A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.

Combining Polymer and Cyclodextrin Strategy for Drug Release of Sulfadiazine from Electrospun Fibers.

This study reports the fabrication of polymeric matrices through electrospinning using polymethyl methacrylate (PMMA) and poly(lactic-co-glycolic acid) (PLGA), biocompatible polymers commonly used in medical systems. These polymers were combined with an antibacterial drug, sulfadiazine sodium salt (SDS) or its supramolecular system formed with hydroxypropyl-ß-cyclodextrin (HPß/CD) at 1:1 molar ratio, aiming to assemble a transdermal drug delivery system. The formation of fibers was confirmed by scanning electron microscopy (SEM), and the fibers' surface properties were analyzed using contact angle and water vapor permeability techniques. Drug release tests and cell viability assays were performed to evaluate the potential toxicity of the material. SEM images demonstrated that the obtained fibers had nanoscale- and micrometer-scale diameters in PLGA and PMMA systems, respectively. The contact angle analyses indicated that, even in the presence of hydrophilic molecules (SDS and HPßCD), PMMA fibers exhibited hydrophobic characteristics, while PLGA fibers exhibited hydrophilic surface properties. These data were also confirmed by water vapor permeability analysis. The drug release profiles demonstrated a greater release of SDS in the PLGA system. Moreover, the presence of HPßCD improved the drug release in both polymeric systems and the cell viability in the PMMA SDS/HPßCD system. In terms of antibacterial activity, all membranes yielded positive outcomes; nevertheless, the PLGA SDS/HPßCD membrane exhibited the most remarkable results, with the lowest microbial load values. Additionally, the pseudo wound healing analysis demonstrated that the PLGA SDS/HPßCD fiber exhibited results similar to the control group. Consequently, these findings exemplify the substantial potential of the obtained materials for use in wound healing applications.

Electrospun Materials for Biomedical Applications.

Considered a simple and versatile technique, electrospinning has emerged as a technology for developing 3D materials for a wide range of applications [...].

Polymer-hybrid nanosystems for antiviral applications: Current advances.

The emergence of many new viruses in recent times has resulted in a significant scientific challenge for discovering drugs and vaccines that effectively treat and prevent viral diseases. Nanotechnology has opened doors to prevent the spread of several diseases, including those caused by viruses. Polymer-hybrid nanodevices are a class of nanotechnology platforms for biomedical applications that present synergistic properties among their components, with improved performance compared to conventional forms of therapy. Considering the growing interest in this emerging field and the promising technological advantages of polymer-hybrid nanodevices, this work presents the current status of these systems in the context of prevention and treatment of viral diseases. A brief description of the different types of polymer-hybrid nanodevices highlighting some peculiar characteristics such as their composition, biodistribution, delivery of antigens, and overall immune responses in systemic tissues are discussed. Finally, the work presents the future trends for new nanotechnological hybrid materials based on polymers and perspectives for clinical use.

Persistent organic pollutants: The trade-off between potential risks and sustainable remediation methods.

Persistent Organic Pollutants (POPs) have become a very serious issue for the environment because of their toxicity, resistance to conventional degradation mechanisms, and capacity to bioconcentrate, bioaccumulate and biomagnify. In this review article, the safety, regulatory, and remediation aspects of POPs including aromatic, chlorinated, pesticides, brominated, and fluorinated compounds, are discussed. Industrial and agricultural activities are identified as the main sources of these harmful chemicals, which are released to air, soil and water, impacting on social and economic development of society at a global scale. The main types of POPs are presented, illustrating their effects on wildlife and human beings, as well as the ways in which they contaminate the food chain. Some of the most promising and innovative technologies developed for the removal of POPs from water are discussed, contrasting their advantages and disadvantages with those of more conventional treatment processes. The promising methods presented in this work include bioremediation, advanced oxidation, ionizing radiation, and nanotechnology. Finally, some alternatives to define more efficient approaches to overcome the impacts that POPs cause in the hydric sources are pointed out. These alternatives include the formulation of policies, regulations and custom-made legislation for controlling the use of these pollutants.

Objective assessment of simulated non-carious cervical lesion by tridimensional digital scanning.

