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Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

Wu N, Zhang X, Li F, Zhang T, Gan Y, Li J - Int J Nanomedicine (2015)

Bottom Line: Highly dispersed dry powders with diameters of 5-15 μm were produced.These powders showed effective siRNA protection and sustained release.The mucus-penetrating properties of the powders differed depending on their compositions.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.

ABSTRACT
Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

No MeSH data available.


Related in: MedlinePlus

Scanning electron microphotograph images.Notes: Images of 0.5% HEC (A), solutions of F1 (B), F2 (C), F3 (D), and F4 (E) powder carriers, 0.5% HEC after the addition of F1 (F), F2 (G), F3 (H), and F4 (I) powders (containing no nanoparticles), 0.5% HEC after the addition of F1 (J), F2 (K), F3 (L), and F4 (M) powder carriers solutions; scale bar: 100 μm. The arrows in G and K indicate the pore size of the network.Abbreviations: F, formulation; HEC, hydroxyethyl cellulose; HV, high voltage; Sem mag: scanning electron microscopy magnification; Vac, vacuum.
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f6-ijn-10-5383: Scanning electron microphotograph images.Notes: Images of 0.5% HEC (A), solutions of F1 (B), F2 (C), F3 (D), and F4 (E) powder carriers, 0.5% HEC after the addition of F1 (F), F2 (G), F3 (H), and F4 (I) powders (containing no nanoparticles), 0.5% HEC after the addition of F1 (J), F2 (K), F3 (L), and F4 (M) powder carriers solutions; scale bar: 100 μm. The arrows in G and K indicate the pore size of the network.Abbreviations: F, formulation; HEC, hydroxyethyl cellulose; HV, high voltage; Sem mag: scanning electron microscopy magnification; Vac, vacuum.

Mentions: In order to examine the changes in model gels exposed to these formulations intuitively, we observed the morphologies and structures of the freeze-dried samples. As shown in Figure 6, all of the samples exhibited cross-linked structures with randomly arranged fiber networks and different pore sizes. The observed structures of the powder carrier solutions provided possible explanations for the differences in the release of siRNA. F4 showed a network with a higher degree of cross-linking, resulting in more difficult release of the nanoparticles from the F4 network and thus a lower siRNA release rate. In contrast, the potential formation of an inter-polymer complex between F127 and HPMC contributed to a more regular honeycomb-like network with expanded pore sizes in F2 and F3, which might allow for easier release of nanoparticles.


Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

Wu N, Zhang X, Li F, Zhang T, Gan Y, Li J - Int J Nanomedicine (2015)

Scanning electron microphotograph images.Notes: Images of 0.5% HEC (A), solutions of F1 (B), F2 (C), F3 (D), and F4 (E) powder carriers, 0.5% HEC after the addition of F1 (F), F2 (G), F3 (H), and F4 (I) powders (containing no nanoparticles), 0.5% HEC after the addition of F1 (J), F2 (K), F3 (L), and F4 (M) powder carriers solutions; scale bar: 100 μm. The arrows in G and K indicate the pore size of the network.Abbreviations: F, formulation; HEC, hydroxyethyl cellulose; HV, high voltage; Sem mag: scanning electron microscopy magnification; Vac, vacuum.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554414&req=5

f6-ijn-10-5383: Scanning electron microphotograph images.Notes: Images of 0.5% HEC (A), solutions of F1 (B), F2 (C), F3 (D), and F4 (E) powder carriers, 0.5% HEC after the addition of F1 (F), F2 (G), F3 (H), and F4 (I) powders (containing no nanoparticles), 0.5% HEC after the addition of F1 (J), F2 (K), F3 (L), and F4 (M) powder carriers solutions; scale bar: 100 μm. The arrows in G and K indicate the pore size of the network.Abbreviations: F, formulation; HEC, hydroxyethyl cellulose; HV, high voltage; Sem mag: scanning electron microscopy magnification; Vac, vacuum.
Mentions: In order to examine the changes in model gels exposed to these formulations intuitively, we observed the morphologies and structures of the freeze-dried samples. As shown in Figure 6, all of the samples exhibited cross-linked structures with randomly arranged fiber networks and different pore sizes. The observed structures of the powder carrier solutions provided possible explanations for the differences in the release of siRNA. F4 showed a network with a higher degree of cross-linking, resulting in more difficult release of the nanoparticles from the F4 network and thus a lower siRNA release rate. In contrast, the potential formation of an inter-polymer complex between F127 and HPMC contributed to a more regular honeycomb-like network with expanded pore sizes in F2 and F3, which might allow for easier release of nanoparticles.

Bottom Line: Highly dispersed dry powders with diameters of 5-15 μm were produced.These powders showed effective siRNA protection and sustained release.The mucus-penetrating properties of the powders differed depending on their compositions.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.

ABSTRACT
Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

No MeSH data available.


Related in: MedlinePlus