Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) is recently gaining attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as Single Particle Tracking (SPT) and Fluorescence Correlation Spectroscopy (FCS), we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied in function of the charge (positive or negative) and Poly-Ethylene Glycol (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy.

Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal carcinomatosis (PC). Over the past decade, a lot of effort has been put both in the academia and clinic in developing IP therapeutic approaches that maximize local efficacy while limiting systemic side effects. Also nanomedicines are under investigation for the treatment of tumors confined to the peritoneal cavity, due to their potential to increase the peritoneal retention and to target drugs to the tumor sites as compared to free drugs. Despite the progress reported by multiple clinical studies, there are no FDA approved drugs or formulations for specific use in the IP cavity yet. This review discusses the current clinical management of PC, as well as recent advances in nanomedicines-based IP delivery.We address important challenges to be overcome towards designing optimal nanocarriers for IP therapy in vivo.

Purpose: To assess the value of quantitative T2 signal intensity (SI) and apparent diffusion coefficient (ADC) to differentiate prostate cancer from post-biopsy hemorrhage, using prostatectomy as the reference. Materials and Methods:Forty-five men with prostate cancer underwent prostate magnetic resonance imaging (MRI), including axial T1-weighted imaging (T1WI), T2WI, and single-shot echo-planar image (SS EPI) diffusionweighted imaging. Two observers measured, in consensus, normalized T2 signal intensity (SI) (nT2, relative to muscle T2 SI), ADC, and normalized ADC (nADC, relative to urine ADC) on peripheral zone (PZ) tumors, benign PZ hemorrhage, and non-hemorrhagic benign PZ. Tumor maps from prostatectomy were used as the reference. Mixed model analysis of variance was performed to compare parameters among the three tissue classes, and Pearson's correlation coefficient was utilized to assess correlation between parameters and tumor size and Gleason score. Receiver-operating characteristic (ROC)-curve analysis was used to determine the performance of nT2, ADC, and nADC for diagnosis of prostate cancer.Results: nT2, ADC, and nADC were significantly lower in tumor compared with hemorrhagic and non-hemorrhagic benign PZ (P < 0.0001). There was a weak but significant correlation between ADC and Gleason score (r ¼ À0.30, P ¼ 0.0119), and between ADC and tumor size (r ¼ À0.40, P ¼ 0.0027), whereas there was no correlation between nT2 and Gleason score and tumor size. The areas under the curve to distinguish tumor from benign hemorrhagic and non-hemorrhagic PZ were 0.97, 0.96, and 0.933 for nT2, ADC, and nADC, respectively. Conclusion:Quantitative T2 SI and ADC/nADC values may be used to reliably distinguish prostate cancer from post-biopsy hemorrhage.

Abstract:Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the Introduction:

The rising antimicrobial resistance contributes to 25000 annual deaths in Europe. This threat to the public health can only be tackled if novel antimicrobials are developed, combined with a more precise use of the currently available antibiotics through the implementation of fast, specific, diagnostic methods. Nucleic acid mimics (NAMs) that are able to hybridize intracellular bacterial RNA have the potential to become such a new class of antimicrobials and additionally could serve as specific detection probes. However, an essential requirement is that these NAMs should be delivered into the bacterial cytoplasm, which is a particular challenge given the fact that they are charged macromolecules. We consider these delivery challenges in relation to the gastric pathogen Helicobacter pylori, the most frequent chronic infection worldwide. In particular, we evaluate if cationic fusogenic liposomes are suitable carriers to deliver NAMs across the gastric mucus barrier and the bacterial envelope. Our study shows that DOTAP-DOPE liposomes post-PEGylated with DSPE-PEG (DSPE Lpx) can indeed successfully deliver NAMs into Helicobacter pylori, while offering protection to the NAMs from binding and inactivation in gastric mucus isolated from pigs. DSPE Lpx thus offer exciting new possibilities for in vivo diagnosis and treatment of Helicobacter pylori infections.

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Many polycation-based gene delivery vectors show high transfection in vitro, but their cationic nature generally leads to significant toxicity and poor in vivo performance which significantly hampers their clinical applicability. Unlike conventional polycation-based systems, decationized polyplexes are based on hydrophilic and neutral polymers. They are obtained by a 3-step process: charge-driven condensation followed by disulfide crosslinking stabilization and finally polyplex decationization. They consist of a disulfide-crosslinked poly(hydroxypropyl methacrylamide) (pHPMA) core stably entrapping plasmid DNA (pDNA), surrounded by a shell of poly(ethylene glycol) (PEG). In the present paper the applicability of decationized polyplexes for systemic administration was evaluated. Cy5-labeled decationized polyplexes were evaluated for stability in plasma by fluorescence single particle tracking (fSPT), which technique showed stable size distribution for 48 h unlike its cationic counterpart. Upon the incubation of the polymers used for the formation of polyplexes with HUVEC cells, MTT assay showed excellent cytocompatibility of the neutral polymers. The safety was further demonstrated by a remarkable low teratogenicity and mortality activity of the polymers in a zebrafish assay, in great contrast with their cationic counterpart. Near infrared (NIR) dye-labeled polyplexes were evaluated for biodistribution and tumor accumulation by noninvasive optical imaging when administered systemically in tumor bearing mice. Decationized polyplexes exhibited an increased circulation time and higher tumor

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