Impacts of particle shapes on the oral delivery of drug nanocrystals: Mucus permeation, transepithelial transport and bioavailability.
J Control Release
; 307: 64-75, 2019 08 10.
Article
en En
| MEDLINE
| ID: mdl-31207275
For drug nanocrystals (NCs), particle shapes can affect aqueous solubility, dissolution rate and oral bioavailability. However, the effects of particle shapes on the transport of NCs across the intestinal barriers remain unclear. In the present study, spherical, rod-shaped and flaky NCs (SNCs, RNCs, and FNCs) were prepared and characterized. Meanwhile, fluorescence resonance energy transfer molecules were used to track the fate of intact NCs. Results showed that particle shapes had great influences on the mucus permeation, cellular uptake and transmembrane transport of NCs, and RNCs exhibited the best absorption efficiency. Besides, we found that endoplasmic reticulum/Golgi and Golgi/plasma membrane pathways might be involved in the transcytosis and exocytosis of NCs. Moreover, the oral bioavailability study showed that AUC0-24h of RNCs was 1.44-fold and 1.8-fold higher than that of SNCs and FNCs, respectively. Collectively, these results provided compelling evidences that RNCs could potentially improve the absoption efficacy of NCs in oral delivery. Our findings give deep insights into the impacts of particle shapes on the oral absoption of NCs and provide valuable knowledge for rational design of optimized NCs for oral drug delivery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lovastatina
/
Inhibidores de Hidroximetilglutaril-CoA Reductasas
/
Nanopartículas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos