Biomedical subjects

M R Gasco

Publications and source records attributed to M R Gasco.

At least 19 recordsLinked to original sources

PubMed2004

Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line.

Solid lipid nanoparticles (SLN) carrying cholesteryl butyrate (chol-but), doxorubicin and paclitaxel had previously been developed, and the antiproliferative effect of SLN formulations versus conventional drug formulations was here evaluated on HT-29 cells. The 50% inhibitory concentration (IC(50) values were interpolated from growth curves obtained by trypan blue exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC(50 72 h) 0.3 +/- 0.03 mM vs >0.6 mM) and doxorubicin (IC(50 72 h) 81.87 +/- 4.11 vs 126.57 +/- 0.72 nM) was higher than that of conventional drug formulations. Intracellular doxorubicin was double after 24 h exposure to loaded SLN versus the conventional drug formulation, at the highest concentration evaluated by flow cytometry. In vitro cytotoxicities of paclitaxel-loaded SLN and conventional drug formulation (IC(50 72 h) 37.36 +/- 6.41 vs 33.43 +/-1.17 nM) were similar. Moreover, the combination of low concentrations of chol-but SLN (0.1-0.2 mM) and doxorubicin (1.72 nM) or paclitaxel (1.17 nM) exerted a greater-than-additive antiproliferative effect at 24 h exposure, while the combination of Na-but and doxorubicin or paclitaxel did not. These preliminary in vitro results suggest that SLN could be proposed as alternative drug delivery system.

Antineoplastic Agents↗

PubMed2003

Nocturnal anomalous movement reduction and sleep microstructure analysis in parkinsonian patients during 1-night transdermal apomorphine treatment.

This study analyzed the macrostructure and microstructure of sleep in 12 parkinsonian patients under basal conditions (T0) and during 1-night treatment (T1) with a new formulation of apomorphine. This new formulation consisted in a microemulsion of apomorphine administered by the transdermal route, able to provide a constant release of the drug over several hours (APO-TD). Sleep analysis at T1 compared with T0 revealed a 16% increment of total sleep time, a 12% increment of sleep efficiency, a 16% increment of stage 3 and 4 non-REM sleep, a 15% reduction of periodic limb movements index, a 22% reduction of arousal index, and a 23% reduction of cycling alternating patterns/non-REM. We conclude that APO-TD may be able to reduce nocturnal anomalous movements, akinesia, and rigidity in Parkinson's disease, and may reduce the disturbed sleep typical of Parkinson's disease.

Administration, Cutaneous↗

PubMed2002

Controlled-release transdermal apomorphine treatment for motor fluctuations in Parkinson's disease.

This study evaluated the efficacy in Parkinson's disease (PD) of a new pharmacologic preparation of apomorphine included in microemulsions and administered by transdermal route, which provides a constant release of the drug for several hours (Apo-TD). Twenty-one PD patients with motor fluctuations were treated with L-dopa alone, with L-dopa plus oral dopamine-agonists, or with L-dopa plus Apo-TD. Apo-TD improved UPDRS-III and tapping test scores in "off" conditions, and reduced duration of "off" periods; no improvement in "on" conditions occurred. We conclude that Apo-TD shows its efficacy particularly by reducing "off" period duration and disability rather than improving motor performances in "on" conditions and therefore it seems a promising treatment for uncontrolled "off" phases in PD patients.

Administration, Cutaneous↗

PubMed2001

Transdermal permeation of apomorphine through hairless mouse skin from microemulsions.

The in vitro transdermal absorption of apomorphine from microemulsions was studied using the skin of the hairless mouse as a membrane. Two microemulsions (no. 1 and 2) were prepared and thickened both containing 3.9% of apomorphine hydrochloride. The lipophilicity of the drug was increased by forming apomorphine-octanoic acid ion-pairs. The fluxes of the drug from the microemulsions through hairless mouse skin were 100 microg h(-1) cm(-2) from no. 1 and 88 microg h(-1) cm(-2) from no. 2. Apomorphine in microemulsions, protected from light with antioxidants, showed no degradation for up to 6 months.

Administration, Cutaneous↗

PubMed2001

Transmucosal transport of tobramycin incorporated in solid lipid nanoparticles (SLN) after duodenal administration to rats. Part II--tissue distribution.

Tobramycin-loaded solid lipid nanoparticles (SLN) were prepared and administered by duodenal and intravenous (i.v.) routes to rats and the tissue distributions were determined successively at fixed times (30 min, 4 h and 24 h) and compared to those of the tobramycin solution after i.v. administration. The tissue distribution between tobramycin-loaded SLN administered duodenally and i.v. was different. A marked difference between tobramycin-loaded SLN administered duodenally and tobramycin solution administered i.v. was also evidenced. In particular, the amounts of tobramycin in the kidneys after tobramycin-loaded SLN administration either duodenally or i.v. were lower than after administration of i.v. solution. Tobramycin-loaded SLN were able to pass across the blood-brain barrier in rats to a greater extent after i.v. injection than after duodenal administration.

Animals↗

PubMed2001

The effect of formulation and concentration of cholesteryl butyrate solid lipid nanospheres (SLN) on NIH-H460 cell proliferation.

Experimental factorial design was used to evaluate the influence of two factors involved in producing cholesteryl butyrate (chol-but) solid lipid nanospheres (SLN), microemulsion formulation and microemulsion/water ratio, on the effect of the SLN on the proliferation of NIH-H460, a non-small-cell lung carcinoma; six experimental settings were tested. The cells were treated with scalar concentrations of cholesteryl butyrate (from 0.008 to 1.000 mM) for each experimental condition; NIH-H460 cell growth was inhibited in all cases. The best experimental setting provided complete inhibition at 0.125 mM chol-but, while at the same concentration sodium butyrate provided only 38% inhibition.

Butyric Acid↗

PubMed2001

Evaporative drying of aqueous dispersions of solid lipid nanoparticles.

Solid lipid nanoparticles (SLNs) have been proposed as alternative colloidal drug carriers. SLNs are obtained by dispersing warm oil-in-water microemulsions into cold water. The aim of this research was to investigate an evaporative drying process for aqueous dispersions of SLNs. For this purpose, a special apparatus, namely a thermostatic minidesiccator having alumina as the drying medium, was designed to carry out the evaporative drying at a controlled temperature. Besides the water removal kinetics, the mean particle size and the size distribution of SLNs were measured during the during with the aim of detecting the highest temperature at which the drying process can be carried out without significantly affecting the SLN average diameter. The SLN dispersions were evaluated with and without a hydrophilic excipient, commonly used as a cryoprotector (trehalose). The drying temperature of 10 degrees C was found to be the most suitable for obtaining SLNs as a powder, maintaining almost the same size as that of the SLNs in dispersion.

Desiccation↗

PubMed2000

Cellular uptake and cytotoxicity of solid lipid nanospheres (SLN) incorporating doxorubicin or paclitaxel.

Solid Lipid Nanospheres (SLN) are colloidal therapeutic systems proposed for several administration routes and obtained by dispersing warm microemulsions in cold water. SLN as carriers of doxorubicin and paclitaxel have been previously studied. In this study, the cellular uptake of SLN and the cytotoxicity of doxorubicin and paclitaxel incorporated into SLN were investigated on two cell-lines, human promyelocytic leukemia (HL60) and human breast carcinoma (MCF-7). Cellular uptake of SLN was determined by incorporating 6-coumarin as fluorescent marker. The cellular uptake of fluorescent SLN was clearly evidenced by fluorescence microscopy. The cytotoxicity of doxorubicin incorporated in SLN was higher compared to the conventional doxorubicin solution, even at the lower concentrations. Paclitaxel in SLN was about 100-fold more effective than free paclitaxel on MCF-7 cells, while on HL60 cells a lower sensitivity was achieved with paclitaxel in SLN. Unloaded SLN had no cytotoxic effect on HL60 and MCF-7 cells.

Antibiotics, Antineoplastic↗

PubMed2000

Scale-up of the preparation process of solid lipid nanospheres. Part I.

An apparatus was designed to prepare solid lipid nanospheres (SLN), potential colloidal therapeutic system obtained by dispersing a warm oil-in-water (o/w) microemulsion in cold water. The apparatus, consisting mainly of a thermostated aluminium chamber and a pneumatic piston, permitted to disperse through a needle up to 100 ml of warm microemulsion and to vary the temperature, the dispersing rate and the drop size of the warm o/w microemulsion. Experimental design was applied to study the effect of four experimental factors, such as chamber temperature, piston pressure, needle gauge and volume of dispersing water, on average diameter and polydispersity index of SLN and on dispersing time of microemulsion (the time required for the microemulsion to drip completely from the apparatus). The results showed that temperature and pressure play the most important roles depending on the needle gauge used. In particular, the smallest SLN were obtained using high temperature and pressure values and a small needle gauge.

