Pharmaceutical Research

, Volume 33, Issue 2, pp 301–314 | Cite as

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

  • José Lopes-de-Araújo
  • Ana Rute Neves
  • Virgínia M. Gouveia
  • Catarina C. Moura
  • Cláudia Nunes
  • Salette Reis
Research Paper



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.


Two formulations containing oxaprozin were developed: NLCs with and without folate functionalization. In order to target the macrophages folate receptors, a DSPE-PEG2000-FA conjugate was synthesized and added to the NLCs.


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 μM. 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.


The developed nanoparticles enclose a great potential for oxaprozin oral administration with significant less gastric side-effects.


Caco-2 permeability study folate functionalization in vitro release study nanoparticles characterization oxaprozin 



Disteroylphosphatidylethanolamine-poly(ethylene glycol)2000-folic acid


Encapsulation efficiency

FA-NLCs + Oxa

DSPE-PEG2000-FA functionalized oxaprozin loaded nanostructured lipid carriers NLCs


DSPE-PEG2000-FA functionalized placebo nanostructured lipid carriers


Folate receptor




Loading capacity


Lipid nanoparticles


Nanostructured lipid carriers

NLCs Placebo

Non-functionalized placebo nanostructured lipid carriers

NLCs + Oxa

Non-functionalized oxaprozin loaded nanostructured lipid carriers


Non-steroidal Anti-inflammatory drugs




Solid lipid nanoparticles


Transepithelial electrical resistance



This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and by National Funds through FCT - Foundation for Science and Technology under the Pest-C/EQB/LA0006/2013 and FCOMP-01-0124-FEDER-3728. The work also received financial support from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07-0162-FEDER-000088. To all financing sources the authors are greatly indebted. JLA, ARN and CN also acknowledge the FCT for financial support through the Research grant PD/BI/105914/2014, PhD grant SFRH/BD/73379/2010 and Post-Doc Grant SFRH/BPD/81963/2011.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • José Lopes-de-Araújo
    • 1
  • Ana Rute Neves
    • 1
  • Virgínia M. Gouveia
    • 1
  • Catarina C. Moura
    • 1
  • Cláudia Nunes
    • 1
  • Salette Reis
    • 1
  1. 1.UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal

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