@article {16161,
	title = {Nano-in-Micro Sildenafil Dry Powder Formulations for the Treatment of Pulmonary Arterial Hypertension Disorders: The Synergic Effect of POxylated Polyurea Dendrimers, PLGA, and Cholesterol},
	volume = {37},
	year = {2020},
	note = {n/a},
	month = {2020},
	pages = {1900447},
	abstract = {<p>Abstract POXylated polyurea dendrimer nanoparticles (PUREG4OOx48) are loaded with sildenafil (SDF) by a supercritical carbon dioxide{\textendash}assisted (scCO2) impregnation. Further supercritical CO2-assisted spray drying (SASD) leads to hybrid nano-in-micro dry powder formulations that are investigated aiming at efficient pulmonary delivery of SDF in pulmonary arterial hypertension treatment. This is the first report of the production of poly(D,L-lactide-co-glycolide)-cholesterol (PLGA-Chol) microparticles processed by SASD. The optimized formulation of nano-in-microparticles is composed of PLGA, Chol, and PUREG4OOx48, loaded with SDF solutions in a 77:23 ratio (PLGA-Chol:dendrimer, w/w). The dry powders are fully characterized and found to be highly biodegradable and biocompatible, and the SDF release profile evaluates under different pH values. The median mass average diameter (MMAD) of the nano-in-micro systems varies between 2.57 and 5 {\textmu}m and the fine particle fraction (FPF) between 36\% and 29\% for PUREG4OMeOx48[PLGA-Chol] and PUREG4OEtOx48[PLGA-Chol], respectively. The data validate the potential use of these new formulations in inhalation therapy. In vitro studies are also carried out in order to evaluate the effect of the free drug in cell viability and formulations cytotoxicity.</p>
},
	isbn = {0934-0866},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/ppsc.201900447},
	author = {Rita B. Restani and Rita F. Pires and Pedro V. Baptista and Alexandra R. Fernandes and Casimiro, Teresa and Vasco D.B. Bonif{\'a}cio and Aguiar-Ricardo, Ana}
}