Colloids↗

PubMed2000

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats.

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin were prepared as drug delivery systems. The pharmacokinetics and tissue distribution of doxorubicin in these SLN were studied after i.v. administration to conscious rats and were compared to the commercial solution of doxorubicin. The same dose of each formulation (6 mg kg(-1)of body weight) of doxorubicin was injected in the rat jugular vein. Blood samples were collected after 1, 15, 30, 45, 60 min and 2, 3, 6, 12, and 24 h after the injection. Rats were sacrificed after intervals of 30 min, 4 h, and 24 h and samples of liver, spleen, heart, lung, kidney, and brain were collected. In all samples, the concentration of doxorubicin and of the metabolite, doxorubicinol, were determined. Doxorubicin and doxorubicinol were still present in the blood 24 h after injection of stealth and non-stealth SLN, while they were not detectable after the injection of the commercial solution. The results confirmed the prolonged circulation time of the SLN compared to the doxorubicin solution. In all rat tissues, except the brain, the amount of doxorubicin was always lower after the injection of the two types of SLN than after the injection of the commercial solution. In particular, SLN significantly decreased the heart concentration of doxorubicin.

Animals↗

PubMed2000

Transmucosal transport of tobramycin incorporated in SLN after duodenal administration to rats. Part I--a pharmacokinetic study.

Tobramycin-loaded solid lipid nanospheres (SLN) were prepared and administered to rats into the duodenum; their behaviour was compared to that of tobramycin-loaded SLN administered intravenously (i.v.). A tobramycin control solution was also administered to rats. Tobramycin in solution is not absorbed by the gastrointestinal route, while tobramycin incorporated in the SLN is absorbed. A high concentration of tobramycin is still present in plasma 24 hours after the duodenal administration of tobramycin-loaded SLN. Tobramycin-loaded SLN administered i.v. showed a prolonged circulation time compared to the i.v. administered tobramycin solution. The AUC of tobramycin in SLN administered duodenally is higher than those of tobramycin in SLN and in solution administered i.v.

Animals↗

PubMed2000

Preparation and characterization of solid lipid nanospheres containing paclitaxel.

The study describes the development of stealth and non-stealth solid lipid nanospheres (SLNs) as colloidal carriers for paclitaxel, a drug with very low solubility. SLNs are constituted mainly of bioacceptable and biodegradable lipids, such as tripalmitin and phosphatidylcholine, and can incorporate amounts of paclitaxel up to 2.8%. Stealth and non-stealth loaded SLNs are in the nanometer size range and can be sterilized and freeze-dried. Thermal analysis (differential scanning calorimetry) showed that paclitaxel is not able to crystallize in the SLNs. Release of paclitaxel from SLNs is very low. Non-stealth and stealth SLNs are stable over time without precipitation of paclitaxel and can be proposed for its parenteral administration.

Antineoplastic Agents, Phytogenic↗

PubMed2000

In vitro effects of cholesteryl butyrate solid lipid nanospheres as a butyric acid pro-drug on melanoma cells: evaluation of antiproliferative activity and apoptosis induction.

Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G(0/1)-S transition block and a 'sub-G(0/1)' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.

Annexin A5↗

PubMed2000

Biodistribution of stealth and non-stealth solid lipid nanospheres after intravenous administration to rats.

Drug-free stealth and non-stealth solid lipid nanospheres (SLNs) were administered intravenously to rats to evaluate their tissue distribution and their transport across the blood-brain barrier. Two types of experiments were performed using unlabelled and labelled SLNs. Rats were administered labelled non-stealth or stealth nanospheres (NSSLNs and SSLNs) and their tissue distribution was monitored for 60 min. In another experiment, rats were injected with unlabelled NSSLNs or SSLNs and the cerebrospinal fluid (CSF) was analysed using transmission electron microscopy (TEM) to confirm the presence of the SLNs. Some differences were found in the biodistribution between labelled NSSLNs and SSLNs. In particular, the radioactivity in the liver and the lung was much lower for SSLNs than for NSSLNs, confirming a difference in their uptake. Both types of SLNs were detected in the brain. TEM analysis showed both types of SLNs in rat CSF.

