Associated Laboratory for Green Chemistry - Clean Technologies and Processes

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Publications

New potent membrane-targeting antibacterial peptides from viral capsid proteins

Publication . Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula Gomes; Andreu, David; Henriques, Sónia T.; Castanho, Miguel A. R. B.; Veiga, Ana S.

The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties.

2017Journal article

Open access

Coupling the cell-penetrating peptides transportan and transportan 10 to primaquine enhances its activity against liver-stage malaria parasites

Publication . Aguiar, Luísa; Machado, Marta; Sanches-Vaz, Margarida; Prudêncio, Miguel; Vale, Nuno; Gomes, Paula

Novel primaquine-cell penetrating peptide conjugates were synthesised and tested in vitro against liver stage Plasmodium berghei parasites. Generally, the conjugates were more active than the parent peptides and, in some cases, than the parent drug. These are unprecedented findings that may open a new route towards antimalarial drug rescuing.

2019Journal article

Restricted access

Noncovalent PEG Coating of Nanoparticle Drug Carriers Improves the Local Pharmacokinetics of Rectal Anti-HIV Microbicides

Publication . Nunes, Rute; Araújo, Francisco; Barreiros, Luísa; Bártolo, Inês; Segundo, Marcela A.; Taveira, Nuno; Sarmento, Bruno; Neves, José Das

Antiretroviral drug nanocarriers hold great promise for developing anti-human immunodeficiency virus (HIV) rectal microbicides. However, challenges remain, namely, concerning which properties are more suited for enhancing colorectal distribution and retention of microbicide compounds. In this work, we developed and assessed the in vitro and in vivo performance of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) as carriers for the model drug efavirenz (EFV). We particularly focused on the effect of noncovalent poly(ethylene glycol) coating of PLGA NPs (PEG–PLGA NPs) conferring a mucus-diffusive behavior on the pharmacokinetics (PK) of EFV following rectal administration to mice. Drug-loaded PLGA NPs and PEG–PLGA NPs (200–225 nm) were obtained by nanoprecipitation. Both types of systems were able to retain native antiretroviral activity of EFV in vitro, while featuring lower cytotoxicity against different epithelial cell lines and HIV target cells. Also, PLGA NPs and PEG–PLGA NPs were readily taken up by colorectal cell lines and mildly reduced EFV permeation while increasing membrane retention in Caco-2 and Caco-2/HT29-MTX cell monolayer models. When administered intrarectally to CD-1 mice in phosphate-buffered saline (pH 7.4), EFV-loaded PEG–PLGA NPs consistently provided higher drug levels in colorectal tissues and lavages, as compared to free EFV or drug-loaded PLGA NPs. Mean values for the area-under-the-curve between 15 min and 12 h following administration were particularly higher for PEG–PLGA NPs in distal and middle colorectal tissues, with relative bioavailability values of 3.7 and 29, respectively, as compared to free EFV (2.2 and 6.0 over PLGA NPs, respectively). Systemic exposure to EFV was reduced for all treatments. NPs were further shown safe after once-daily administration for 14 days, as assessed by histological analysis of colorectal tissues and chemokine/cytokine assay of rectal lavages. Overall, PEG–PLGA NPs demonstrated to be safe carriers for rectal microbicide drug delivery and able to provide enhanced local PK that could be valuable in preventing rectal HIV transmission.

2018Journal article

Restricted access

Antibacterial application of natural and carboxymethylated cashew gum-based silver nanoparticles produced by microwave-assisted synthesis

Publication . Araruna, Felipe Bastos; de Oliveira, Taiane Maria; Quelemes, Patrick Veras; de Araújo Nobre, Alyne Rodrigues; Plácido, Alexandra; Vasconcelos, Andreanne Gomes; de Paula, Regina Célia Monteiro; Mafud, Ana Carolina; de Almeida, Miguel Peixoto; Delerue-Matos, Cristina; Mascarenhas, Yvonne Primerano; Eaton, Peter; de Souza de Almeida Leite, José Roberto; da Silva, Durcilene Alves

This study presents a green synthesis route to silver nanoparticles (AgNPs) stabilized with cashew gum (CG) or carboxymethylated cashew gum (CCG) using microwave-assisted synthesis and evaluates their antibacterial activity. The antimicrobial activity was measured by determining the minimum inhibitory concentration (MIC) with Staphylococcus aureus and Escherichia coli. In both cases of the presence of CG and CCG, it was found that higher pH lead to more efficient conversion of silver nitrate to AgNPs with well dispersed, spherical and stable particles as well as low crystallinity. CCG-capped AgNPs were slightly smaller (137.0 and 96.3 nm) than those coated with non-modified gum (144.7 and 100.9 nm). The samples presented promising antibacterial activity, especially on Gram-negative bacteria, resulting in significant membrane damage on treated bacteria in comparison to the untreated control, observed by atomic force microscopy. Thus, a quick and efficient synthesis route was applied to produce CGAgNPs and CCGAgNPs with antimicrobial potential.

2020Journal article

Restricted access