OBJECTIVE: To explore the use of 3D intraoral scanner/image analysis for the detection and monitoring of simulated non-carious cervical lesions (NCCLs) in vitro. MATERIALS AND METHODS: A total of 288 NCCLs of different severities and simulated using a laboratorial model associating toothbrush stiffness (soft, medium, and hard) and toothpaste abrasivity (low, medium, high, and negative control) were analyzed. Dental impressions were taken from specimens before and after 35K and 65K brushing strokes, and then scanned with a CEREC Omnicam scanner. 3D models were analyzed for volumetric tooth loss. 3D optical profilometry was considered as the gold standard. Data were analyzed using ANOVA and Fisher's PLSD tests (alpha = 0.05), and agreement between methods by using intraclass correlation coefficient. RESULTS: Toothbrushes of hard and mid stiffness caused higher tooth loss than soft when associated with the highest abrasive, at 35K and 65K strokes (p < 0.001). Variation in slurry abrasivity led to differences in tooth loss (with control < low < medium < high, p < 0.0001) after both 35K and 65K strokes, regardless of the type of toothbrush used, except at 35K, wherein control = low (p = 0.55). 35K strokes caused less tooth loss than 65K for all abrasive slurries (p < 0.0001) except controls. The intraclass correlation coefficient for agreement between the test and gold standard methods was 0.85. CONCLUSIONS: Analysis of 3D images from intraoral scanner could detect and monitor NCCL progression, although this ability was limited on incipient lesions. Overall good agreement was found between the test method and optical profilometry. CLINICAL RELEVANCE: The suggested method may be applicable to detect and monitor NCCLs clinically.

Structural and Electronic Characterization of a Photoresponsive Lanthanum(III) Complex Incorporated into Electrospun Fibers for Phosphate Ester Catalysis.

Herein, we present the light-induced synthesis and characterization of a La3+/spiropyran derivative complex (LaMC) and its application as a catalyst when incorporated into electrospun polycaprolactone (PCL) fibers. In addition to experimental methods, computational calculations were also essential to better understand the structure and electronic characteristics of LaMC. The LaMC complex was identified as a 10-coordinated structure with the La3+ ion coordinated by four oxygens from the phenolate and the carbonyl of the carboxyl acid group from both MC ligands and by six oxygens from three nitrate ligands. In addition, LaMC was capable of getting reversibly isomerized by UV or visible light cycling. All PCL fibers were successively obtained, and their morphologies, surface properties, and catalytic behavior were studied. Results showed that PCL/LaMC fibers were capable of catalyzing bis(2,4-dinitrophenyl)phosphate degradation efficiently. Complete hydrolysis was accomplished in only 1.5 days relative to the half-life time of 35 days for the uncatalyzed hydrolysis at pH 8.1 and 25 °C.

Thermodynamic compatibility between cyclodextrin supramolecular complexes and surfactant.

Supramolecular structures based on cyclodextrins have been extensively used for drug delivery systems over decades. However, combining host and guest molecules in a pharmaceutical formulation is not a trivial process, being one of the majors concern the inclusion complex compatibility with other excipients presented in the final formulation. Herein, experimental and theoretical calculations were used to investigate the competition of sodium dodecyl sulfate (SDS) with atenolol (ATE) or losartan (LOS), antihypertensive drugs widely used in the treatment of hypertension. Our findings, using nuclear magnetic resonance and isothermal titrations calorimetry experiments and molecular dynamic simulations demonstrated that LOS remain included into CD cavity after excipient (SDS) addition, which was not verified for ATE ternary system, being the drug displaced by SDS molecule.

Lead line in rodents: an old sign of lead intoxication turned into a new method for environmental surveillance.

The "lead line" was described by Henry Burton in 1840. Rodents are used as sentinels to monitor environmental pollution, but their teeth have not been used to determine lead. To determine whether lead deposits can be observed in the teeth of lead-exposed animals, since the gingival deposits known as "lead line" would likely have a correlate in the calcified tissue to which the gums are opposed during life. Male Wistar rats were exposed to lead in the drinking water (30 mg/L) since birth until 60 days-old. Molars and the incisors of each hemimandible were analyzed by scanning electron microscopy (SEM) on regular and backscattered electrons (BSE) mode. Elements were determined using electron dispersive spectroscopy (EDS). Clean cervical margins were observed on control teeth, as opposed to the findings of extensive deposits on lead-exposed animals, even in hemimandibles that had been exhumed after being buried for 90 days. BSE/EDS indicated that those deposits were an exogenous material compatible with lead sulfite. Presence of calcium, phosphorus, magnesium, carbon, lead, and oxygen is presented. Lead-exposed animals presented marked root resorption. The lead deposits characterized here for the first time show that the "lead line" seen in gums has a calcified tissue counterpart, that is detectable post-mortem even in animals exposed to a low dose of lead. This is likely a good method to detect undue lead exposure and will likely have wide application for pollution surveillance using sentinels.

Electrospun nanofibers of polyCD/PMAA polymers and their potential application as drug delivery system.

