DEVELOPMENT AND ASSESSMENT OF A NEW NANOFORMULATION OF ANANDAMIDE WITH A PROMISSORY CARDIOVASCULAR THERAPEUTIC EFFECT�

SANZ, RAUL; RAMIREZ, D; KASSUHA, DIEGO; GIMENEZ, MARTIN; CAMARGO, A; YUNES, ROBERTO; MOCAYAR, FERES; GARCÍA, SEBASTIAN; MANUCHA, WALTER

Mendoza

Simposio; II Simposio Internacioal de Medicina Traslacional; 2019

DEVELOPMENT AND ASSESSMENT OF A NEW NANOFORMULATION OF ANANDAMIDEWITH A PROMISSORY CARDIOVASCULAR THERAPEUTIC EFFECTMartín Giménez V1, Sanz R2, Mocayar F2, Camargo A3,4, Ramírez D3,4, García S5, Yunes R5, Kassuha, DE1; Manucha, W2 1-Instituto de Investigaciones en Ciencias Químicas (UCCuyo) San Juan, Argentina. 2-Lab. Farmacol. Exp. Básica y Traslacional (IMBECU/CONICET-FCM/UNCuyo) Mendoza, Argentina. 3- Facultad de Ciencias Agrarias, Universidad Nacional de Cuyo, Mendoza, Argentina. 4-Instituto de Biología Agrícola de Mendoza (IBAM)-CONICET, Mendoza, Argentina. 5- Instituto de Investigaciones Biomédicas (INBIOMED)-IMBECU-CONICET, Universidad de Mendoza, Mendoza, Argentina. Cardiovascular remodeling (CVR) is frequently observed in hypertensive subjects. Parallel, it is known that anandamide (AEA), an endogenous cannabinoid, produces significant antihypertensive effects. However, little has been explored about its cardioprotective role because it has unfavorable physicochemical properties and, sometimes, undesirable psychoactive effects. In this context, the drug encapsulation in nanocarriers could overcome the limitations associated with the administration of AEA in free form. For this reason, the aims of the present study were to develop polymeric nanoparticles of polycaprolactone/Pluronic F127 carriers of AEA (NPs), to characterize their physicochemical properties, to determine their biocompatibility, and to evaluate their effect on the CVR and behavior of hypertensive rats treated with this nanoformulation. NPs were obtained by electrospraying technique. Subsequently, Z potential, hydrophilicity, morphology, size, thermal, and spectroscopic properties of NPs were determined. Also, the efficiency of encapsulation and loading of AEA in NPs were calculated. Biocompatibility was determined in fibroblast cultures. For the CVR studies, male rats of 250-300 g normotensive (WKY) and hypertensive (SHR), N = 7 per group, treated or not with NPs (5 mg/Kg, IP) with a weekly dose for 1 month were used. We determined, in all groups, plasmatic AEA levels, hemodynamic, structural and cardiac functional parameters, inflammatory markers of interest, and behavior associated with anxiety and exploration. From our results we can conclude that at cardiovascular level, nanoformulated AEA proved to be useful for the treatment of hypertension and its comorbidities, especially CVR, demonstrating improved physicochemical properties. Furthermore, at the central nervous system level, NPs improved animal behavior and exhibited absence of harmful effects.