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1.
J Biomed Mater Res A ; 109(12): 2462-2470, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34117696

RESUMO

Chitosan and alginate salts are natural biopolymers that have gained recent attention in the biomedical sectors. Their properties allow them to become potential candidates as safe, cheap, and effective vaccine adjuvants. The present study aimed to enhance the immunogenic response of a current injectable killed cholera vaccine (KCV) using chitosan and alginate salt as natural adjuvants against alum. We tested KCV adjuvanted with alum, chitosan, and sodium alginate in mice. Mice were immunized intraperitoneally with KCV adjuvanted with alum, chitosan, or alginate salt and compared with a control unadjuvanted immunized group. Humoral, cellular, and functional immune responses were evaluated in all groups. The addition of adjuvants, particularly natural adjuvants, to KCV significantly improved the immune response as demonstrated by specific antibody increase, strong proliferation effects, and high protection rate against different challenge doses of cholera strains. Our findings demonstrate that chitosan and alginate salt are superior adjuvants for boosting the KCV immune response and highlights the requirement for further vaccine development.


Assuntos
Adjuvantes de Vacinas , Alginatos/química , Materiais Biocompatíveis/química , Quitosana/química , Vacinas contra Cólera/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Compostos de Alúmen , Animais , Anticorpos Antibacterianos/análise , Imunidade Ativa/imunologia , Imunidade Humoral/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Desenvolvimento de Vacinas
2.
Sci Rep ; 11(1): 2770, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531542

RESUMO

Fungal endophytes are a major source of anti-infective agents and other medically relevant compounds. However, their classical blinded-chemical investigation is a challenging process due to their highly complex chemical makeup. Thus, utilizing cheminformatics tools such as metabolomics and computer-aided modelling is of great help deal with such complexity and select the most probable bioactive candidates. In the present study, we have explored the fungal endophytes associated with the well-known antimalarial medicinal plant Artemisia annua for their production of further antimalarial agents. Based on the preliminary antimalarial screening of these endophytes and using LC-HRMS-based metabolomics and multivariate analyses, we suggested different potentially active metabolites (compounds 1-8). Further in silico investigation using the neural-network-based prediction software PASS led to the selection of a group of quinone derivatives (compounds 1-5) as the most possible active hits. Subsequent in vitro validation revealed emodin (1) and physcion (2) to be potent antimalarial candidates with IC50 values of 0.9 and 1.9 µM, respectively. Our approach in the present investigation therefore can be applied as a preliminary evaluation step in the natural products drug discovery, which in turn can facilitate the isolation of selected metabolites notably the biologically active ones.


Assuntos
Antimaláricos , Artemisia annua/microbiologia , Endófitos/metabolismo , Metaboloma , Plasmodium falciparum/efeitos dos fármacos , Quinonas , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Endófitos/classificação , Endófitos/isolamento & purificação , Quinonas/isolamento & purificação , Quinonas/farmacologia
3.
Int J Biol Macromol ; 152: 904-912, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114177

RESUMO

The numerous recent hepatitis A outbreaks emphasize the need for vaccination; despite the effectiveness of the current ones, developments are needed to overcome its high cost plus some immune response limitations. Our study aims to evaluate the use of chitosan and alginate-coated chitosan nanoparticles as an adjuvant/carrier for the hepatitis A vaccine (HAV) against the traditional adjuvant alum. Immune responses towards (HAV-Al) with alum, (HAV-Ch) with chitosan, and (HAV-aCNP) with alginate-coated chitosan nanoparticles, were assessed in mice. HAV-aCNP significantly improved the immunogenicity by increasing the seroconversion rate (100%), the hepatitis A antibodies level, and the splenocytes proliferation. Thus, the HAV-aCNP adjuvant was superior to other classes in IFN-γ and IL-10 development. Meanwhile, the solution formula of HAV with chitosan showed comparable humoral and cellular immune responses to alum-adjuvanted suspension with a balanced Th1/Th2 immune pathway. The current study showed the potential of alginate-coated chitosan nanoparticles as an effective carrier for HAV. Consequently, this would impact the cost of HAV production positively.


Assuntos
Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Alginatos/química , Quitosana/química , Quitosana/farmacologia , Vacinas contra Hepatite A/imunologia , Nanopartículas/química , Animais , Proliferação de Células/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Soroconversão/efeitos dos fármacos , Baço/imunologia , Vacinação
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