Title |
Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects
|
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Published in |
Pharmaceutical Research, September 2015
|
DOI | 10.1007/s11095-015-1788-x |
Pubmed ID | |
Authors |
José Lopes-de-Araújo, Ana Rute Neves, Virgínia M. Gouveia, Catarina C. Moura, Cláudia Nunes, Salette Reis |
Abstract |
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. |
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Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 7 | 18% |
Student > Doctoral Student | 3 | 8% |
Student > Bachelor | 3 | 8% |
Researcher | 2 | 5% |
Other | 3 | 8% |
Unknown | 11 | 29% |
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Other | 6 | 16% |
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