Animals↗

PubMed1999

Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with beta-cyclodextrins.

Inclusion complexes of hydrocortisone and progesterone were formed with beta-cyclodextrin or 2-hydroxypropyl-beta-cyclodextrin. The formation of the complexes was confirmed by differential scanning calorimetry (DSC). The inclusion complexes were incorporated in two types of solid lipid nanoparticles (SLN). In the presence of the complexes the sizes of SLN remained below 100 nm. DSC analysis showed that hydrocortisone and progesterone are dispersed in SLN in an amorphous state. Using the beta-cyclodextrin complexes the incorporation of the more hydrophilic drug, hydrocortisone, was higher than that of progesterone. Release of hydrocortisone and progesterone from SLN was lower when they were incorporated as inclusion complexes than as free molecules.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1999

Pharmacokinetics of doxorubicin incorporated in solid lipid nanospheres (SLN).

The pharmacokinetics of doxorubicin incorporated as ion-pair into solid lipid nanospheres (SLN) was compared with that of the commercial solution of the drug. Male albino rats (Wistar-derived strain) were treated i.v. with equivalent doses (6 mg kg(-1)) of two different doxorubicin formulations: an aqueous dispersion of SLN carrying doxorubicin and a commercial doxorubicin solution (Adriablastina). These formulations were injected, under general anaesthesia, through a cannula into the jugular vein and blood samples were collected at 1, 15, 30, 45, 60, 120 and 180 min after administration. After 180 min rats were killed and samples of liver, heart, lung, kidney, spleen and brain were collected. Blood and tissue samples were analysed by a spectrofluorimetric method. The anthracycline concentration in the blood was markedly higher at each point times with the SLN than with the commercial solution. The drug concentration was also higher in the lung, spleen and brain. SLN-treated rats showed a lower doxorubicin concentration in liver, heart and kidney. The results showed that SLN increased the area under the curve (0-180 min) of doxorubicin compared to conventional doxorubicin solution and led to a different body distribution profile.

Animals↗

PubMed1998

NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes.

This work deals with the preparation and relaxometric investigations of solid lipid nanoparticles (SLN) containing [Gd-DTPA(H2O)]2- and [Gd-DOTA(H2O)]-. These paramagnetic chelates are commonly used as contrast agents (CA) for magnetic resonance imaging (MRI) owing to their ability to strongly increase the tissue water proton relaxation rate. The amount of gadolinium(III) (Gd(III)) complex included in the SLN has been evaluated and, on this basis, it has been found that the longitudinal relaxivity of these Gd(III) chelates apparently does not vary, at physiological pH, following their inclusion in SLN. We are unable to establish whether this is due to the free exchange of water from the inner compartment containing the Gd(III) chelate to the bulk water or whether the observed relaxation rate is essentially determined by a fraction of the complex which is close to the surface of the SLN in a region easily accessible to the bulk water. At acidic pH values, the relaxivity of the paramagnetic SLN containing the less thermodynamically and kinetically stable [Gd-DTPA(H2O)]2- markedly increases. This effect may be ascribed to an increased immobilization and/or to an enhanced hydration of the complex on SLN.

Contrast Media↗

PubMed1998

Solid lipid nanoparticles in lymph and plasma after duodenal administration to rats.

PURPOSE: To evaluate the uptake and transport of solid lipid nanoparticles (SLN), which have been proposed as alternative drug carriers, into the lymph and blood after duodenal administration in rats. METHODS: Single doses of two different concentrations of aqueous dispersions of unlabelled and labelled SLN (average diameter 80 nm) were administered intraduodenally to rats. At different times, samples of lymph were withdrawn by cannulating the thoracic duct and blood was sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for unlabelled and labelled SLN respectively. The biological samples were analysed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and gamma-counting. RESULTS: TEM analysis evidenced SLN in lymph and blood after duodenal administration to rats: the size of SLN in lymph did not change markedly compared to that before administration. The labelled SLN confirmed the presence of SLN in lymph and blood. CONCLUSIONS: The uptake and transport of SLN in the lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical stability of SLN may have important implications in designing drug-carrying SLN.

Animals↗