Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Lopes de Araujo, J (Author) Other; Neves, AR (Author) Other; Gouveia, VM (Author) Other; Moura, CC (Author) Other; Nunes, C (Author) Other; Reis, S (Author) FFUP

Journal

Title: Pharmaceutical Research

ISSN: 0724-8741

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00G-NBV

Abstract (EN): Purpose: Nanostructured Lipid Carriers (NLCs) loading oxaprozin were developed to address an effective drug packaging and targeted delivery, improving the drug pharmacokinetics and pharmacodynamics properties and avoiding the local gastric side-effects. Macrophages actively phagocyte particles with sizes larger than 200 nm and, when activated, over-express folate beta receptors - features that in the case of this work constitute the basis for passive and active targeting strategies. Methods: Two formulations containing oxaprozin were developed: NLCs with and without folate functionalization. In order to target the macrophages folate receptors, a DSPE-PEG<inf>2000</inf>-FA conjugate was synthesized and added to the NLCs. Results: These formulations presented a relatively low polydispersity index (approximately 0.2) with mean diameters greater than 200 nm and zeta potential inferior to ¿40 mV. The encapsulation efficiency of the particles was superior to 95% and the loading capacity was of 9%, approximately. The formulations retained the oxaprozin release in simulated gastric fluid (only around 10%) promoting its release on simulated intestinal fluid. MTT and LDH assays revealed that the formulations only presented cytotoxicity in Caco-2 cells for oxaprozin concentrations superior to 100 ¿M. Permeability studies in Caco-2 cells shown that oxaprozin encapsulation did not interfered with oxaprozin permeability (around 0.8 × 10¿5 cm/s in simulated intestinal fluid and about 1.45 × 10¿5 cm/s in PBS). Moreover, in RAW 264.7 cells NLCs functionalization promoted an increased uptake over time mainly mediated by a caveolae uptake mechanism. Conclusions: The developed nanoparticles enclose a great potential for oxaprozin oral administration with significant less gastric side-effects. © 2015 Springer Science+Business Media New York

Language: English

Type (Professor's evaluation): Scientific