Alberto Valazza

Solid Lipid Nanoparticles for Potential Doxorubicin Delivery in Glioblastoma Treatment: Preliminary In Vitro Studies

The major obstacle to glioblastoma pharmacological therapy is the overcoming of the blood-brain barrier (BBB). In literature, several strategies have been proposed to overcome the BBB: in this experimental work, solid lipid nanoparticles (SLN), prepared according to fatty acid coacervation technique, are proposed as the vehicle for doxorubicin (Dox), to enhance its permeation through an artificial model of BBB. The in vitro cytotoxicity of Dox-loaded SLN has been measured on three different commercial and patient-derived glioma cell lines. Dox was entrapped within SLN thanks to hydrophobic ion pairing with negatively charged surfactants, used as counterions. Results indicate that Dox entrapped in SLN maintains its cytotoxic activity toward glioma cell lines; moreover, its permeation through hCMEC/D3 cell monolayer, assumed as a model of the BBB, was increased when the drug was entrapped in SLN. In conclusion, SLN proved to be a promising vehicle for the delivery of Dox to the brain in glioblastoma treatment.

In vitro description of a new technique for stapled side-to-side jejunocecal anastomosis in horses and CT scan anatomical comparison with other techniques

BackgroundStapled jejunocecal anastomoses are commonly performed in equine abdominal surgery. They carry higher complication rates compared to handsewn techniques. In human surgery various causes likely to lead to failure of stapled techniques have been evaluated, including staple line failure. Recently Freeman proposed a technique to perform a stapled jejunocecal anastomosis in horses while avoiding blind pouch formation. The aim of this study is to describe a method for stapled side-to-side jejunocecal anastomosis in horses and to compare it with other techniques with computed tomography to assess stomal area, shape and blind pouch size.MethodsIntestinal specimens comprising the cecum, ileum and jejunum from 18 horses were collected and were divided into three groups. In Group S a standard stapled side-to-side jejunocecal anastomosis was performed. In Group F the anastomosis was performed using a modified technique proposed by Freeman. In Group G the anastomosis was performed with a modified technique proposed by the authors. Inflated bowel segments were CT scanned to obtain a MultiPlanar Reconstruction of the stoma and afferent small intestine before calculating the cross-sectional area of each of these regions. The ratio of the measured areas was compared between the three techniques. The volume of the blind-end pouch was measured and its ratio with the intestinal area compared between techniques. The cecum was opened and the length of the stoma measured with a caliper and compared to the intended initial length.ResultsThe stomal/intestinal area ratio was not significantly different between techniques.No statistically significant difference was found in the stomal ideal/real perimeter ratio.There was no statistically significant difference in the intended/real stomal length ratio, and all techniques featured an increase in stomal length ranging from 2 to 12 %. Blind pouch formation was a consistent finding in Group S and was virtually absent in Groups F and G.ConclusionsBoth the Freeman and the new (G) technique were comparable to the standard technique in terms of stomal area, stomal shape and difference in stomal elongation. They consistently produced a smaller blind pouch and allowed easier placement of the staplers.

Solid lipid nanoparticles by coacervation loaded with a methotrexate prodrug: preliminary study for glioma treatment

AIM Methotrexate-loaded biocompatible nanoparticles were tested for preliminary efficacy in glioma treatment. MATERIALS & METHODS Behenic acid nanoparticles, prepared by the coacervation method, were loaded with the ester prodrug didodecylmethotrexate, which was previously tested in vitro against glioblastoma human primary cultures. Nanoparticle conjugation with an ApoE mimicking chimera peptide was performed to obtain active targeting to the brain. RESULTS & CONCLUSION Biodistribution studies in healthy rats assessed the superiority of ApoE-conjugated formulation, which was tested on an F98/Fischer glioma model. Differences were observed in tumor growth rate (measured by MRI) between control and treated rats. In vitro tests on F98 cultured cells assessed their susceptibility to treatment, with consequent apoptosis, and allowed us to explain the apoptosis observed in glioma models.

Ex Vivo Anatomical Characterization of Handsewn or Stapled Jejunocecal Anastomosis in Horses by Computed Tomography Scan

The aim of this study is to compare handsewn and stapled jejunocecal anastomosis with different stomal lengths in terms of anatomical differences. Group 1 underwent a two-layer handsewn jejunocecal side-to-side anastomosis (HS); Group 2 received a stapled jejunocecal side-to-side anastomosis (GIA). Each group was divided into two subgroups (HS80 and HS100, GIA80 and GIA100). Specimens were inflated and CT scanned. The stomal/jejunal area ratio and blind end pouch volume/area were measured and compared. Effective length of the stoma was measured and compared with the initial length. Stomal/jejunal area ratio was 1.1 for both 80 techniques, 1.6 for the GIA100, and 1.9 for the HS100 technique. Both HS and GIA techniques produced a blind end pouch and exhibited a mean increase of the final stomal length ranging from 6 to 11% greater than the original stomal length. All techniques will exhibit a length increase of the final stomal length compared to the intended stomal length, with a consequent increase in stomal area. Stapled techniques consistently produced a large distal blind end pouch. Length of a jejunocecal anastomosis should be selected in accordance with the diameter of afferent jejunum, and the 80 mm stomal length could be deemed sufficient in horses.