POLOXAMER 188 FUNCTIONALIZED EUDRAGIT RS-NANOCARRIERS AS A NOVEL STRATEGY FOR ENHANCING LOPERAMIDE CENTRAL NERVOUS SYSTEM BIODISTRIBUTION AND REDUCING PROTEOTOXIC STRESS

PONCE MF; CONSTANTIN MF; CATALÁN-FIGUEROA J; MONTIVERO A

Evento Virtual

Congreso; Reunión Anual de Sociedades de Biociencias. SAIC, SAI, SAFIS; 2020

Brain drug delivery current strategies are of wide scientific interest, mainly for the presence of the blood-brain barrier (BBB). Forthat matter, we have developed a nanotechnology-based deliverysystem for brain targeting, after its oral administration. Loperamidewas chosen since it does not cross the BBB, but exhibits anti-inflammatory activity, along with its mu-opioid-mediated analgesic effects, and non-mu-receptor associated neuroprotective properties,thus having potential advantages over morphine. Therefore, in thiswork, we evaluated the capacity of nanocarriers of Eudragit® RS (ERS) covered with poloxamer 188 (P188) and loaded with loperamide (NP-Lop), for crossing the BBB and reduce protein oxidativestress. Methods: Central biodistribution was assessed by evaluating NP-Lop supraspinal analgesic effects in rats naive submitted tothe Hot Plate Test, after its oral and intraperitoneal administration.Protein oxidative stress was measure in prefrontal cortex (PFC) ofrats submitted to traumatic brain injury (TBI), by advance oxidativeprotein products (AOPP) colorimetric assay, after NP-Lop intravenous administration. Confidence interval was set at 95%; statisticalanalysis was performed by t-student comparison or ANOVA andTukey test. Results: NP-Lop increased maximum possible effect inthe Hot Plate test at 30 min, 2 and 24 h after both, ip and vo NP-Lopadministration, in about 20 and 60-fold regarding loperamide in solution (Lop/Sol). In addition, NP-Lop reduce AOPP in about 6.7-foldregarding TBI. Conclusion: NP-Lop enhance loperamide CNS biodistribution, and reduces AOPP in a TBI rat model. Finally, the nanocarriers synthesized are potentially a nanopharmaceutical form thatmay enhance gastrointestinal absorption of drugs like loperamide.