Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy

Drug Delivery

Paola Mura¹  Marzia Cirri¹  Natascia Mennini¹  Francesca Maestrelli¹  Lorenzo Di Cesare Mannelli²  Carla Ghelardini²  Lavinia Maestrini³ 

[1] Department of Chemistry, School of Human Health Sciences, University of Florence, Florence, Italy;Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Florence, Florence, Ital;Menarini Manufacturing Logistics and Services, Florence, Italy;

关键词: Nanostructured lipid carriers;    hydrochlorothiazide;    hypertension;    pediatric therapy;    Precirol®ATO5;   

DOI  :  10.1080/10717544.2018.1529209

来源: publisher

【 摘 要 】

The hydrochlorothiazide (HCT) low solubility and permeability give rise to limited and variable bioavailability; its low stability makes it difficult to develop stable aqueous liquid formulations; its low dose makes the achievement of a homogeneous drug distribution very difficult. Thus, the aim of this study was to investigate the effectiveness of a strategy based on the development of nanostructured lipid carriers (NLC) as an innovative oral pediatric formulation of HCT with improved therapeutic efficacy. The performance of various synthetic and natural liquid lipids was examined and two different preparation methods were employed, i.e. homogenization-ultrasonication (HU) and microemulsion (ME), in order to evaluate their influence on the NLC properties in terms of size, polydispersity index, ζ-potential, entrapment efficiency, gastric stability, and drug release properties. Precirol®ATO5 was used as solid lipid and Tween®80 and Pluronic®F68 as surfactants, formerly selected in a previous study focused on the development of HCT-solid lipid nanoparticles (SLNs). The presence of Pluronic®F68 did not allow ME formation. On the contrary, using Tween®80, the ME method enabled a higher entrapment efficiency than the HU. Regardless of the preparation method, NLCs exhibited great entrapment efficiency values clearly higher than previous SLNs. Moreover, NLC-ME formulations provided a prolonged release, which lasted for 6 h. In particular, NLC-ME containing Tween®20 as Co-Surfactant showed the best performances, giving rise to a complete drug release, never achieved with previous SLN formulations, despite their successful results. In vivo studies on rats confirmed these results, displaying their best diuretic profile. Moreover, all HCT-loaded NLC formulations showed higher stability than the corresponding SLNs.

【 授权许可】

CC BY