Brain targeted lactoferrin coated lipid nanocapsules for the combined effects of apocynin and lavender essential oil in PTZ induced seizures
Apocynin (APO) is a plant derived antioxidant exerting specific NADPH oxidase inhibitory action substantiating its neuroprotective effects in various CNS disorders, including epilepsy. Due to rapid elimination and poor bioavailability, treatment with APO is challenging. Correspondingly, novel APO-loaded lipid nanocapsules (APO-LNC) were formulated and coated with lactoferrin (LF-APO-LNC) to improve brain targetability and prolong residence time.
Lavender oil (LAV) was incorporated into LNC as a bioactive ingredient to act synergistically with APO in alleviating pentylenetetrazol (PTZ)-induced seizures. The optimized LF-APO-LAV/LNC showed a particle size 59.7 ± 4.5 nm with narrow distribution and 6.07 ± 1.6mV zeta potential) with high entrapment efficiency 92 ± 2.4% and sustained release (35% in 72 h). Following subcutaneous administration, LF-APO-LAV/LNC brought about ⁓twofold increase in plasma AUC and MRT compared to APO. A Log BB value of 0.2 ± 0.14 at 90 min reflects increased brain accumulation.
In a PTZ-induced seizures rat model, LF-APO-LAV/LNC showed a Modified Racine score of 0.67 ± 0.47 with a significant increase in seizures latency and decrease in duration. Moreover, oxidant/antioxidant capacity and inflammatory markers levels in brain tissue were significantly improved. Histopathological and immunohistochemical assessment of brain tissue sections further supported these findings. The results suggest APO/LAV combination in LF-coated LNC as a promising approach to counteract seizures.
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Materials
Apocynin (4′-Hydroxy-3′-methoxyacetophenone) (APO) and Pentylenetetrazol (PTZ) were purchased from Sigma-Aldrich (St. Louis, MO). Labrafac® lipophile WL 1349 (caprylic-capric acid triglycerides; European Pharmacopeia, IVth, 2002) was obtained from Gattefossé SA (Saint-Priest, France). Kolliphor HS 15 (a mixture of free polyethylene glycol 660 and polyethylene glycol 660 hydroxystearate, European Pharmacopeia, IVth, 2002) was obtained from BASF (Ludwigshafen, Germany). Lipoid S100 (a soybean lecithin containing 94% of phosphatidylcholine) was obtained from Lipoïd GMBH (Ludwigshafen, Germany). Lactoferrin (LF) was obtained from Lactoferrin.co (Frankfurt, Germany). Span® 80 (sorbitan monooleate) was obtained from LobaChemie for Laboratory Reagents and Fine Chemicals (Mumbai, India). Lavender oil (Lavandula angustifolia aromatic 100% pure essential oil – steam extract) was obtained from Imtenan, Egypt. HPLC grade methanol was obtained from Thermo Fisher Scientific (Waltham, MA, USA). Ultracentrifugation concentration tubes (Sartorius™ Vivaspin6™, MWCO 100,000). Malondialdehyde (MDA) and Glutathione (GSH) kits (#E-BC-K030-M) were from Elabscience (Houston, Texas, USA). Superoxide Dismutase (SOD) (#ESOD-100) was purchased from BioAssay Systems (Hayward, California, USA). Rat TNF-α (#CSB-E11987r) and IL-6 ELISA kits (#CSB-E04640r) were from CUSABIO, Texas, USA. All other reagents were of analytical grade.
Youssef, J.R., Boraie, N.A., Ismail, F.A. et al. Brain targeted lactoferrin coated lipid nanocapsules for the combined effects of apocynin and lavender essential oil in PTZ induced seizures. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-024-01610-0
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