Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity

Abstract

Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs) on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC) assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio), the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.

Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole

“…However, the amount of POS released from formulation composed of only OLG (F4) was 100% just after 3 h of the study. The drug release rate is an important factor influencing the efficacy of antifungal compounds as it affects inhibition of the microbes' growth and prevents drug resistance [31]. Surprisingly, the amount of POS released from formulations F2 and F3 after 3 h was similar, indicating that it was not ALG and OLG concentration-dependent.…”

Dos distúrbios psiquiátricos à antibioticoterapia: reposicionamento da clorpromazina como agente antibacteriano

“…A adaptação necessária que garante o estabelecimento do processo infeccioso é dependente dos fatores de virulência [103,104]. A principal característica biológica das bactérias que afeta a saúde humana reside na capacidade desses microrganismos em formar biofilmes [58,105]. Essas estruturas são caracterizadas por um conjunto de células aderentes com propriedades que as distinguem daqueles livres (planctônicas), como a grande resistência a agentes antimicrobianos químicos e físicos [105].…”

“…Assim sendo, sugere-se que a concentração necessária para induzir o efeito antibacteriano da CPZ contra patógenos intracelulares é associada a uma baixa toxicidade clínica. [20,58], Klebsiella pneumoniae (CIM 64-128 µg/mL) [58] e Salmonella enterica serovar Typhimurium (CIM 110-512 µg/mL) [21,63], e contra os bastonetes Gram-negativos não-fermentadores Acinetobacter antiratus (CIM 60 µg/mL) [20] e Acinetobacter baumannii (CIM 64 µg/mL) [58]. Em adição a atividade bacteriostática contra A. baumannii, a CPZ (128 µg/mL) possui a habilidade de reduzir em 3 log a densidade celular desse microrganismo após 3 h de incubação, demostrando assim o potencial bactericida desse fármaco também contra espécies de Gram-negativas [58].…”

“…[20,58], Klebsiella pneumoniae (CIM 64-128 µg/mL) [58] e Salmonella enterica serovar Typhimurium (CIM 110-512 µg/mL) [21,63], e contra os bastonetes Gram-negativos não-fermentadores Acinetobacter antiratus (CIM 60 µg/mL) [20] e Acinetobacter baumannii (CIM 64 µg/mL) [58]. Em adição a atividade bacteriostática contra A. baumannii, a CPZ (128 µg/mL) possui a habilidade de reduzir em 3 log a densidade celular desse microrganismo após 3 h de incubação, demostrando assim o potencial bactericida desse fármaco também contra espécies de Gram-negativas [58]. O efeito antibacteriano também foi mensurado contra Proteus vulgaris [20] e Pseudomonas aeruginosa [20,58,61], mas em ambos os casos a CPZ foi inativa (CIM >500 µg/mL).…”

“…Em adição a atividade bacteriostática contra A. baumannii, a CPZ (128 µg/mL) possui a habilidade de reduzir em 3 log a densidade celular desse microrganismo após 3 h de incubação, demostrando assim o potencial bactericida desse fármaco também contra espécies de Gram-negativas [58]. O efeito antibacteriano também foi mensurado contra Proteus vulgaris [20] e Pseudomonas aeruginosa [20,58,61], mas em ambos os casos a CPZ foi inativa (CIM >500 µg/mL).…”