High‐Pressure Nebulization as Application Route for the Peritoneal Administration of siRNA Complexes

Abstract

Peritoneal carcinomatosis is a severe form of cancer in the abdomen, currently treated with cytoreductive surgery and intravenous chemotherapy. Recently, nebulization has been proposed as a less invasive strategy for the local delivery of chemotherapeutic drugs. Also, RNA interference has been considered as a potential therapeutic approach for treatment of cancer. In this study, Lipofectamine RNAiMAX/siRNA complexes and cyclodextrin/siRNA complexes are evaluated before and after nebulization. Nebulization of the siRNA complexes does not significantly lower transfection efficiency when compared to non‐nebulized complexes. After incubation in ascites fluid, however, the cyclodextrin/siRNA complexes show a drastic decrease in transfection efficiency. For the Lipofectamine RNAiMAX/siRNA complexes, this decrease is less pronounced. It is concluded that nebulization is an interesting technique to distribute siRNA complexes into the peritoneal cavity, providing the complexes are stable in ascites fluid which might be present in the peritoneal cavity.

Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular Vector Design for Effective Gene Delivery

“…For practical reasons, we have chosen cyclomaltoheptaose (βCD) as the basic core to test the gemini‐type preorganization strategy for molecular vector elaboration; nevertheless, the synthetic methods are general and can be easily extended to other native CD representatives. Approaches allowing the installation of polycationic clusters at either the primary or the secondary rim of the CD core have been previously reported . The first arrangement, involving selective functionalization of the sterically more accessible primary hydroxyl groups, bears advantages in terms of simplicity and has been preferred in this work.…”

“…Approachesa llowing the installation of polycationic clusters at either the primary or the secondary rim of the CD core have been previously reported. [23][24][25][26][27][28][29][30][71][72][73] The first arrangement, involvings elective functionalization of the sterically more accessible primary hydroxyl groups,b ears advantages in terms of simplicity andh as been preferred in this work. Dimerizationc an then be effected through single-point differentiation at aprimary or asecondary position.I na ny event, the axial C 7 symmetry of the cyclooligosaccharide is lost.…”

“…[9][10][11][12][13] Further developmentso fa ccurates ynthetic manipulation [14] and (bio)orthogonal click-chemistry methodologies [15][16][17] have enabled the access to single-isomer,n anometric-sized molecules having ap ersistent topology and ap re-oriented pattern of functional groups, generally termed molecular nanoparticles, with surgical precision. [18][19][20] Ab attery of single-isomer3 Dd isplays tailored towards nucleic acid complexation, targeting, and delivery has thus been produced, [21,22] examples record on covering cyclodextrin (CD), [23][24][25][26][27][28][29][30] calixarene, [31][32][33][34][35][36] macrocyclic peptides, [37][38][39][40] fullerene, [41][42][43][44] pillarene, [45][46][47] or cyclotrehalanp latforms. [48,49] These studies have focused on the influence of the molecular architecture of the vectoro nt he self-assembling and the nucleic acid delivery capabilities; however, none of them has pursued shape control of the vector-nucleic acid nanoparticles for the systematic study of its role fort he transfection efficiency.…”

Pressurized intraperitoneal aerosol chemotherapy: a review of the introduction of a new surgical technology using the IDEAL framework

“…Overall, the search identified: 23 stage 0 studies; 18 stage 1 studies and two protocol papers for stage 1 studies; 25 stage 2a studies, one protocol paper and five trial registrations (NCT01854255, NCT02735928, NCT03246321, NCT02604784 and NCT03124394) for stage 2a studies; six stage 2b studies and three protocol papers for stage 2b studies; and three protocol papers for stage 3 studies. Fig .…”

From Polymers to Functional Biomaterials

“…While this process did not alter transfection efficiencies, the presence of ascites fluid reduces substantially the efficiency of cationic cyclodextrine based siRNA formulations. In contrast, the effect is much less pronounced for lipofectamine‐based siRNA polyplexes, which underlines on the one hand the importance of the cationic polymer and on the other the potential of high‐pressure nebulization for an application in the peritoneal cavity …”