Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. / Jensen, Ditte Marie Krohn; Jensen, Linda Boye; Koocheki, Saeid; Cun, Dongmei; Nielsen, Hanne Mørck; Foged, Camilla; Bengtson, Lasse.

I: Journal of Controlled Release, Bind 157, Nr. 1, 2012, s. 141-148.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Jensen, DMK, Jensen, LB, Koocheki, S, Cun, D, Nielsen, HM, Foged, C & Bengtson, L 2012, 'Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA', Journal of Controlled Release, bind 157, nr. 1, s. 141-148. https://doi.org/10.1016/j.jconrel.2011.08.011

APA

Jensen, D. M. K., Jensen, L. B., Koocheki, S., Cun, D., Nielsen, H. M., Foged, C., & Bengtson, L. (2012). Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. Journal of Controlled Release, 157(1), 141-148. https://doi.org/10.1016/j.jconrel.2011.08.011

Vancouver

Jensen DMK, Jensen LB, Koocheki S, Cun D, Nielsen HM, Foged C o.a. Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. Journal of Controlled Release. 2012;157(1):141-148. https://doi.org/10.1016/j.jconrel.2011.08.011

Author

Jensen, Ditte Marie Krohn ; Jensen, Linda Boye ; Koocheki, Saeid ; Cun, Dongmei ; Nielsen, Hanne Mørck ; Foged, Camilla ; Bengtson, Lasse. / Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. I: Journal of Controlled Release. 2012 ; Bind 157, Nr. 1. s. 141-148.

Bibtex

@article{0d3bd844be3044c388949aedbca3ea2b,
title = "Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA",
abstract = "Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local delivery of biologically active siRNA directly to the lung tissue.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Jensen, {Ditte Marie Krohn} and Jensen, {Linda Boye} and Saeid Koocheki and Dongmei Cun and Nielsen, {Hanne M{\o}rck} and Camilla Foged and Lasse Bengtson",
year = "2012",
doi = "10.1016/j.jconrel.2011.08.011",
language = "English",
volume = "157",
pages = "141--148",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA

AU - Jensen, Ditte Marie Krohn

AU - Jensen, Linda Boye

AU - Koocheki, Saeid

AU - Cun, Dongmei

AU - Nielsen, Hanne Mørck

AU - Foged, Camilla

AU - Bengtson, Lasse

PY - 2012

Y1 - 2012

N2 - Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local delivery of biologically active siRNA directly to the lung tissue.

AB - Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local delivery of biologically active siRNA directly to the lung tissue.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.jconrel.2011.08.011

DO - 10.1016/j.jconrel.2011.08.011

M3 - Journal article

C2 - 21864597

VL - 157

SP - 141

EP - 148

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -

ID: 36103747