Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles

none10The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.openAdriana Trapani, Lorenzo Guerra, Filomena Corbo, Stefano Castellani, Enrico Sanna, Loredana Capobianco, Anna Grazia Monteduro, Daniela Erminia Manno, Delia Mandracchia, Sante Di Gioia and Massimo ConeseTrapani, Adriana; Guerra, Lorenzo; Corbo, Filomena; Castellani, Stefano; Sanna, Enrico; Capobianco, Loredana; Monteduro, ANNA GRAZIA; Manno, Daniela Erminia; Mandracchia, Delia; Di Gioia and Massimo Conese, Sant

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Novel Nanoparticles Based on N,O-Carboxymethyl Chitosan-Dopamine Amide Conjugate for Nose-to-Brain Delivery

A widely investigated approach to bypass the blood brain barrier is represented by the intranasal delivery of therapeutic agents exploiting the olfactory or trigeminal connections nose-brain. As for Parkinson’s disease (PD), characterized by dopaminergic midbrain neurons degeneration, currently there is no disease modifying therapy. Although several bio-nanomaterials have been evaluated for encapsulation of neurotransmitter dopamine (DA) or dopaminergic drugs in order to restore the DA content in parkinsonian patients, the premature leakage of the therapeutic agent limits this approach. To tackle this drawback, we undertook a study where the active was linked to the polymeric backbone by a covalent bond. Thus, novel nanoparticles (NPs) based on N,O-Carboxymethylchitosan-DA amide conjugate (N,O-CMCS-DA) were prepared by the nanoprecipitation method and characterized from a technological view point, cytotoxicity and uptake by Olfactory Ensheating Cells (OECs). Thermogravimetric analysis showed high chemical stability of N,O-CMCS-DA NPs and X-ray photoelectron spectroscopy evidenced the presence of amide linkages on the NPs surface. MTT test indicated their cytocompatibility with OECs, while cytofluorimetry and fluorescent microscopy revealed the internalization of labelled N,O-CMCS-DA NPs by OECs, that was increased by the presence of mucin. Altogether, these findings seem promising for further development of N,O-CMCS-DA NPs for nose-to-brain delivery application in PD

Novel Nanoparticles Based on N,O-Carboxymethyl Chitosan-Dopamine Amide Conjugate for Nose-to-Brain Delivery

A widely investigated approach to bypass the blood brain barrier is represented by the intranasal delivery of therapeutic agents exploiting the olfactory or trigeminal connections nosebrain. As for Parkinson’s disease (PD), characterized by dopaminergic midbrain neurons degeneration, currently there is no disease modifying therapy. Although several bio-nanomaterials have been evaluated for encapsulation of neurotransmitter dopamine (DA) or dopaminergic drugs in order to restore the DA content in parkinsonian patients, the premature leakage of the therapeutic agent limits this approach. To tackle this drawback, we undertook a study where the active was linked to the polymeric backbone by a covalent bond. Thus, novel nanoparticles (NPs) based on N,O-Carboxymethylchitosan-DA amide conjugate (N,O-CMCS-DA) were prepared by the nanoprecipitation method and characterized from a technological view point, cytotoxicity and uptake by Olfactory Ensheating Cells (OECs). Thermogravimetric analysis showed high chemical stability of N,O-CMCS-DA NPs and X-ray photoelectron spectroscopy evidenced the presence of amide linkages on the NPs surface. MTT test indicated their cytocompatibility with OECs, while cytofluorimetry and fluorescent microscopy revealed the internalization of labelled N,O-CMCS-DA NPs by OECs, that was increased by the presence of mucin. Altogether, these findings seem promising for further development of N,O-CMCS-DA NPs for nose-to-brain delivery application in PD

Cyto/Biocompatibility of Dopamine Combined with the Anti-oxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles

Abstract: Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoad-hesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuro-blastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting can-didates for non-invasive nose-to-brain delivery

Retinal thinning in progressive supranuclear palsy: differences with healthy controls and correlation with clinical variables

