulated gastric fluid) and intestinal (fasted state simulated intestinal fluid) fluids as the receiving solutions. After 3 h the drug release from Eudragit® RS/Eudragit® RL microparticles was about 6-fold higher than that obtained in the case of monopolymer microparticles. Using fasted state simulated intestinal fluid the drug was released between 4 and 30% in both types of preparations. Eudragit® RS microparticles showed a better protection of the drug from gastric acidity than those of Eudragit® RS/Eudragit® RL allowing us to propose Eudragit® RS microparticles as a hypothetical system of colon specific controlled delivery
Preparation and characterization of microparticles containing budesonide
No full textTo study different formulations of Budesonide-containing microparticles for a colon-specific delivery of the drug to treat Crohn’s disease. Microparticles were prepared by solvent evaporation technique. The organic phase (10%) was composed by 5% (w/v) of polymer in methilene chloride and Budesonide 0.05% (w/v), while the dispersing phase was a solution of PVA 0.1% (w/w). Size and morphology of the obtained microparticles were analyzed by optical and scanning electron microscopies. The loading efficiency of Budesonide within microparticles was determined by HPLC and DSC analyses. The “in vitro” release was performed using receiving solutions able to simulate gastric (FaSSGF) and intestinal (FaSSIF) conditions. The amount of Budesonide released was quantified by HPLC. Microparticles of Eudragit RS100 or of Eudragit RS100/Eudragit RL100 70:30 (w/w) were prepared. The production yields were about 92% both in Eudragit RS100 microparticles and Eudragit RS100/RL100 particles. The mean diameters of microparticles preparations were superimposable being 24.86 μm ± 5.97 in the first case and 22.86 μm ± 6.24 in the second one. The DSC analysis confirms an interaction between the drug and the polymers. The loading efficiency of Budesonide was about 12% in the two preparations with only few variations. The “in vitro” studies, performed both in FaSSGF and in FaSSIF solutions, showed that after 3 hours the drug release from Eudragit RS100/RL100 microparticles was about six-fold higher than that obtained with monopolymer formulation (3.56% vs 22.92%). The intestinal simulating release after 6 hours was similar in both preparations (24.45% vs 23.87%). Microparticles produced with Eudragit RS100 showed a better protection of the drug from gastric acidity than Eudragit RS100/RL100 microparticles and an hypothetical system of colon specific controlled deliver
Development of polymethacrylic/poloxamer microparticles for topical administration of biotech drugs
No full textThe aim of this study was to produce biocompatibile microparticles for the mucosal administration of aminoacid based molecules. As aminoacid based molecules, two biotech drugs, namely BPTI (bovine pancreatic trypsin inhibitor) and DTK, a 15 aminoacids sequence derived from HSV-1 glycoprotein B, were employed. Microparticles were prepared using a blend of polymethacrylic polymer and poloxamer 407 in a weight ratio of 50:30:20. A water-in-oil-in-water double emulsion method was employed. As dispersing phase a PVA solution (2.5% w/w) was used.
Microparticles size, polydispersity and morphology were investigated by optical and scanning electron microscopy observations. The loading efficiency of drugs within microparticles was determined by double monochromator spectrophotometer for BPTI and by HPLC for DTK. In vitro drug release profile was obtained by dialysis method using acetate buffer as receiving buffer. The amount of BPTI and DTK released was quantified by HPLC analyses using respectively a gel filtration or an inverse phase column. After the incorporation of both biotech drugs, the obtained microparticles maintained a round shape and a narrow size distribution. Particularly, microparticles showed a mean size of 8.56 μm ± 7.9 and of 7.24 μm ± 6.2 for BPTI and DTK, respectively. Nevertheless, the entrapment efficiency was 67.5% in the case of BPTI and 79.7% in the case DTK.
The in vitro studies showed that the release of biotech drugs from microparticles was slower with respect to that of the corresponding control solutions. In particular, the release of DTK began after the fifth hour and after the first hour for BPTI, reaching after 24 h a release of 20.6% for DTK and of 42.1% for BPTI. The present study suggests that these polymethacrylic/poloxamer microparticles, characterized by a slow and prolonged release, could be a feasible strategy to topically deliver proteins and peptides
Macromolecular carriers to enhance distamycins’ activity
No full textDistamycins are compounds displaying antiviral, antibiotic and interesting antiprotozoal activity related to their ability to reversibly bind to the minor groove of DNA. In this study, we compared the performances of (a) liposomes and micellar systems to deliver A semi-synthetic distamycins and (b) liposomes and ethosomes as specialized delivery systems for benzo-heterocyclic distamycins. In the first case, the analysis of the in vitro antiproliferative activity on cultured human K562 and mouse L1210 leukemic cells demonstrated that liposomes and micellar solutions containing distamycins exert quite different effects as compared to that shown by the free drug depending on the type of drug and also of the cell line used. The activity of distamycins released by specialized delivery systems is in many cases higher with respect to the correspondent drug tested in the free form. In the second case, the analysis of the in vitro antiproliferative activity of distamycin A and its benzoheterocyclic derivatives on cultured human K562 and mouse leukemic L1210 cells demonstrated that the drugs administrated within vesicles are more effective than the corresponding free form used in the same conditions. The obtained results suggest that the enhancement of drug activity expressed by distamycins administrated by macromolecular carrier could reduce or minimize the toxicity occurring with high dosage of distamycins
Intranasal immunization with non-ionic surfactant vescicles containing a secreted recombinant form of gB protein confers protective immunity against genital herpes in mice
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