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Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice.

Hattori Y, Date M, Arai S, Kawano K, Yonemochi E, Maitani Y - J Pharm (Cairo) (2013)

Bottom Line: Although the sizes of all elastic liposomes prepared in this study were about 80-90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700-1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550-780 nm.Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution.These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.

ABSTRACT
We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80-90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700-1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550-780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

No MeSH data available.


Related in: MedlinePlus

The suppression of luciferase activity (a) and cytotoxicity (b) after siRNA transfection by elastic cationic liposomes. In (a), cationic lipoplexes were added to FL-SiHa cells at 50 nM siRNA. The luciferase assay was carried out 48 h after incubation of the lipoplexes. Statistical significance was evaluated by Student's t-test. *P < 0.05, **P < 0.01, and ***P < 0.001, compared with lipoplex of Cont siRNA. In (b), cytotoxicity was evaluated 48 h after transfection. In (a) and (b), each column represents the mean ± S.D. (n = 3).
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fig2: The suppression of luciferase activity (a) and cytotoxicity (b) after siRNA transfection by elastic cationic liposomes. In (a), cationic lipoplexes were added to FL-SiHa cells at 50 nM siRNA. The luciferase assay was carried out 48 h after incubation of the lipoplexes. Statistical significance was evaluated by Student's t-test. *P < 0.05, **P < 0.01, and ***P < 0.001, compared with lipoplex of Cont siRNA. In (b), cytotoxicity was evaluated 48 h after transfection. In (a) and (b), each column represents the mean ± S.D. (n = 3).

Mentions: Next, we investigated the silencing effects of luciferase mRNA and cytotoxicity in SiHa-Luc cells after transfection of the lipoplexes with Luc siRNA (Figures 2(a) and 2(b)). Although all formulations showed the suppression of luciferase activity without cytotoxicity, an increase of Tween 80 content (T15-liposome) decreased the silencing effect by elastic lipoplex. As a control, lipofectamine RNAiMax, a commercially available transfection reagent, induced strong suppression by siRNA transfection.


Transdermal Delivery of Small Interfering RNA with Elastic Cationic Liposomes in Mice.

Hattori Y, Date M, Arai S, Kawano K, Yonemochi E, Maitani Y - J Pharm (Cairo) (2013)

The suppression of luciferase activity (a) and cytotoxicity (b) after siRNA transfection by elastic cationic liposomes. In (a), cationic lipoplexes were added to FL-SiHa cells at 50 nM siRNA. The luciferase assay was carried out 48 h after incubation of the lipoplexes. Statistical significance was evaluated by Student's t-test. *P < 0.05, **P < 0.01, and ***P < 0.001, compared with lipoplex of Cont siRNA. In (b), cytotoxicity was evaluated 48 h after transfection. In (a) and (b), each column represents the mean ± S.D. (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590792&req=5

fig2: The suppression of luciferase activity (a) and cytotoxicity (b) after siRNA transfection by elastic cationic liposomes. In (a), cationic lipoplexes were added to FL-SiHa cells at 50 nM siRNA. The luciferase assay was carried out 48 h after incubation of the lipoplexes. Statistical significance was evaluated by Student's t-test. *P < 0.05, **P < 0.01, and ***P < 0.001, compared with lipoplex of Cont siRNA. In (b), cytotoxicity was evaluated 48 h after transfection. In (a) and (b), each column represents the mean ± S.D. (n = 3).
Mentions: Next, we investigated the silencing effects of luciferase mRNA and cytotoxicity in SiHa-Luc cells after transfection of the lipoplexes with Luc siRNA (Figures 2(a) and 2(b)). Although all formulations showed the suppression of luciferase activity without cytotoxicity, an increase of Tween 80 content (T15-liposome) decreased the silencing effect by elastic lipoplex. As a control, lipofectamine RNAiMax, a commercially available transfection reagent, induced strong suppression by siRNA transfection.

Bottom Line: Although the sizes of all elastic liposomes prepared in this study were about 80-90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700-1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550-780 nm.Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution.These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.

ABSTRACT
We developed elastic cationic liposomal vectors for transdermal siRNA delivery. These liposomes were prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid and sodium cholate (NaChol) or Tween 80 as an edge activator. When NaChol or Tween 80 was included at 5, 10, and 15% (w/w) into DOTAP liposomal formulations (C5-, C10-, and C15-liposomes and T5-, T10-, and T15-liposomes), C15- and T10-liposomes showed 2.4- and 2.7-fold-higher elasticities than DOTAP liposome, respectively. Although the sizes of all elastic liposomes prepared in this study were about 80-90 nm, the sizes of C5-, C10- and C15-liposome/siRNA complexes (lipoplexes) were about 1,700-1,800 nm, and those of T5-, T10-, and T15-lipoplexes were about 550-780 nm. Their elastic lipoplexes showed strong gene suppression by siRNA without cytotoxicity when transfected into human cervical carcinoma SiHa cells. Following skin application of the fluorescence-labeled lipoplexes in mice, among the elastic lipoplexes, C15- and T5-lipoplexes showed effective penetration of siRNA into skin, compared with DOTAP lipoplex and free siRNA solution. These data suggest that elastic cationic liposomes containing an appropriate amount of NaChol or Tween 80 as an edge activator could deliver siRNA transdermally.

No MeSH data available.


Related in: MedlinePlus