Lc-MS/MS Method Applied to Preclinical Pharmacokinetic Investigation of Olanzapine-Loaded Lipid-Core Nanocapsules

Dimer, Frantiescoli Anversa; Pigatto, Maiara Cássia; Pohlmann, Adriana Raffin; Costa, Teresa Cristina Tavares Dalla; Guterres, Sílvia Stanisçuaski

doi:10.5935/0100-4042.20140195

Cited by 1 publication

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“…AUC to the respective drug formulation AUC after 2.5 mg/kg i.v. dosing from a previous study (AUC OLA-LNC 1.998 g · h/ml and AUC OLA-FREE 0.884 g · h/ml) 21 the decrease in clearance is attributed to the lipid-core nanocapsules ability to prevent cellular uptake by macrophages due to the presence of polysorbate 80 coating. 31 After i.p.…”

Section: Discussionmentioning

confidence: 93%

“…(2.26-fold). 21 This finding indicates that the increased relative bioavailability is due to decreased clearance instead of increased absorption. Due to the absence of significant difference between OLA-LNC and OLA-FREE elimination rate constant, half-life and mean residence time, one can infer that nanoencapsulation of olanzapine produced an alteration on drug distribution to tissues pattern, causing and overall decrease in the volume of distribution.…”

Section: Discussionmentioning

confidence: 94%

“…These tissues were previously reported as the main organs which have the efflux protein P-gp. 42 21 The OLA-LNC prolonged the suppression of stereotyped behavior comparing with the OLA-FREE after a dose of 10 mg/kg via i.p. Psychotic behaviors were verified by the decrease in MA-induced stereotyped body movements.…”

Section: Discussionmentioning

confidence: 97%

“…dosing of OLA-LNC, confirming this hypothesis. 21 Drug delivery to the brain is limited by the blood-brain barrier (BBB), but the accurate mechanism responsible for changing the brain bioavailability remains unknown. 33 The mainly transport mechanisms in the BBB are related to the endocytosis, transcytosis, and modulation of tight junctions in the brain-blood vessel endothelial cells, which can be modified by the nanoparticle structure.…”

Section: Discussionmentioning

confidence: 99%

“…21 Bioanalytical method was developed on a LC Shimadzu system equipped with a SCL-10 A VP system controller, LC-10 AD VP pump, DGU-14A degasser, and CTO-10 AD VP column oven. The OLA separation was carried out on a reversed-phase Shim Pack (Shimadzu, Japan) CLC-C8 column (150 mm × 4 6 mm) preceded by a Czx8 guard column (5 m, 3 0 × 4 0 mm, Phenomenex ® ) kept at 30 C. The mobile phase consisted of acetonitrile: 5 mM ammonium acetate (70:30, v/v) and 0.1% acetic acid pumped at a flow rate of 0.45 ml/min.…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

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Nanoencapsulation Improves Relative Bioavailability and Antipsychotic Effect of Olanzapine in Rats

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et al. 2015

j biomed nanotechnol

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This study aimed to investigate the pharmacokinetics, tissue distribution and antipsychotic activity of olanzapine administered as free drug (OLA-FREE) or loaded into lipid-core nanocapsules (OLA-LNC). OLA-LNC were successfully developed with a particle size of 142 ± 4 nm and a zeta potential of -19.6 ± 0.6 mV. Pharmacokinetics and tissue distribution studies were carried out after the administration of free and nanoencapsulated olanzapine (10 mg/kg) by intraperitoneal route to male Wistar rats. Higher olanzapine concentrations and AUC(0-12 h) were found in plasma and tissues evaluated after the administration of OLA-LNC compared to the drug in the free form, resulting in a relative bioavailability of 226.7% in the plasma. As a result olanzapine loaded lipid-core nanocapsules presented pronounced and long-lasting effects on central nervous system. These nanocapsules (10 mg/kg, i.p.) significantly diminished the stereotyped behavior induced by D,L-amphetamine up to 12 hours whereas olanzapine free-form (10 mg/kg, i.p.) was effective during 03 hours only. Moreover, olanzapine loaded lipid-core nanocapsules (1.0 mg/kg, i.p.) have shown a marked sedative effect and also prevented the prepulse inhibition disruption induced by apomorphine at lower dose than olanzapine in free-form (2.5 mg/kg, i.p.). Herewith, we point to the nanoencapsulation as a strategy for reducing the concentration of olanzapine in pharmaceutical formulations.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 94%