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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

The viscosity of the solution formulations (before spray-drying), the sizes of the powders, and the particle size distribution of the reconstituted nanoparticles from the dry powders.Notes: Mean ± SD; n=3.Abbreviations: CS, chitosan; E80, Lipoid E80; F, formulation; NA, not applicable.
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f1-ijn-10-5383: The viscosity of the solution formulations (before spray-drying), the sizes of the powders, and the particle size distribution of the reconstituted nanoparticles from the dry powders.Notes: Mean ± SD; n=3.Abbreviations: CS, chitosan; E80, Lipoid E80; F, formulation; NA, not applicable.

Mentions: The formulations were designed based on the viscosities of the solutions prior to spray-drying. Viscosity measurement revealed that in the low concentration range, the viscosity of F127 was equal to that of HPMC at a F127:HPMC ratio of 4:1, w/w (data not shown). Thus, the compositions of the formulations were designed as shown in Table 1. As expected, these four formulations showed close viscosity values (Figure 1).


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)

The viscosity of the solution formulations (before spray-drying), the sizes of the powders, and the particle size distribution of the reconstituted nanoparticles from the dry powders.Notes: Mean ± SD; n=3.Abbreviations: CS, chitosan; E80, Lipoid E80; F, formulation; NA, not applicable.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-5383: The viscosity of the solution formulations (before spray-drying), the sizes of the powders, and the particle size distribution of the reconstituted nanoparticles from the dry powders.Notes: Mean ± SD; n=3.Abbreviations: CS, chitosan; E80, Lipoid E80; F, formulation; NA, not applicable.
Mentions: The formulations were designed based on the viscosities of the solutions prior to spray-drying. Viscosity measurement revealed that in the low concentration range, the viscosity of F127 was equal to that of HPMC at a F127:HPMC ratio of 4:1, w/w (data not shown). Thus, the compositions of the formulations were designed as shown in Table 1. As expected, these four formulations showed close viscosity values (Figure 1).

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