Background: Available evidence reports conflicting data on retinal thickness in progressive supranuclear palsy (PSP). In studies including healthy controls, PSP showed either the thinning of the retinal nerve fiber layer, macular ganglion cell, inner nuclear, or outer retina layer. Objectives: The goals of the present study were to describe retinal layer thickness in a large cohort of PSP compared to healthy controls and in PSP phenotypes using spectral-domain optical coherence tomography (SD-OCT). The additional objective was to verify the relationship between retinal layers thickness and clinical variables in PSP. Methods: Using a cross-sectional design, we examined retinal structure in 27 PSP patients and 27 controls using standard SD-OCT. Motor and cognitive impairment in PSP was rated with the PSP rating scale and the Montreal Cognitive Assessment battery (MoCA), respectively. Eyes with poor image quality or confounding diseases were excluded. SD-OCT measures of PSP and controls were compared with parametric testing, and correlations between retinal layer thicknesses and disease severity were evaluated. Results: PSP showed significant thinning of the inner retinal layer (IRL), ganglion cell layer (GCL), inner plexiform layer (IPL), and the outer plexiform layer (OPL) compared to healthy controls. PSP phenotypes showed similar retinal layer thicknesses. Retinal layer thickness correlated with MoCA visuospatial subscore (p < 0.001). Conclusions: We demonstrated PSP patients disclosed thinner IRL, GCL, IPL, and OPL compared to healthy controls. Furthermore, we found a significant correlation between visuospatial abilities and retinal layers suggesting the existence of a mutual relationship between posterior cognitive function and retinal structure

Mucopenetration study of solid lipid nanoparticles containing magneto sensitive iron oxide

n most chronic respiratory diseases, excessive viscous airway secretions oppose a formidable permeation barrier to drug delivery systems (DDSs), with a limit to their therapeutic efficacy for the targeting epithelium. Since mucopenetration of DDSs with slippery technology (i.e. PEGylation) has encountered a reduction in the presence of sticky and complex airway secretions, our aim was to evaluate the relevance of magnetic PEGylated Solid Lipid Nanoparticles (mSLNs) for pulling them through chronic obstructive pulmonary disease (COPD) airway secre tions. Thus, COPD sputum from outpatient clinic, respiratory secretions aspirated from high (HI) and low (LO) airways of COPD patients in acute respiratory insufficiency, and porcine gastric mucus (PGM) were investigated for their permeability to mSLN particles under a magnetic field. Rheological tests and mSLN adhesion to airway epithelial cells (AECs) were also investigated. The results of mucopenetration show that mSLNs are permeable both in COPD sputum and in PGM, while HI and LO secretions are always impervious. Parallel rheological results show a different elastic property, which can be associated with different mucus mesostructures. Finally, adhesion tests confirm the role of the magnetic field in improving the interaction of SLNs with AECs. Overall, our results reveal that mesostructure is of paramount importance in determining the mucopenetration of magnetic SLNs

Low prevalence of cardiac abnormalities in competitive athletes at return-to-play after COVID-19

Objective: to evaluate the prevalence of cardiac involvement after COVID-19 in competitive athletes at return-to-play (RTP) evaluation, following the recommended Italian protocol including cardiopulmonary exercise test (CPET) and 24-Hour Holter monitoring. Design and methods: this is a single centre observational, cross-sectional study. Since October 2020, all competitive athletes (age ≥ 14 years) evaluated in our Institute after COVID-19, prior RTP were enrolled. The protocol dictated by the Italian governing bodies included: 12‑lead ECG, blood test, CPET, 24-h ECG monitoring, spirometry. Cardiovascular Magnetic Resonance (CMR) was performed based on clinical indication. Results: 219 consecutive athletes were examined (59% male), age 23 years (IQR 19-27), 21% asymptomatic, 77% mildly symptomatic, 2% with previous pneumonia. The evaluation was performed after a median of 10 (6-17) days from negative SARS-CoV-2 swab. All athletes showed a good exercise capacity at CPET without cardiovascular and respiratory limitations. Uncommon premature ventricular contractions (PVCs) were found in 9.5% (n = 21) at CPET/Holter ECG monitoring. Two athletes (0.9%) were diagnosed with acute myocarditis (by CMR) and another one with new pericardial effusion. All the three athletes were temporally restricted from sport participation. Conclusions: Myocarditis in competitive athletes screened after COVID-19 resolution was detected in a low minority of the cases (0.9%). However, a non-negligible prevalence of uncommon PVCs (9%) was observed, either at CPET and/or Holter ECG monitoring, including all athletes with COVID-19 related cardiovascular abnormalities