A magnetic endourethral sphincter against stress urinary incontinence: preliminary pilot study in humans.

BACKGROUND: Urinary incontinence (UI) is a common and frustrating condition that affects patients' quality of life as well as the Healthcare systems. Currently, the most severe cases of UI are treated using implanted, invasive artificial sphincters. We propose an innovative, minimally invasive magnetic endourethral sphincter for the treatment of stress UI (SUI) in patients for whom previous medical and surgical treatments have failed. METHODS: Six patients with severe SUI were enrolled at a single center and underwent cystoscopic sphincter implantation. After 10 days, correct device position was confirmed by ultrasonography. The sphincter was explanted after 28 days. RESULTS: In all patients, the sphincter was successfully implanted using an endoscopic approach. One patient reached the end of the pilot test (28 days) with the sphincter correctly placed. Patients' responses on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form questionnaire improved from a score of 18 out of 21 at the screening visit (UI without reasons) to a score of 3 out of 21 (almost perfect continence). No major pain and discomfort were reported. CONCLUSIONS: This study showed the feasibility of sphincter implantation, explantation, and overall tolerability, although a redesign of the sphincter distal part is needed.

Design of an innovative platform for the treatment of cerebral tumors by means of erythro-magneto-HA-virosomes.

Gliomas are the most common intracranial tumors, featured by a high mortality rate. They represent about 28% of all primary central nervous system (CNS) tumors and 80% of all malignant brain tumors. Cytotoxic chemotherapy is one of the conventional treatments used for the treatment, but it often shows rather limited efficacy and severe side effects on healthy organs, due to the low selectivity of the therapy for malignant cells and to a limited access of the drug to the tumor site, caused by the presence of the Blood-Brain Barrier. In order to resolve these limitations, recently an Erythro-Magneto-HA-Virosome (EMHV) drug delivery system (DDS), remotely controllable through an externally applied magnetic field, has been proposed. To accurately localize the EMHV at the target area, a system able to generate an adequate magnetic field is necessary. In this framework, the objective of this paper was to design and develop a magnetic helmet for the localization of the proposed EMHV DDS in the brain area. The results demonstrated, through the implementation of therapeutic efficacy maps, that the magnetic helmet designed in the study is a potential promising magnetic generation system useful for studying the possible usability of the magnetic helmet in the treatment of glioma and possibly other CNS pathologies by EMHV DDS.

Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer.

Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents show a rather limited efficacy. We have recently demonstrated that the atypical cadherin FAT1 is a specific marker of CRC and that the FAT1-specific monoclonal antibody mAb198.3 may offer new therapeutic opportunities for CRC, being efficiently internalized by cancer cells and reducing cancer growth in colon cancer xenograft models. In this study we explored the therapeutic efficacy of mAb198.3 using two drug delivery systems (DDS) for improving the targeted treatment of CRC. The mAb198.3 was either directly bound to super-paramagnetic nanoparticles (spmNPs) or embedded into human erythrocyte-based magnetized carriers, named Erythro-Magneto-Hemagglutinin Virosomes (EMHVs) to produce two different novel mAb198.3 formulations. Both DDS were endowed with magnetic properties and were anchored in the target tumor site by means of an external permanent magnet. The antibody loading efficiency of these two magnetically driven drug delivery systems and the overall therapeutic efficacy of these two formulations were assessed both in vitro and in a proof-of-concept in vivo study. We demonstrated that mAb198.3 bound to spmNPs or embedded into EMHVs was very effective in targeting FAT1-positive colon cancer cells in vitro and accumulating in the tumor mass in vivo. Although both in vivo administered mAb198.3 formulations have approximately 200 lower antibody doses needed, these showed to achieve a relevant therapeutic effect, thus reducing cancer growth more efficiently respect to the naked antibody. These results indicate that the two proposed magnetically driven drug delivery systems have a considerable potential as platforms to improve bioavailability and pharmacodynamics of anti-FAT mAb198.3 and raise new opportunities for a targeted therapy of CRC.

Untethered magnetic millirobot for targeted drug delivery.

This paper reports the design and development of a novel millimeter-sized robotic system for targeted therapy. The proposed medical robot is conceived to perform therapy in relatively small diameter body canals (spine, urinary system, ovary, etc.), and to release several kinds of therapeutics, depending on the pathology to be treated. The robot is a nearly-buoyant bi-component system consisting of a carrier, in which the therapeutic agent is embedded, and a piston. The piston, by exploiting magnetic effects, docks with the carrier and compresses a drug-loaded hydrogel, thus activating the release mechanism. External magnetic fields are exploited to propel the robot towards the target region, while intermagnetic forces are exploited to trigger drug release. After designing and fabricating the robot, the system has been tested in vitro with an anticancer drug (doxorubicin) embedded in the carrier. The efficiency of the drug release mechanism has been demonstrated by both quantifying the amount of drug released and by assessing the efficacy of this therapeutic procedure on human bladder cancer cells.

Experimental assessment of a novel robotically-driven endoscopic capsule compared to traditional colonoscopy.

BACKGROUND: Despite colonoscopy represents the conventional diagnostic tool for colorectal pathology, its undeniable discomfort reduces compliance to screening programmes. AIMS: To evaluate feasibility and accuracy of a novel robotically-driven magnetic capsule for colonoscopy as compared to the traditional technique. METHODS: Eleven experts and eleven trainees performed complete colonoscopy by robotic magnetic capsule and by conventional colonoscope in a phantom ex vivo model (artificially clean swine bowel). Feasibility, overall accuracy to detect installed pins, procedure elapsed time and intuitiveness were measured for both techniques in both operator groups. RESULTS: Complete colonoscopy was feasible in all cases with both techniques. Overall 544/672 pins (80.9%) were detected by experimental capsule procedure, while 591/689 pins (85.8%) were detected within conventional colonoscopy procedure (P=ns), thus establishing non-inferiority. With the experimental capsule procedure, experts detected 74.2% of pins vs. 87.6% detected by trainees (P<0.0001). Overall time to complete colon inspection by robotic capsule was significantly higher than by conventional colonoscopy (556±188s vs. 194±158s, respectively; P=0.0001). CONCLUSION: With the limitations represented by an ex vivo setting (artificially clean swine bowel and the absence of peristalsis), colonoscopy by this novel robotically-driven capsule resulted feasible and showed adequate accuracy compared to conventional colonoscopy.