In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System

An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and sustained release. In this context, in situ solidifying organogels based on monoglycerides (MO), polyethylenimine (PEI), propylene glycol (PG) and tris buffer are an attractive strategy for intratumoral delivery of siRNA. In this study, precursor fluid formulation (PFF) composed of MO/PEI/PG/tris buffer at 7.85:0.65:76.5:15 (w/w/w/w) was used to deliver siRNA to tumor cells. The internal structure of the gel obtained from PFF was characterized using small angle X-ray scattering (SAXS). In addition, its ability to complex siRNA, protect it from degradation, and functionally deliver it to tumor cells was investigated. Moreover, in vivo gel formation following intratumoral injection was evaluated. The gel formed in excess water from PFF was found to comprise a mixture of hexagonal and cubic phases. The system was able to complex high amounts of siRNA, protect it from degradation, promote siRNA internalization, and induce gene silencing in vitro in a variety of tumor cell lines. Moreover, a gel formed in situ following intratumoral injection in a murine xenograft model. In conclusion, PFF is a potential delivery system for local and sustained delivery of siRNA to tumor tissue after intratumoral administration

Dynamics of encapsulated hepatitis B surface antigen:A combined neutron spectroscopy and thermo-analysis study

As a consequence of its ordered pore architecture, mesoporous SBA-15 offers new possibilities for incorporating biological agents. Considering its applicability in oral vaccination, which shows more beneficial features when compared with parenteral vaccines, SBA-15 is also seen as a very promising adjuvant to carry, protect, and deliver entrapped antigens. Recent studies have shown several remarkable features in the immunization of hepatitis B, a viral disease transmitted mainly through blood or serum transfer. However, the surface antigen of the hepatitis B virus, HBsAg, is too large to fit inside the SBA-15 matrix with mean pore diameter around 10 nm, thus raising the question of how SBA-15 can protect the antigen. In this work, thermal analysis combined with neutron spectroscopy allowed us to shed light on the interactions between HBsAg and SBA-15 as well as on the role that these interactions play in the efficiency of this promising oral vaccination method. This information was obtained by verifying how the dynamic behaviour of the antigen is modified under confinement in SBA-15, thus also establishing an experimental method for verifying molecular dynamics simulations