Solid formulation of cell-penetrating peptide nanocomplexes with siRNA and their stability in simulated gastric conditions

JOURNAL OF CONTROLLED RELEASE

卷:162

Article

Ezzat, Kariem¹  Zaghloul, Eman M.²  Andaloussi, Samir E. L.^2,3  Lehto, Taavi⁴  El-Sayed, Ramy²  Magdy, Tarek¹  Smith, C. I. Edvard²  Langel, Ulo^1,4 

[1] Stockholm Univ, Dept Neurochem, S-10691 Stockholm, Sweden

[2] Karolinska Inst, Dept Lab Med, Huddinge, Sweden

[3] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

[4] Univ Tartu, Inst Technol, Mol Biotechnol Lab, EE-50090 Tartu, Estonia

关键词: Cell penetrating peptide;    siRNA;    Solid formulation;    Acid stability;    Gastric fluid;   

DOI  :  10.1016/j.jconrel.2012.06.006

来源: Elsevier

【 摘 要 】

Cell-penetrating peptides (CPPs) are short cationic peptides that have been extensively studied as drug delivery vehicles for proteins, nucleic acids and nanoparticles. However, the formulation of CPP-based therapeutics into different pharmaceutical formulations and their stability in relevant biological environments have not been given the same attention. Here, we show that a newly developed CPP, PepFect 14 (PF14), forms non-covalent nanocomplexes with short interfering RNA (siRNA), which are able to elicit efficient RNA-interference (RNAi) response in different cell-lines. RNAi effect is obtained at low siRNA doses with a unique kinetic profile. Furthermore, the solid dispersion technique is utilized to formulate PF14/siRNA nanocomplexes into solid formulations that are as active as the freshly prepared nanocomplexes in solution. Importantly, the nanocomplexes are stable and active in mediating RNAi response after incubation with simulated gastric fluid (SGF) that is highly acidic. These results demonstrate the activity of PF14 in delivering and protecting siRNA in different pharmaceutical forms and biological environments. (c) 2012 Elsevier B.V. All rights reserved.

【 授权许可】

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