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Scope: Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L-cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP-1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP-1 release which results in a decrease food intake. Methods and Results: α-Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP-1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP-1 secretion. Single-dose orally given αLA loaded mesoporous particles increased plasma active GLP-1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice. Conclusions: αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.

Mesoporous silicon and silica-based particles have recently been synthesized and proposed for the controlled delivery of several drugs [1,2]. On the other hand, nature and in particular marine organisms have been the source and inspiration for the development of different biomedical applications, including drug delivery devices [3]. On the border of both rests diatoms exoskeletons, nature-made porous silica-based microparticles with amazing morphological features, promising a high potential in drug delivery. Nevertheless, its safety and drug permeability on oral formulations have not yet been studied. In this study, we have demonstrated that diatoms silica microparticles (DSM) have almost no toxicity in colon cancer cells Caco-2, HT- 29, HCT-116 and Caco-2/HT-29, even at concentrations as high as 1000 μg/mL. Moreover, the delivery profile of two common drugs to address gastrointestinal diseases, mesalamine (antiinflammatory) and prednisone (glucocorticosteroid). DSMs are able to release prednisone in a controlled manner and change its absorption pattern, which may improve the safety of its administration. In addition, DSMs can enhance the permeation of mesalamine. These results confirm the potential of DSMs for the development of oral formulations for the therapy of gastrointestinal diseases.

In this study, the antibacterial efficacy of NO-releasing porous silicon nanoparticles (pSiNPs) is reported. NO-releasing pSiNPs were produced via the conjugation of S-nitrosothiol (SNO) and S-nitrosoglutathione (GSNO) donors to the nanoparticle surfaces. The release of the conjugated NO caused by the decomposition of the conjugated SNO and GSNO was boosted in the presence of ascorbic acid. The released NO was bactericidal to Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), and eliminated bacterial growth within 2 h of incubation without compromising the viability of mammalian cells. These results demonstrate the advantages of NO-releasing pSiNPs for antibacterial applications, for example, in chronic wound treatment. Refereed/Peer-reviewed

In this study, thermally hydrocarbonised porous silicon nanoparticles (THCpSiNPs) capped with polyethylenimine (PEI) were fabricated, and their potential for small interfering RNA (siRNA) delivery was investigated in an in vitro glioblastoma model. PEI coating following siRNA loading enhanced the sustained release of siRNA, and suppressed burst release effects. The positively-charged surface improved the internalisation of the nanoparticles across the cell membrane. THCpSiNP-mediated siRNA delivery reduced mRNA expression of the MRP1 gene, linked to the resistence of glioblastoma to chemotherapy, by 63% and reduced MRP1-protein levels by 70%. MRP1 siRNA loaded nanoparticles did not induce cytotoxicity in glioblastoma cells, but markedly reduced cell proliferation. In summary, the results demonstrated that non-cytotoxic cationic THCpSiNPs are promising vehicles for therapeutic siRNA delivery. Refereed/Peer-reviewed