Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

The current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro, while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis

Cardiac Regeneration using Growth Factors: Advances and Challenges

Abstract Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine

Ivermectin: an award-winning drug with expected antiviral activity against COVID-19

Ivermectin is an FDA-approved broad-spectrum antiparasitic agent with demonstrated antiviral activity against a number of DNA and RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite this promise, the antiviral activity of ivermectin has not been consistently proven in vivo. While ivermectin's activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges. Here, we discuss challenges surrounding the use of ivermectin in the context of coronavirus disease-19 (COVID-19) and how novel formulations employing micro- and nanotechnologies may address these concerns

Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro, on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-26T14:28:51Z No. of bitstreams: 1 Petersen AL Encapsulation of the HSP-90 Chaperone .....pdf: 2608327 bytes, checksum: 2db9c22cabfff8dec5cd2bfdc63df658 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-09-26T17:13:47Z (GMT) No. of bitstreams: 1 Petersen AL Encapsulation of the HSP-90 Chaperone .....pdf: 2608327 bytes, checksum: 2db9c22cabfff8dec5cd2bfdc63df658 (MD5)Made available in DSpace on 2018-09-26T17:13:47Z (GMT). No. of bitstreams: 1 Petersen AL Encapsulation of the HSP-90 Chaperone .....pdf: 2608327 bytes, checksum: 2db9c22cabfff8dec5cd2bfdc63df658 (MD5) Previous issue date: 2018Fundação de Amparo à Pesquisa do Estado da Bahia and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PV http:// www.fapesb.ba.gov.br, FAPESB.CAPES-PET 039.2013), Conselho Nacional de Pesquisa e Desenvolvimento Científico (PV http://www.cnpq.br, CNPq Universal 14/2013, Programa de Excelência em Pesquisa—PROEP/CPqGM). PV holds a grant from CNPq for productivity in research (307832/2015-5).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilFederal University of Pernambuco. Center of Biological Sciences. Graduate Program in Biological Sciences. Recife, PE, Brazil / Center of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / University of Pernambuco. Institute of Biological Sciences. Recife, PE, BrazilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, BrasilUniversity of Pernambuco. Institute of Biological Sciences. Postgraduate Program in Applied Cellular and Molecular Biology. Recife, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laborátorio de Enfermedades Infecciosas Transmitidas por Vetores. Salvador, BA, BrasilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilCenter of Strategical Technologies. Laboratory of Electron Microscopy and Microanalysis.Recife, PE, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / National Institute of Technology in Tropical Diseases-National Council for Scientific and Technological Development. Brasilia, DF, BrazilThe current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a resulting 33-fold-enhancement in compound water solubility. Stability studies revealed that 17-AAG:HPβCD-loaded liposomes were smaller than 200 nm, with 99% EE. Stability testing detected no alterations in PDI that was 0.295, pH 7.63, and zeta potential +22.6, suggesting liposome stability, and suitability for evaluating leishmanicidal activity. Treatment of infected macrophages with 0.006 nM of 17-AAG:HPβCD or 17-AAG:HPβCD-loaded liposomes resulted in almost complete amastigote clearance inside macrophages after 48 h. This reduction is similar to the one observed in infected macrophages treated with 2 μM amphotericin B. Our results showed that nanotechnology and drug delivery systems could be used to increase the antileishmanial efficacy and potency of 17-AAG in vitro, while also resulting in reduced toxicity that indicates these formulations may represent a potential therapeutic strategy against leishmaniasis

Poly(anhydride) nanoparticles containing cashew nut proteins can induce a strong Th1 and Treg immune response after oral administration

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-10T17:17:28Z No. of bitstreams: 1 Pereira M Poly(anhydride) nanoparticles containing....pdf: 1447772 bytes, checksum: 33e8c1ff21e8bdc1a7a57d3ad03ece44 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-05-10T17:27:05Z (GMT) No. of bitstreams: 1 Pereira M Poly(anhydride) nanoparticles containing....pdf: 1447772 bytes, checksum: 33e8c1ff21e8bdc1a7a57d3ad03ece44 (MD5)Made available in DSpace on 2018-05-10T17:27:05Z (GMT). No. of bitstreams: 1 Pereira M Poly(anhydride) nanoparticles containing....pdf: 1447772 bytes, checksum: 33e8c1ff21e8bdc1a7a57d3ad03ece44 (MD5) Previous issue date: 2018Brazilian Ministry of Science and Technology – MCTI (SisNANO/LARNano-UFPE, CNPq # 402282/2013-2) and FACEPE (APQ #0361-4.03/14).Federal University of Pernambuco. Immunopathology Keizo-Asami Laboratory. Recife, PE, BrazilUniversity of Pernambuco. Institute of Biological Sciences. Recife, PE, BrazilFederal University of Pernambuco. Immunopathology Keizo-Asami Laboratory. Recife, PE, BrazilUniversity of Navarra. Nanomedicines and Vaccines. Research Group. Pamplona, SpainFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita-Hospedeiro Interação e Epidemiologia. Salvador, BA, BrasilUniversity of Navarra. Nanomedicines and Vaccines. Research Group. Pamplona, SpainFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Parasita-Hospedeiro Interação e Epidemiologia. Salvador, BA, BrasilUniversity of Navarra. Nanomedicines and Vaccines. Research Group. Pamplona, SpainFederal University of Pernambuco. Immunopathology Keizo-Asami Laboratory. Recife, PE, BrazilCashew nut allergy is the second most commonly reported tree nut allergy. Traditional allergen immunotherapy presents several clinical drawbacks that can be reduced by using nanoparticles-basedallergen-delivery systems, modulating the immune response towards a protective one. In this context, the goal of this work was to assess the potential of poly(anhydride) nanoparticles (NP) for cashew nut oral immunization. Cashew nut allergens-loaded nanoparticles (CNE-NP) were prepared by solvent displacement method. After nanoparticles characterization, oral immunomodulation ability was evaluated in BALB/c mice. Our results demonstrated that CNE-NP induced a higher Th1/Th2 ratio in comparison with animals immunized with free cashew nut proteins. Indeed, a decrease in splenic Th2 cytokines (IL-4, IL-5, and IL-13), and an enhancement of pro-Th1 (IL-12 and IFN-γ) and regulatory (IL-10) cytokines was observed. Furthermore, mice orally immunized with CNE-NP presented an increased expansion of CD4+ T regulatory cells, such as CD4+Foxp3+ and CD4+LAP+, in the mesenteric lymph nodes. In conclusion, oral immunization with a single dose of poly(anhydride) nanoparticles loaded with cashew nut proteins leaded to a pro-Th1 and Treg immune response. Furthermore, their immunomodulatory properties could be introduced as a new approach for management of cashew nut allergy

