Proof of concept studies for siRNA delivery by nonionic surfactant vesicles: in vitro and in vivo evaluation of protein knockdown

Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV drug. Niosomes were formulated by conventional thin film hydration technique with different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The formulated niosomes were found spherical in shape, ranging from 2.95 μm to 10.91 μm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol : dicetyl phosphate with each grade of span were found to have higher entrapment efficiencies, which were further selected forin vitroandin vivostudies. Vesicles formulated with sorbitan monostearate were found to have maximum drug release (99.091%) at the end of 24 hours and followed zero order release kinetics. The results ofin vivostudy revealed that the niosomes significantly enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The average relative bioavailability of niosomes in relation to plane drug solution was found to be 2.58, indicating more than twofold increase in oral bioavailability of TDF. Significant increase in mean residential time (MRT) was also found, reflecting release retarding efficacy of the vesicles. In conclusion, niosomes could be a promising delivery for TDF with improved oral bioavailability and prolonged release profiles.

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Statistically designed nonionic surfactant vesicles for dermal delivery of itraconazole: Characterization and in vivo evaluation using a standardized Tinea pedis infection model

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2014.06.030 ◽

2014 ◽

Vol 472 (1-2) ◽

pp. 224-240 ◽

Cited By ~ 11

Author(s):

Neeraj Kumar ◽

Shishu Goindi

Keyword(s):

Nonionic Surfactant ◽

Tinea Pedis ◽

Infection Model ◽

In Vivo Evaluation ◽

Surfactant Vesicles ◽

Nonionic Surfactant Vesicles ◽

Dermal Delivery

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In vivo Evaluation and Alzheimer’s Disease Treatment Outcome of siRNA Loaded Dual Targeting Drug Delivery System

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190204141046 ◽

2019 ◽

Vol 20 (1) ◽

pp. 56-62 ◽

Cited By ~ 1

Author(s):

Chi Zhang ◽

Zhichun Gu ◽

Long Shen ◽

Xianyan Liu ◽

Houwen Lin

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Treatment Outcome ◽

Neuroprotective Effect ◽

Sirna Delivery ◽

Repeated Administration ◽

Spatial Learning And Memory ◽

In Vivo Evaluation

Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance in the target quadrant. Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good candidate for AD targeting siRNA delivery.

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