Poloxamer 188 functionalized Eudragit RS-nanocarriers as a novel strategy for enhancing loperamide Central Nervous System biodistribution and reducing proteotoxic stress.

CATALAN-FIGUEROA, JOHANNA; PONCE BETI MF; CONSTANTIN MF; AGUSTIN MONTIVERO; SILVERO MJ; BECERRA MC; PÉREZ, MARIELA F.

Congreso; Reunión ANual de SOciedades de BIociencias SAIC, SAI, SAFIS, 2020. LXV Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

SAIC

Brain drug delivery current strategies are of wide scientific interest, mainly for the presence of the blood-brain barrier (BBB). For that matter, we have developed a nanotechnology-based delivery system for brain targeting, after its oral (vo) or intraperitoneal (ip) administration. Loperamide (Lop) exhibits anti-inflammatory activity, along with its mu-opioid-mediated analgesic effects and non-mu-receptor associated neuroprotective properties. Then Lop may have potential therapeutic advantages over morphine, although it is not used for those purposes because its poor vo absorption and its inability to cross the BBB. Therefore, in this work, we have evaluated the capacity of nanocarriers of Eudragit® RS covered with poloxamer 188 loaded with Lop (NP-Lop) for crossing the BBB and reduce protein oxidative stress. Methods: central biodistribution was assessed by evaluating NP-Lop supraspinal analgesic effects in naive rats submitted to the Hot Plate Test, after its vo and ip administration. Protein oxidative stress was measured in prefrontal cortex (PFC) of rats submitted to traumatic brain injury (TBI), by advance oxidative protein products (AOPP) colorimetric assay, after NP-Lop or Lop in solution (Lop/Sol) intravenous administration. Confidence interval was set at 95%; statistical analysis was performed by t-student comparisson or ANOVA and Tukey test. Results: NP-Lop increased analgesic effects in the Hot Plate test at 30 min, 2 and 24 h after both, ip and vo administration, in about 20 and 60-fold compared to Lop/Sol administration. In addition, NP-Lop reduced AOPP in about 6.7-fold regarding Lop/Sol. Conclution: NP-Lop enhances loperamide central nervous system (CNS) biodistribution and reduces AOPP in a TBI rat model. These novel nanocarriers could represent a potential nanopharmaceutical formulation for both, enhancing gastrointestinal absorption and facilitating the BBB permeability of drugs with pharmacological value in CNS.