Frequency of complications and the effects of pneumococcal vaccination in young children with acute respiratory tract infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-15T12:53:18Z No. of bitstreams: 1 Oliveira JR Frewquency of complications....pdf: 301134 bytes, checksum: 0b31baa07f00a1ed6270e9f924556e73 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-15T13:27:42Z (GMT) No. of bitstreams: 1 Oliveira JR Frewquency of complications....pdf: 301134 bytes, checksum: 0b31baa07f00a1ed6270e9f924556e73 (MD5)Made available in DSpace on 2016-12-15T13:27:42Z (GMT). No. of bitstreams: 1 Oliveira JR Frewquency of complications....pdf: 301134 bytes, checksum: 0b31baa07f00a1ed6270e9f924556e73 (MD5) Previous issue date: 2016FAPESB Salvador, BrazilFederal University of Bahia. School of Medicine. Postgraduate Program in Health Sciences. Salvador, BA, BrasilFederal University of Bahia. School of Medicine. Postgraduate Program in Health Sciences. Salvador, BA, BrasilSão Paulo University. School of Public Health. Department of Epidemiology. São Paulo, SP, BrasilFederal University of Bahia. School of Medicine. Postgraduate Program in Health Sciences. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Department of Pathology. Salvador, BA, BrasilFederal University of Bahia. School of Medicine. Postgraduate Program in Health Sciences. Salvador, BA, Brasil / Federal University of Bahia School of Medicine. Department of Pediatrics. Salvador, BA, BrasilFederal University of Bahia School of Medicine. Department of Pediatrics. Salvador, BA, BrasilAcute respiratory infection (ARI) is the most frequent reason for children being seen by doctors worldwide. We aimed to estimate the frequency of complications in children aged 6-23 months during ARI episode and to evaluate risk factors present on recruitment associated with complications after the universal implementation of pneumococcal vaccine (PCV10) in our region. Methods: This prospective cohort enrolled children who had shown ARI for up to 7 days and who weresubsequently followed up 14–21 days after, in Salvador, Brazil. Data on recruitment were registered.The vaccine card was personally checked. Complication was defined when hospitalization, pneumonia oracute otitis media (AOM) were informed during the follow-up visit. Pneumonia and AOM were diagnosedby a doctor. Multiple logistic regression analysis was performed.Results: Of 576 children, 422 (73%) returned and 79 (19%; 95%CI: 15–23%) had complications. The meaninterval between admission and follow-up was 23 ± 13 days. Pneumonia (n = 47; 11%), hospitalization(n = 28; 7%), and AOM (n = 17; 4%) were reported. Most of the patients presented one complication(n = 66; 84%) followed by two (n = 13; 16%). Report of fever (92% versus 79%; OR [95%CI]: 2.90 [1.18–7.14]),bird at home (24% versus 14%; OR [95%CI]: 2.13 [1.07–4.26]), ronchi (48% versus 36%; OR [95%CI]: 2.06[1.16–3.67]) or crackles (17% versus 7%; OR [95%CI]: 2.36 [1.04–5.38]) on auscultation were directly asso-ciated with complications whereas PCV10 (59% versus 75%; OR [95%CI]: 0.46 [0.26–0.82]) was inverselyassociated. Bird at home (OR [95%CI]: 5.80 [1.73–19.38]) and ronchi (OR [95%CI]: 6.39 [1.96–20.85]) wereassociated with AOM; PCV10 was inversely associated with AOM (OR [95%CI]: 0.16 [0.05–0.52]). Crackleswere associated with pneumonia (OR [95%CI]: 2.55 [1.01–6.40]).Conclusions: One fifth of the children presented complications. PCV10 was independently associatedwith lower odds of development of AOM. Bird at home and ronchi are risk factors of otitis. Crackles areassociated with pneumonia