PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers.

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation.

Potencial antimicrobiano dos antissépticos de uso popular anapyon®, água rabelo® e malvatricin® sobre microrganismos do meio ambiente oral / Antimicrobial Potential of the Popular Antiseptics Anapyon®, Água Rabelo® and Malvatricin® against Oral Microorganisms

Objetivo: Verificar, ?in vitro?, o potencial antimicrobiano do Anapyon®, da Água Rabelo® e do Malvatricin® sobre microrganismos presentes na cavidade oral.Método: Para realização do experimento, utilizou-se o protocolo sequenciado durante quatro dias que avaliou, através da medida da densidade óptica, o potencial antimicrobiano dos fármacos nos microrganismos (Staphylococcus aureus, Candida tropicalis, Candida parapsilosis e Candida albicans), em suas formas planctônicas, apenas o Malvatricin® foi avaliado sobre as formas de biofilme por ser o único fármaco que apresentou resultados satisfatórios sobre as formas planctônicas. O estudo adotou como controle negativo a água destilada e controle positivo a Clorexidina®. Os resultados obtidos foram submetidos a uma análise estatística com os testes de Kruskal-Wallis e Mann-Whitney. Resultados: Observou-se, através da medida da densidade óptica, que apenas o Malvatricin® apresentou bons resultados na forma planctônica, sendo estes semelhantes ao controle positivo (clorexidina), considerado padrão nos ensaios antimicrobianos em Odontologia. Os resultados do Malvatricin® foram estatisticamente melhores quando comparados aos demais fármacos (Anapyon®, Água Rabelo®) e ao controle negativo. Este resultado foi semelhante para todos os microrganismos estudados: Staphylococcus aureus (p=0,002), Candida tropicalis (p=0,002), Candida parapsilosis (p=0,001) e Candida albicans (p<0,001). Desta forma, apenas o Mavatricin® foi testado para o microrganismo arranjado em biofilme. Observou-se, então, que para a C.albicans e para o S. aureus, houve diferença significativa entre clorexidina e Malvatricin® (p<0,05), com melhores resultados para o clorexidina. Para C. tropicalis, o Malvatricin® diferiu significativamente (p<0,05) da água destilada. Em relação a C.parapsilosis, nenhuma diferença foi observada em relação ao controle negativo (p=0,468). Conclusão: Apesar de alguns fármacos alternativos serem tidos como antimicrobianos, tais propriedades sobre células planctônicas e, principalmente, sobre biofilme foram observadas apenas para o Malvatricin®.

Objective: To evaluate in vitro the antimicrobial potential of Anapyon®, Água Rabelo and Malvatricin® against oral microorganisms.Method: The experiment used a four-day sequential protocol that evaluated by optical density measurements the antimicrobial potential of these products against Staphylococcus aureus, Candida tropicalis, Candida parapsilosis and Candida albicans in their planktonic forms. Only Malvatricin® was also evaluated against microbial biofilms because it was the only one to produce satisfactory results against the planktonic forms. Distilled water was used as negative control and Chlorhexidine® as positive control. The data were analyzed statistically by the Kruskal-Wallis and Mann-Whitney tests. Results: According to the optical density readings, only Malvatricin® was effective against the planktonic microorganisms and its results were similar to those of the positive control (Chlorhexidine), which is the gold standard antimicrobial agent in dental research. Malvatricin® presented significantly higher efficacy than the other antiseptics (Anapyon® and Água Rabelo®) and the negative control, and this result was similar for all tested microorganisms: S. aureus (p=0.002), C tropicalis (p=0.002), C. parapsilosis (p=0.001) and C. albicans (p<0.001). For this reason, only Malvatricin® was evaluated against the microorganisms arranged as biofilms. Chlorhexidine presented significantly better results (p<0.05) than Malvatricin® against C. albicans and S. aureus. When tested against C. tropicalis, Malvatricin® differed significantly (p<0.05) from distilled water, while against C. parapsilosis no significant difference (p=0.468) was observed in comparison with the negative control. Conclusion: Although some pharmaceutical products being considered anti-microbial, such properties against planktonic cells and especially the biofilms were observed only for Malvatricin®.

