| Autor: |
Katas H; Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia , Jalan Raja Muda Abdul Aziz, Kuala Lumpur , Malaysia., Abdul Ghafoor Raja M, Ee LC |
| Jazyk: |
angličtina |
| Zdroj: |
Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2014 Nov; Vol. 40 (11), pp. 1443-50. Date of Electronic Publication: 2013 Aug 21. |
| DOI: |
10.3109/03639045.2013.828222 |
| Abstrakt: |
Recently, a newly discovered Dicer-substrate siRNA (DsiRNA) demonstrates higher potency in gene silencing than siRNA but both suffer from rapid degradation, poor cellular uptake and chemical instability. Therefore, Tat-peptide was exploited to protect and facilitate their delivery into cells. In this study, Tat-peptide was complexed with siRNA or DsiRNA through simple complexation. The physicochemical properties (particle size, surface charge and morphology) of the complexes formed were then characterized. The ability of Tat-peptide to carry and protect siRNA or DsiRNA was determined by UV-Vis spectrophotometry and serum protection assay, respectively. Cytotoxicity effect of these complexes was assessed in V79 cell line. siRNA-Tat complexes had particle size ranged from 186 ± 17.8 to 375 ± 8.3 nm with surface charge ranged from -9.3 ± 1.0 to +13.5 ± 1.0 mV, depending on the Tat-to-siRNA concentration ratio. As for DsiRNA-Tat complexes, the particle size was smaller than the ones complexed with siRNA, ranging from 176 ± 8.6 to 458 ± 14.7 nm. Their surface charge was in the range of +27.1 ± 3.6 to +38.1 ± 0.9 mV. Both oligonucleotide (ON) species bound strongly to Tat-peptide, forming stable complexes with loading efficiency of more than 86%. These complexes were relatively non cytotoxic as the cell viability of ∼90% was achieved. In conclusion, Tat-peptide has a great potential as siRNA and DsiRNA vector due to the formation of stable complexes with desirable physical characteristics, low toxicity and able to carry high amount of siRNA or DsiRNA. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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