Abstract
The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140 to 298 nm, and encapsulation efficiency ranging from 52 to 89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 149-157 |
| Number of pages | 9 |
| Journal | International Journal of Pharmaceutics |
| Volume | 454 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2013 |
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Keywords
- BeWo cells
- Congenital adrenal hyperplasia
- Dexamethasone
- Nanoparticles
- Placenta
- Pregnancy
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Preparation, characterization,and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model. / Ali, Hazem; Kalashnikova, Irina; White, Mark; Sherman, Michael; Rytting, Erik.
In: International Journal of Pharmaceutics, Vol. 454, No. 1, 2013, p. 149-157.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preparation, characterization,and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model
AU - Ali, Hazem
AU - Kalashnikova, Irina
AU - White, Mark
AU - Sherman, Michael
AU - Rytting, Erik
PY - 2013
Y1 - 2013
N2 - The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140 to 298 nm, and encapsulation efficiency ranging from 52 to 89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia.
AB - The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140 to 298 nm, and encapsulation efficiency ranging from 52 to 89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia.
KW - BeWo cells
KW - Congenital adrenal hyperplasia
KW - Dexamethasone
KW - Nanoparticles
KW - Placenta
KW - Pregnancy
UR - http://www.scopus.com/inward/record.url?scp=84884163096&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884163096&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2013.07.010
DO - 10.1016/j.ijpharm.2013.07.010
M3 - Article
C2 - 23850397
AN - SCOPUS:84884163096
VL - 454
SP - 149
EP - 157
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -