Nanotechnology-based drug delivery systems for control of microbial biofilms: a review

Matheus Aparecido Dos Santos Ramos,1 Patrícia Bento Da Silva,2 Larissa Spósito,1 Luciani Gaspar De Toledo,1 Bruna Vidal Bonifácio,1 Camila Fernanda Rodero,2 Karen Cristina Dos Santos,2 Marlus Chorilli,2 Taís Maria Bauab1 1São Paulo State University (UNESP), School of Pharmaceutical Sciences, Campus Araraquara, Department of Biological Sciences, Araraquara, SP, Brazil; 2São Paulo State University (UNESP), School of Pharmaceutical Sciences, Campus Araraquara, Department of Drugs and Medicines. Araraquara, SP, Brazil Abstract: Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms. Keywords: nanotechnology systems, microbial biofilms, anti-biofilm activit

Marine green macroalgae: a source of natural compounds with mineralogenic and antioxidant activities

Marine macroalgae represent a valuable natural resource for bioactive phytochemicals with promising applications in therapeutics, although they remain largely under-exploited. In this work, the potential of two marine green macroalgae (Cladophora rupestris and Codium fragile) as a source of bioactive phenolic compounds was explored, and antioxidant, mineralogenic, and osteogenic activities were evaluated. For each species, a crude hydroalcoholic extract (CE) was prepared by solid/liquid extraction and fractionated by liquid/liquid purification into an ethyl acetate fraction (EAF) enriched in phenolic compounds and an aqueous fraction (AF). Antioxidant activity, assessed through radical scavenging activity and reducing power assay, was increased in EAF fraction of both species and closely related to the phenolic content in each fraction. Mineralogenic activity, assessed through extracellular matrix mineralization of a fish bone-derived cell line, was induced by EAF fractions (up to 600 % for C. rupestris EAF). Quantitative analysis of operculum formation in zebrafish larvae stained with alizarin red S further confirmed the osteogenic potential of EAF fractions in vivo, with an increase of more than 1.5-fold for both C. fragile and C. rupestris fractions, similar to vitamin D (control). Our results demonstrated a positive correlation between phenolic fractions and biological activity, suggesting that phenolic compounds extracted from marine green macroalgae may represent promising molecules toward therapeutic applications in the field of bone biology.European Regional Development Fund (ERDF)-Atlantic Area Programme through MARMED project [2011-1/164]European Era-Net, Seas-Era program through the project INVASIVES [ANR-12-SEAS-0002-01]Portuguese Foundation for Science and Technology (FCT) [UID/Multi/04326/2013