Herein, we used an electrospinning process to develop highly efficacious and hydrophobic coaxial nanofibers based on poly-cyclodextrin (polyCD) associated with poly(methacrylic acid) (PMAA) that combines polymeric and supramolecular features for modulating the release of the hydrophilic drug, propranolol hydrochloride (PROP). For this purpose, polyCD was synthesized and characterized, and its biocompatibility was assessed using fibroblast cytotoxicity tests. Moreover, the interactions between the guest PROP molecule and both polyCD and ßCD were found to be spontaneous. Subsequently, PROP was encapsulated in uniaxial and coaxial polyCD/PMAA nanofibers. A lower PROP burst effect (reduction of approximately 50%) and higher modulation were observed from the coaxial than from the uniaxial fibers. Thus, the coaxial nanofibers could potentially be a useful strategy for developing a controlled release system for hydrophilic molecules.

Treatment with Angiotensin-(1-7) reduces inflammation in carotid atherosclerotic plaques.

Angiotensin (Ang)-(1-7), acting through the receptor Mas, has atheroprotective effects; however, its role on plaque vulnerability has been poorly studied. Here, we investigated the expression of the renin-angiotensin system (RAS) components in stable and unstable human carotid plaques. In addition, we evaluated the effects of the chronic treatment with an oral formulation of Ang-(1-7) in a mouse model of shear stress-determined carotid atherosclerotic plaque. Upstream and downstream regions of internal carotid plaques were obtained from a recently published cohort of patients asymptomatic or symptomatic for ischaemic stroke. Angiotensinogen and renin genes were strongly expressed in the entire cohort, indicating an intense intraplaque modulation of the RAS. Intraplaque expression of the Mas receptor mRNA was increased in the downstream portion of asymptomatic patients as compared to corresponding region in symptomatic patients. Conversely, AT1 receptor gene expression was not modified between asymptomatic and symptomatic patients. Treatment with Ang-(1-7) in ApoE-/- mice was associated with increased intraplaque collagen content in the aortic root and low shear stress-induced carotid plaques, and a decreased MMP-9 content and neutrophil and macrophage infiltration. These beneficial effects were not observed in the oscillatory shear stress-induced plaque. In vitro incubation with Ang-(1-7) did not affect ICAM-1 expression and apoptosis on cultured endothelial cells. In conclusion, Mas receptor is up regulated in the downstream portions of human stable carotid plaques as compared to unstable lesions. Treatment with the oral formulation of Ang-(1-7) enhances a more stable phenotype in atherosclerotic plaques, depending on the local pattern of shear stress forces.

Chronic oral administration of Ang-(1-7) improves skeletal muscle, autonomic and locomotor phenotypes in muscular dystrophy.

Muscular dystrophies are a group of heterogeneous genetic disorders that cause progressive muscle weakness and wasting, dilated cardiomyopathy and early mortality. There are different types of muscular dystrophies with varying aetiologies but they all have a common hallmark of myofibre degeneration, atrophy and decreased mobility. Mutation in Sgcd (sarcoglycan-δ), a subunit of dystrophin glycoprotein complex, causes LGMD2F (limb girdle muscular dystrophy 2F). Previously, we have reported that Sgcd-deficient (Sgcd-/-) mice exhibit AngII (angiotensin II)-induced autonomic and skeletal muscle dysfunction at a young age, which contributes to onset of dilated cardiomyopathy and mortality at older ages. Two counter-regulatory RAS (renin-angiotensin system) pathways have been identified: deleterious actions of AngII acting on the AT1R (AngII type 1 receptor) compared with the protective actions of Ang-(1-7) [angiotensin-(1-7)] acting on the receptor Mas. We propose that the balance between the AngII/AT1R and Ang-(1-7)/Mas axes is disturbed in Sgcd-/- mice. Control C57BL/6J and Sgcd-/- mice were treated with Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (in drinking water) for 8-9 weeks beginning at 3 weeks of age. Ang-(1-7) treatment restored the AngII/AT1R compared with Ang-(1-7)/Mas balance, decreased oxidative stress and fibrosis in skeletal muscle, increased locomotor activity, and prevented autonomic dysfunction without lowering blood pressure in Sgcd-/- mice. Our results suggest that correcting the early autonomic dysregulation by administering Ang-(1-7) or enhancing its endogenous production may provide a novel therapeutic approach in muscular dystrophy.

An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats.

