Development of a Novel Method for Formulating Stable siRNA-Loaded Lipid Particles for In vivo Use

Abstract

This paper describes a simple method of formulating PEGylated siRNA-loaded lipid particles. Given the ease of preparation, long term stability and favourable characteristics for in vivo delivery, our work represents an advance in lipid formulation of siRNA for in vivo use.

Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models

“…administration. 7 In addition to the simplicity of the preparation procedure, we also showed that these freeze-dried, lipidbased, formulations are highly stable even after storage at room temperatures for 1 month.…”

“…We, therefore, subsequently evaluated the feasibility of delivering siRNA to solid cervical cancer tumours using our previously reported HFDM-formulated PEGylated lipidic system. 7 Serum stability and pharamacokinetic profiles of HFDM-formulated nucleic acid-loaded lipid particles We have previously established the ability of HFDM-formulated lipid particles to accumulate in subcutaneous tumours after systemic administration. 7 Here, we aimed to characterize these particles further via assessing their serum stability as well as their pharmacokinetic profile.…”

“…7 Serum stability and pharamacokinetic profiles of HFDM-formulated nucleic acid-loaded lipid particles We have previously established the ability of HFDM-formulated lipid particles to accumulate in subcutaneous tumours after systemic administration. 7 Here, we aimed to characterize these particles further via assessing their serum stability as well as their pharmacokinetic profile. As shown in Figure 3a, in contrast to the nonPEGylated lipoplexes in which large aggregates (43 mm) formed immediately after the addition of serum, the size of the HFDMformulated particles remained constant, even after prolonged incubation with serum at 37 1C (Figure 3b).…”

“…As a significant amount of these particles accumulated in the liver after i.v. administration, 7 we performed an alanine transaminase enzyme test to detect any obvious adverse effect of these particles in the liver. The result showed that the administration of either 20 or 40 mg of siRNA-entrapped HFDM-formulated lipid particles gave no elevation of alanine transaminase enzyme activity at 24 h compared with vehicle-treated mice (Figure 4c).…”

Nanoscale Small Interfering RNA Delivery Systems For Personalized Cancer Therapy

“…Alternatively, nanoparticles can be prepared without an extrusion step under conditions where the lipid concentrations fall below their solubilities in the mixed solvents, leading to formation of liposomes with particle diameter <200 nm without any needs of extrusion [43]. In addition, some investigators have reported preparation of siRNA-loaded liposomes by using a freeze-dry procedure [45], although this procedure may result in unintended structural alterations [46]. Moreover, to package siRNA, some groups utilized significantly more complex liposome formulations.…”