Chitosan caged liposomes for improving oral bioavailability of rivaroxaban: in vitro and in vivo evaluation.

In this study, chitosan (CS) caged classic liposomes (CLs) and flexible liposomes (FLs) were developed to enhance the oral bioavailability of rivaroxaban (RVX) in the fasted condition. The prepared formulations were subjected to physicochemical characterization included: FTIR, DSC, zeta potential, particle size, polydispersity index, entrapment efficiency, in vitro dissolution, and transmission electron microscope imaging. The selected formulation (RVX-TFL2) composed of PL S100/Tween 80 (85/15% w/w) and coated with CS solution in the strength of (0.2% w/v) had a particle size of 105.67 nm, a zeta potential of +5.67 mV and EE of 96.07%. Compared to RXV suspension, the pharmacokinetic parameters (C max, AUC0-24, and AUC0-∞) of RVX-TFL2 showed no statistically significant difference (P > 0.05) in the fasted and fed test animals. Besides, RVX bioavailability with RVX-TFL2 was improved by 59.66% and 26.97% in the fed and fasted states, respectively, compared to RVX suspension in the fed state. The result highlighted the efficacy of the prepared liquid formulation comprising CS coated liposomes in improving the oral bioavailability of RVX regardless of the fed state. Moreover, the studied liquid formulation could be utilized in developing a liquid dosage form that might be useful as a pediatric formulation of RVX.

Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors.

Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14) could have a potential interest in delivery of anti-cancer agents to tumor cells. Attachment of SST to different nano-carriers e.g. polymeric nanoparticles is limited due to the difficulty of interaction between SST itself and those nano-carriers. Furthermore, the instability problems associated with the final formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive and negative charge of SST and citrate-AuNPs could be considered a new technique to get stable non-aggregated AuNPs coated with SST. Different analyses techniques have been performed to proof the principle of coating between AuNPs and SST. Furthermore, cellular uptake studies on HCC-1806, HELA and U-87 cell lines has been investigated to show the ability of AuNPs coated SST to enter the cells via SST receptors. Dynamic light scattering (DLS) indicated a successful coating of SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of AuNPs with SST. Cellular uptake studies on HCC-1806, HELA and U-87 cell lines showed that the number of AuNPs-SST per cell is signiflcantly higher compared to citrate-AuNPs when quantified using inductively coupled plasma spectroscopy. Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor-specific binding. In conclusion, AuNPs could be attached to SST via adsorption to get stable AuNPs coated SST. This new formulation has a potential to target SST receptors localized in many normal and tumor cells.

Layer-by-layer coated gold nanoparticles: size-dependent delivery of DNA into cells.

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size-dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer-by-layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC(50) value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.

Layer-by-layer assembled gold nanoparticles for siRNA delivery.

Although uptake into cells is highly complex and regulated, heterogeneous particle collectives are usually employed to deliver small interfering RNA (siRNA) to cells. Within these collectives, it is difficult to accurately identify the active species, and a decrease in efficacy is inherent to such preparations. Here, we demonstrate the manufacture of uniform nanoparticles with the deposition of siRNA on gold in a layer-by-layer approach, and we further report on the cellular delivery and siRNA activity as functions of surface properties.