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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

Mucoadhesive properties of cy5-siRNA-loaded dry powders.Note: **P<0.01compared with F2–F4.Abbreviations: F, formulation; siRNA, small interfering RNA.
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f8-ijn-10-5383: Mucoadhesive properties of cy5-siRNA-loaded dry powders.Note: **P<0.01compared with F2–F4.Abbreviations: F, formulation; siRNA, small interfering RNA.

Mentions: The mucoadhesive properties of powders was investigated in an ex vivo experiment and operated on the rabbit vaginal explants. In order to simulate the biological flow through mucous membranes, citrate buffer solution (5 mM, pH 4.5) was used as a simulated fluid. Despite their equal viscosities, F1–F4 powders showed different mucoadhesive properties. The adherent fractions of these formulations ranged from approximately 56% for F1 to 85% for F4, which contained 0.25% HPMC (Figure 8). This stronger adhesion of F4 may reflect interactions between the carrier materials and mucus.


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)

Mucoadhesive properties of cy5-siRNA-loaded dry powders.Note: **P<0.01compared with F2–F4.Abbreviations: F, formulation; siRNA, small interfering RNA.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-5383: Mucoadhesive properties of cy5-siRNA-loaded dry powders.Note: **P<0.01compared with F2–F4.Abbreviations: F, formulation; siRNA, small interfering RNA.
Mentions: The mucoadhesive properties of powders was investigated in an ex vivo experiment and operated on the rabbit vaginal explants. In order to simulate the biological flow through mucous membranes, citrate buffer solution (5 mM, pH 4.5) was used as a simulated fluid. Despite their equal viscosities, F1–F4 powders showed different mucoadhesive properties. The adherent fractions of these formulations ranged from approximately 56% for F1 to 85% for F4, which contained 0.25% HPMC (Figure 8). This stronger adhesion of F4 may reflect interactions between the carrier materials and mucus.

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