Synthesis, physicochemical characterisation and biological activity of anandamide/ɛ-polycaprolactone nanoparticles obtained by electrospraying.

Drug encapsulation in nanocarriers such as polymeric nanoparticles (Nps) may help to overcome the limitations associated with cannabinoids. In this study, the authors' work aimed to highlight the use of electrospraying techniques for the development of carrier Nps of anandamide (AEA), an endocannabinoid with attractive pharmacological effects but underestimated due to its unfavourable physicochemical and pharmacokinetic properties added to its undesirable effects at the level of the central nervous system. The authors characterised physicochemically and evaluated in vitro biological activity of anandamide/ɛ-polycaprolactone nanoparticles (Nps-AEA/PCL) obtained by electrospraying in epithelial cells of the human proximal tubule (HK2), to prove the utility of this method and to validate the biological effect of Nps-AEA/PCL. They obtained particles from 100 to 900 nm of diameter with a predominance of 200-400 nm. Their zeta potential was -20 ± 1.86 mV. They demonstrated the stable encapsulation of AEA in Nps-AEA/PCL, as well as its dose-dependent capacity to induce the expression of iNOS and NO levels and to decrease the Na+/K+ ATPase activity in HK2 cells. Obtaining Nps-AEA/PCL by electrospraying would represent a promising methodology for a novel AEA pharmaceutical formulation development with optimal physicochemical properties, physical stability and biological activity on HK2 cells.

Preparation and characterization of bosentan monohydrate/ε-polycaprolactone nanoparticles obtained by electrospraying.

The electrospraying technique provides nano and microparticles that can be used as drug delivery systems. The aims of this study were, firstly, to optimize the influent parameters of electrospraying for the manufacture of a Bosentan (BOS) nanoparticulate platform, and secondly, to evaluate its physicochemical properties and in vitro biopharmaceutical behavior. Particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier transformed Infrared spectroscopy (FTIR). Drug loading, encapsulation efficiency and kinetic dissolution were determined. Additionally, Bosentan release assays at 24 and 72 h were performed in vitro to evaluate biopharmaceutical properties of nano-scaffolds by diffusion technique through dialysis bag. The nanostructures had heterogeneous sizes predominantly smaller than 550 nm and they were semicrystalline according to PXRD, indicating a partial amorphization of BOS during the encapsulation in the polymer matrix. FT-IR and DSC showed an absence of chemical interactions between BOS and ε-Polycaprolactone (PCL), suggesting that both components behaved as a physical mixture in these particles. The drug loading was 25.98%, and the encapsulation efficiency was 58.51%. Additionally, the release assays showed an extended and controlled release of BOS, in comparison to non-encapsulated BOS. These data also showed to fit with the Cubic Root kinetic dissolution. As a conclusion, we demonstrate that the use of electrospraying for the manufacture of BOS (or similar drugs) controlled release nanoplatforms would represent an interesting contribution in the development of new therapeutic alternatives for the treatment of pathologies such as pulmonary hypertension and other related diseases. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2748, 2019.

Anandamide-nanoformulation obtained by electrospraying for cardiovascular therapy.

Anandamide (AEA), an endogenous cannabinoid, has a relevant antihypertensive effect. However, its cardioprotective role has been barely explored due to unfavorable physico-chemical properties and, sometimes, undesirable psychoactive effects. In this context, drug encapsulation in nanocarriers could overcome the limitations associated with the administration of AEA in free form. The aim of the present study was to encapsulate AEA in poly-ε-caprolactone/Pluronic® F127 nanoparticles (AEA/PCL/PF127 NPs) by means of electrospraying, to characterize their physico-chemical properties and cytocompatibility and to evaluate their effect in an in vivo model of cardiovascular remodeling caused by hypertension. AEA/PCL/PF127 NPs were characterized in terms of morphology, size, polydispersity, Z-potential, hydrophilicity, thermal and spectroscopic properties. Also, the encapsulation and loading efficiencies and in vitro release of AEA were analyzed. AEA/PCL/PF127 NPs (700-1000 nm) showed adequate cytocompatibility. For the cardiovascular remodeling studies, normotensive (WKY) and hypertensive (SHR) male rats were treated or not with AEA/PCL/PF127 NPs (5 mg/Kg, intraperitoneal injection) weekly for 1 month. Inflammatory markers and hemodynamic, structural and cardiac functional parameters were monitored. In SHR, the treatment with AEA/PCL/PF127 NPs reversed all altered cardiovascular markers and parameters (p < 0.05). Overall, nanoformulated AEA obtained by electrospraying proved to be effective for the treatment of hypertension and its comorbidities, especially cardiovascular remodeling.