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- Title
Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects.
- Authors
Lopes-de-Araújo, José; Neves, Ana; Gouveia, Virgínia; Moura, Catarina; Nunes, Cláudia; Reis, Salette
- Abstract
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-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 μM. Permeability studies in Caco-2 cells shown that oxaprozin encapsulation did not interfered with oxaprozin permeability (around 0.8 × 10 cm/s in simulated intestinal fluid and about 1.45 × 10 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.
- Subjects
NONSTEROIDAL anti-inflammatory agents; NANOMEDICINE; DRUG side effects; PHARMACOKINETICS; PHARMACODYNAMICS; PHAGOCYTES
- Publication
Pharmaceutical Research, 2016, Vol 33, Issue 2, p301
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-015-1788-x