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.

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.

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The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a nonsteroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64-7.75) and gel strength (15.5-65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72-92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.

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The delivery of nucleic acids to mammalian cells requires a potent particulate carrier system. The physicochemical properties of the used particles, such as size and surface charge, strongly influence the cellular uptake and thereby the extent of the subsequent biological effect. However the knowledge of this process is still fragmentary because heterogeneous particle collectives are applied. Therefore we present a strategy to synthesize carriers with a highly specific appearance on the basis of gold nanoparticles (AuNPs) and the Layer-by-Layer (LbL) technique. The LbL method is based on the alternate deposition of oppositely charged (bio-)polymers, in our case poly(ethylenimine) and nucleic acids. The size and surface charge of those particles can be easily modified and accordingly systematic studies on cellular uptake are accessible.

Although being a benign lesion, Warts can affect the quality of life by causing discomfort, disfigurement, and social embarrassment besides the tendency to spread.Cutaneous wart treatment faces many challenges as the development of an antiviral drug that can eradicate the human papilloma virus (HPV) is difficult. This clinical study aimed to assess the efficacy and safety of intralesional combined furosemide and digoxin in the treatment of multiple cutaneous warts. This double blinded randomized clinical trial included 80 adult patients with multiple cutaneous warts (≥2 warts) who were randomized into two groups, Group I (40 patients) treated with intralesional combined furosemide and digoxin and Group II (40 patients) who were treated with intralesional normal saline solution as a control group, weekly till improvement or for maximum five sessions. Clinical and dermoscopic evaluation at baseline, every session, and monthly for 6 months after the last session to detect any recurrence was performed. Complete wart clearance was observed in 92.5% of patients in the intralesional combined furosemide and digoxin group (Group I) compared with 10.0% in saline group (Group II), with highly statistically significant difference (Pvalue = 0.000). Pain during injection in 95.0% and 45.0% of patients in Group I and Group II respectively, treatment group was superior compared to control group.Intralesional injection of combined furosemide and digoxin can be a safe and effective treatment option in multiple cutaneous warts with minimal side effects in this study.