Baclofen-loaded solid lipid nanoparticles: Preparation, electrophysiological assessment of efficacy, pharmacokinetic and tissue distribution in rats after intraperitoneal administration
2011
Abstract Intrathecal
baclofenadministration is the reference treatment for spasticity of spinal or cerebral origin, but the risk of infection or catheter dysfunctions are important limits. To explore the possibility of alternative administration routes, we studied a new preparation comprising
solid lipid nanoparticles(SLN) incorporating
baclofen(
baclofen-SLN). We used SLN because they are able to give a sustained release and to target the CNS. Wistar rats were injected intraperitoneally with
baclofen-SLN or
baclofensolution (
baclofen-sol group) at increasing dosages. At different times up to 4 h, efficacy was tested by the
H-reflexand two scales evaluating sedation and motor symptoms due to spinal lesions. Rats were killed and
baclofenconcentration determined in blood and tissues. Physiological solution or unloaded SLN was used as controls. After
baclofen-SLN injection, the effect, consisting in a greater and earlier reduction of the H/M ratio than
baclofen-sol group and controls, was statistically significant from a dose of 5 mg/kg and was inversely correlated with dose. Clinical effect of
baclofen-SLN on both the behavioral scales was greater than that of
baclofen-sol and lasted until 4th hour. Compared with
baclofen-sol,
baclofen-SLN produced significantly higher drug concentrations in plasma from 2nd hour until 4th hour with a linear decrement and in the brain at all times. In conclusion, our study demonstrated the efficacy of a novel formulation of
baclofen, which exploits the advantages of SLN preparations. However, for clinical purposes, high
baclofenconcentrations in brain tissue and sedation may be unwanted effects, requiring further studies and optimization of dosages.
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