Synthesis and self-assembly of curcumin-modified amphiphilic polymeric micelles with antibacterial activity

Abstract

Background The ubiquitous nature of bacterial biofilms combined with the enhanced resistance towards antimicrobials has led to the development of an increasing number of strategies for biofilm eradication. Such strategies must take into account the existence of extracellular polymeric substances, which obstruct the diffusion of antibiofilm agents and assists in the maintenance of a well-defended microbial community. Within this context, nanoparticles have been studied for their drug delivery efficacy and easily customised surface. Nevertheless, there usually is a requirement for nanocarriers to be used in association with an antimicrobial agent; the intrinsically antimicrobial nanoparticles are most often made of metals or metal oxides, which is not ideal from ecological and biomedical perspectives. Based on this, the use of polymeric micelles as nanocarriers is appealing as they can be easily prepared using biodegradable organic materials. Results In the present work, micelles comprised of poly(lactic-co-glycolic acid) and dextran are prepared and then functionalised with curcumin. The effect of the functionalisation in the micelle’s physical properties was elucidated, and the antibacterial and antibiofilm activities were assessed for the prepared polymeric nanoparticles against Pseudomonas spp. cells and biofilms. It was found that the nanoparticles have good penetration into the biofilms, which resulted in enhanced antibacterial activity of the conjugated micelles when compared to free curcumin. Furthermore, the curcumin-functionalised micelles were efficient at disrupting mature biofilms and demonstrated antibacterial activity towards biofilm-embedded cells. Conclusion Curcumin-functionalised poly(lactic-co-glycolic acid)-dextran micelles are novel nanostructures with an intrinsic antibacterial activity tested against two Pseudomonas spp. strains that have the potential to be further exploited to deliver a secondary bioactive molecule within its core. Graphic Abstract

Antibacterial and Anti-Biofilm Activities of Essential Oil Compounds against New Delhi Metallo-β-Lactamase-1-Producing Uropathogenic Klebsiella pneumoniae Strains

“…Biofilm biomass reduction was formed according to Barros et al in sterile 96-wells plates (F-bottom) [ 39 ] with a minor modification. Briefly, bacteria were grown onto Columbia agar with 5% sheep blood (Merck Life Science, Poznan, Poland) at 37 °C for 24 h. Then, one colony of each strain was transferred to 3 mL of MHB (Merck Life Science, Poznan, Poland) supplemented with 1% ( w / v ) glucose (Merck Life Science, Poznan, Poland) and re-incubated in the same abovementioned condition.…”

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“…[ 4 ] CUR can provide excellent free‐radical scavenging activity, improving the neovascularization and increasing the migratory activity of various cells, including fibroblasts, dermal myofibroblasts, and macrophages onto the wound bed. The low bioavailability and solubility, low absorption, rapid metabolism, high sensitivity (after exposure to oxygen, light, moisture, and heat), and low in vivo stability of CUR resulted in the development of various formulations with different techniques, such as self‐assembly, [ 5 ] spray drying, [ 6 ] emulsification, [ 7 ] solvent evaporation, [ 8 ] nanoprecipitation, [ 9 ] inclusion complexation, [ 10 ] liposome preparation, [ 11 ] freeze drying, [ 12 ] 3D printing, [ 13 ] electrospinning, [ 14 ] and electrospraying [ 15 ] to encapsulate CUR in different carriers for achieving better performance as compared with the free drug molecules. [ 16 ]…”

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“…The micelle product had a greater ability to penetrate biofilms resulting in superior antibacterial activity when compared to pure CUR. In addition, the functionalised carriers disrupted mature biofilms and exerted anti-bacterial activity against biofilm-embedded cells [156]. For the antibacterial and anti-biofilm assays untreated bacterial culture medium were used as the control.…”