Development and assessment of an inedite nanoformulation of anandamide with a promissory cardiovascular therapeutic effect

RAÚL SANZ; DANIELA RAMIREZ; DIEGO KASSUHA; VIRNA MARTÍN GIMENÉZ; ALEJANDRA CAMARGO; ROBERTO YUNES; FERES MOCAYAR; GARCÍA SEBASTIÁN; WALTER MANUCHA

Mendoza

Simposio; XIV Jornadas de Investigación FCM y del II Simposio de Medicina Traslacional.; 2019

Introduction: 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.Objectives: 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.Methods: NPs were obtained by electrospinning 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. Results: We obtained particles with optimal physicochemical and biocompatibility properties. In SHR, treatment with NPs reversed all hemodynamic, structural and cardiac functional parameters, as well as altered inflammatory markers (P