Ultrastructural changes in bacterial membranes induced by nano-assemblies ß-cyclodextrin chlorhexidine: SEM, AFM, and TEM evaluation.

Chemical hosts bind their guests by the same physical mechanisms as biomolecules and often display similarly subtle structure activity relationships. The cyclodextrins have found increasing application as inert, nontoxic carriers of active compounds in drug formulations. The present study was conducted to prepare inclusion complexes of chlorhexidine:ß-cyclodextrin (Cx:ß-cd), and evaluate their interactions with bacterial membrane through: scanning electron microscopy (SEM) and transmission electron microscopy (TEM); and measuring morphology alterations, roughness values, and cell weights by atomic force microscopy (AFM). It was found that the antimicrobial activity was significantly enhanced by cyclodextrin encapsulation. SEM analysis images demonstrated recognizable cell membrane structural changes and ultrastructural membrane swelling. By TEM, cellular alterations such as vacuolization, cellular leakage, and membrane defects were observed; these effects were enhanced at 1:3 and 1:4 Cx:ß-cd. In addition, AFM analysis at these ratios showed substantially more membrane disruption and large aggregates mixing with microorganism remains. In conclusion, nanoaggregates formed by cyclodextrin inclusion compounds create cluster-like structures with the cell membrane, possibly due to a hydrogen rich bonding interaction system with increasing surface roughness and possibly increasing the electrostatic interaction between cationic chlorhexidine with the lipopolysaccharides of Gram negative bacteria.

Avaliação química do parâmetro físico-químico de soluções de digluconato de clorexidina 02 por cento disponíveis no mercado / Chemical analysis of physical chemical parameter of commercially available 02 by cent chlorhexidine digluconate solutions

Foi realizada uma análise química de 11 amostras de soluções de digluconato de clorexidina a 2,0 por cento disponíveis em casas de materiais odontológicos e farmácias de manipulação de Porto Alegre - RS e Tubarão - SC, a fim de averiguar a especificação do produto. Para tanto, veririficou-se o teor de sal do digluconato de clorexidina nas amostras por meio de cromatografia liquida de lata eficiência (CLAE/HPLC). A metodologia utilizada no presente estudo foi baseada na empregada pelo Depertament of Health, Social Services and Public from Northen Ireland (1993). Os resultados encontrados evidenciaram que apenas duas das 11 amostras analisadas estavam fora dos limites de especificação, comprovando ser o digluconato de clorexidina uma substância com adequado controle de qualidade.

Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis.

In an approach to discover new inhibitors of trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease, a virtual high-throughput screening was performed. Two structurally new types of inhibitors emerged, the antimicrobial chlorhexidine {1,1'-hexamethylenebis[5-(4-chlorophenyl)biguanide]}, a linear competitive inhibitor (K(i) = 2 +/- 1 microM), and a piperidine derivative acting as mixed inhibitor (K(i) = 6.2 +/- 2 microM and K(i)' = 8.5 +/- 2 microM). Neither compound interferes with human glutathione reductase. Based on chlorhexidine, different series of compounds were synthesized and studied as inhibitors of T. cruzi trypanothione reductase. Most efficient derivatives were three bis(amidines) showing mixed type inhibition with K(i,slope) and K(i,int) values of 2-5 microM and 16-47 microM, respectively. Although these compounds did not exert an improved inhibitory potency compared to chlorhexidine, the change from competitive to mixed-type inhibition is advantageous, since substrate accumulation does not overcome inhibition. Remarkably, all three derivatives carried two copies of an identical 2-methoxy-4-methyl-1-(phenylmethoxy)benzene substituent.