Low angiotensin-(1-7) (Ang-(1-7)) concentration is observed in some cardiovascular diseases and exercise training seems to restore its concentration in the heart. Recently, a novel formulation of an orally active Ang-(1-7) included in hydroxy-propyl-beta-cyclodextrin (HPB-CD) was developed and chronically administered in experimental models of cardiovascular diseases. The present study examined whether chronic administration of HPB-CD/Ang-(1-7) produces beneficial cardiovascular effects in spontaneously hypertensive rats (SHR), as well as to compare the results obtained with those produced by exercise training. Male SHR (15-week old) were divided in control (tap water) or treated with HPB-CD/Ang-(1-7) (corresponding to 30µgkg(-1)day(-1) of Ang-(1-7)) by gavage, concomitantly or not to exercise training (treadmill, 10 weeks). After chronic treatment, hemodynamic, morphometric and molecular analysis in the heart were performed. Chronic HPB-CD/Ang-(1-7) decreased arterial blood pressure (BP) and heart rate in SHR. The inclusion compound significantly improved left ventricular (LV) end-diastolic pressure, restored the maximum and minimum derivatives (dP/dT) and decreased cardiac hypertrophy index in SHR. Chronic treatment improved autonomic control by attenuating sympathetic modulation on heart and vessels and the SAP variability, as well as increasing parasympathetic modulation and HR variability. Overall results were similar to those obtained with exercise training. These results show that chronic treatment with the HPB-CD/Ang-(1-7) inclusion compound produced beneficial effects in SHR resembling the ones produced by exercise training. This observation reinforces the potential cardiovascular therapeutic effect of this novel peptide formulation.

Concomitant caries and calculus formation from in situ dentin caries model.

The aim of this study was to test the possibility of the concomitant formation of calculus deposits and caries from in situ dentin caries model for short time periods. Six volunteers wore palatal removal appliances with four polished dentin specimens protected from intra-oral mechanical forces for up to 14 days. Each volunteer applied a 50% sucrose solution (four times a day) on the specimens and performed a daily mouthwash with 0.05% NaF. Samples were removed after 2, 5, 9 and 14 days in situ. Demineralization was analyzed by stereomicroscopy and SEM (secondary electrons and backscattered electrons modes) and calculus was analyzed by energy dispersive spectroscopy and fluorescence spectroscopy. Seventeen samples, at least one sample from each volunteer, presented dental calculus on both carious and non-carious ones, detected in all time intervals. Ca/P ratios of dental calculus ranged from 1.1 to 1.7. Some large calculus deposits on carious surfaces were confirmed by fluorescence. In conclusion, concomitant caries and calculus formation can be found in dentin caries formed in situ. This has important repercussions on the study of surface phenomena on the interface between hard dental tissues and dental plaque.

An oral formulation of angiotensin-(1-7) reverses corpus cavernosum damages induced by hypercholesterolemia.

INTRODUCTION: The renin angiotensin system plays a crucial role in erectile function. It has been shown that elevated angiotensin-II levels contribute to the development of erectile dysfunction (ED). Oppositely, angiotensin-(1-7) (Ang-[1-7]) mediates penile erection by activation of receptor Mas. Recently, we have developed a formulation based on Ang-(1-7) inclusion in cyclodextrin (CyD) [Ang-(1-7)-CyD], which allows for the oral administration of Ang-(1-7). AIM: In the present study, we evaluated the effects of chronic treatment with Ang-(1-7)-CyD on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemic mice. METHODS: Apolipoprotein(Apo)E-/- mice fed a Western-type diet for 11 weeks received Ang-(1-7)-CyD or vehicle during the final 3 weeks. Collagen content and reactive oxygen species (ROS) production within the corpus cavernosum were evaluated by Sirius red and dihydroethidium staining, respectively. Protein expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate (NADPH) subunits (p67-phox and p22-phox), and AT1 and Mas receptors in the penis was assessed by Western blotting. Nitric oxide (NO) production was measured by Griess assay in the mice serum. Cavernosal strips were mounted in an isometric organ bath to evaluate the endothelial function. MAIN OUTCOME MEASURES: The effect of Ang-(1-7)-CyD treatment on penile fibrosis, oxidative stress, and endothelial function in hypercholesterolemia-induced ED. RESULTS: Ang-(1-7)-CyD treatment reduced collagen content in the corpus cavernosum of ApoE-/- mice. This effect was associated with an attenuation of ROS production and a diminished expression of NADPH. Furthermore, Ang-(1-7)-CyD treatment augmented the expression of nNOS and eNOS in the penis and elevated vascular NO production. Importantly, these effects were accompanied by an improvement in cavernosal endothelial function. CONCLUSION: Long-term treatment with Ang-(1-7)-CyD reduces penile fibrosis associated with attenuation of oxidative stress. Additionally, cavernosal endothelial function in hypercholesterolemic mice was markedly improved. These results suggest that Ang-(1-7)-CyD might have significant therapeutic benefits for the treatment of erectile dysfunction.

Self-assembled organic-inorganic magnetic hybrid adsorbent ferrite based on cyclodextrin nanoparticles.

Organic-inorganic magnetic hybrid materials (MHMs) combine a nonmagnetic and a magnetic component by means of electrostatic interactions or covalent bonds, and notable features can be achieved. Herein, we describe an application of a self-assembled material based on ferrite associated with ß-cyclodextrin (Fe-Ni/Zn/ßCD) at the nanoscale level. This MHM and pure ferrite (Fe-Ni/Zn) were used as an adsorbent system for Cr(3+) and Cr(2)O(7) (2-) ions in aqueous solutions. Prior to the adsorption studies, both ferrites were characterized in order to determine the particle size distribution, morphology and available binding sites on the surface of the materials. Microscopy analysis demonstrated that both ferrites present two different size domains, at the micro- and nanoscale level, with the latter being able to self-assemble into larger particles. Fe-Ni/Zn/ßCD presented smaller particles and a more homogeneous particle size distribution. Higher porosity for this MHM compared to Fe-Ni/Zn was observed by Brunauer-Emmett-Teller isotherms and positron-annihilation-lifetime spectroscopy. Based on the pKa values, potentiometric titrations demonstrated the presence of ßCD in the inorganic matrix, indicating that the lamellar structures verified by transmission electronic microscopy can be associated with ßCD assembled structures. Colloidal stability was inferred as a function of time at different pH values, indicating the sedimentation rate as a function of pH. Zeta potential measurements identified an amphoteric behavior for the Fe-Ni/Zn/ßCD, suggesting its better capability to remove ions (cations and anions) from aqueous solutions compared to that of Fe-Ni/Zn.

Insights into the multi-equilibrium, superstructure system based on ß-cyclodextrin and a highly water soluble guest.

Pentamidine isethionate (PNT) is an antiprotozoal active in many cases of leishmaniasis, despite the present limitations including high toxicity and parenteral administration. In the present work, a PNT encapsulation strategy into ß-cyclodextrin cavity at 1:1 and 2:1 (ßCD:PNT) molar ratios was used in order to improve the drug's physical and chemical properties. Combining thermodynamic and structural approaches such as isothermal titration calorimetry (ITC), electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance ((1)H NMR, and ROESY) the inclusion process and the thermodynamics parameters were identified. ITC and ESI-MS experimental data suggest the simultaneous formation of different supramolecular complexes in solution. Moreover, NMR data are in accordance with these results, suggesting a deep inclusion of PNT into the ßCD cavity, through correlations observed in 2D ROESY contour maps. The systems were also characterized by FTIR, TG/DTA and SEM. These techniques indicate the formation of inclusion complex in the solid state. In vivo PNT activity was evaluated orally in mice. The inclusion complex showed a significant reduction of parasite load compared to free PNT.

In vivo evaluation of the highly soluble oral ß-cyclodextrin-Sertraline supramolecular complexes.

The aim of the present work was to evaluate the antidepressant like-effect and plasma concentration of Sertraline (SRT) using an inclusion complex (IC) with ß-cyclodextrin (ßCD) in mice. This supramolecular system was prepared using two different molar ratios at 1:1 and 1:2 SRT:ßCD and both were characterized to assess the drug inclusion into the host cavity. Based on the X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal analysis the interaction between host and guest molecules could be suggested. This result indicates that the freeze drying process was efficient to prepare the ICs, when these are compared with the physical mixtures. By comparing the solid state results of 1:1 and 1:2 ICs no significant chemical or structural changes were identified between these systems. However, in vivo experiments indicated that the host-guest ratio was able to modify the SRT activity. Mice treated with both ICs (20 mg kg(-1), p.o.) have shown lower immobility time in the tail suspension test in comparison with mice treated with free SRT (20 mg kg(-1), p.o.). Mice spontaneous locomotor activity was not affected by any treatment. Higher SRT plasma concentration was determined after 30 min of treatment with 1:1 IC in comparison with free SRT, demonstrating the IC greater drug transport efficacy.

Beneficial effects of long-term administration of an oral formulation of Angiotensin-(1-7) in infarcted rats.

In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang)-(1-7) in hydroxypropyl ß-cyclodextrin (HPßCD), in infarcted rats. Myocardial infarction (MI) was induced by left coronary artery occlusion. HPßCD/Ang-(1-7) was administered for 60 days (76 µg/Kg/once a day/gavage) starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPßCD/Ang-(1-7) administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-ß and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1-7) and indicate HPßCD/Ang-(1-7) as a feasible formulation for long-term oral administration of this heptapeptide.