Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.

Synergistic antimicrobial photodynamic therapy using gated mesoporous silica nanoparticles containing curcumin and polymyxin B.

Photodynamic Therapy is a therapy based on combining a non-toxic compound, known as photosensitizer (PS), and irradiation with light of the appropriate wavelength to excite the PS molecule. The photon absorption by the PS leads to reactive oxygen species generation and a subsequent oxidative burst that causes cell damage and death. In this work, we report an antimicrobial nanodevice that uses the activity of curcumin (Cur) as a PS for antimicrobial Photodynamic Therapy (aPDT), based on mesoporous silica nanoparticles in which the action of the classical antibiotic PMB is synergistically combined with the aPDT properties of curcumin to combat bacteria. The synergistic effect of the designed gated device in combination with irradiation with blue LED light (470 nm) is evaluated against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. The results show that the nanodevice exhibits a noteworthy antibacterial activity against these microorganisms, a much more significant effect than free Cur and PMB at equivalent concentrations. Thus, 0.1 µg/mL of MSNs-Cur-PMB eliminates a bacterial concentration of about 105 CFU/mL of E. coli, while 1 µg/mL of MSNs-Cur-PMB is required for P. aeruginosa and S. epidermidis. In addition, antibiofilm activity against the selected bacteria was also tested. We found that 0.1 mg/mL of MSNs-Cur-PMB inhibited 99 % biofilm formation for E. coli, and 1 mg/mL of MSNs-Cur-PMB achieved 90 % and 100 % inhibition of biofilm formation for S. epidermidis and P. aeruginosa, respectively.

Exploring the Synergy between Nano-Formulated Linezolid and Polymyxin B as a Gram-Negative Effective Antibiotic Delivery System Based on Mesoporous Silica Nanoparticles.

Antimicrobial resistance is a current silent pandemic that needs new types of antimicrobial agents different from the classic antibiotics that are known to lose efficiency over time. Encapsulation of antibiotics inside nano-delivery systems could be a promising, effective strategy that is able to delay the capability of pathogens to develop resistance mechanisms against antimicrobials. These systems can be adapted to deliver already discovered antibiotics to specific infection sites in a more successful way. Herein, mesoporous silica nanomaterials are used for an efficient delivery of a linezolid gram-positive antibiotic that acts synergistically with gram-negative antimicrobial polymyxin B. For this purpose, linezolid is encapsulated in the pores of the mesoporous silica, whose outer surface is coated with a polymyxin B membrane disruptor. The nanomaterial showed a good controlled-release performance in the presence of lipopolysaccharide, found in bacteria cell membranes, and the complete bacteria E. coli DH5α. The performed studies demonstrate that when the novel formulation is near bacteria, polymyxin B interacts with the cell membrane, thereby promoting its permeation. After this step, linezolid can easily penetrate the bacteria and act with efficacy to kill the microorganism. The nano-delivery system presents a highly increased antimicrobial efficacy against gram-negative bacteria, where the use of free linezolid is not effective, with a fractional inhibitory concentration index of 0.0063 for E. coli. Moreover, enhanced toxicity against gram-positive bacteria was confirmed thanks to the combination of both antibiotics in the same nanoparticles. Although this new nanomaterial should be further studied to reach clinical practice, the obtained results pave the way to the development of new nanoformulations which could help in the fight against bacterial infections.

Gated Organonanoclays for Large Biomolecules: Controlled Release Triggered by Surfactant Stimulus.

The low toxicity and high adsorption capacities of clay minerals make them attractive for controlled delivery applications. However, the number of controlled-release studies in the literature using clay minerals is still scarce. In this work, three different clays from the smectite group (Kunipia F, montmorillonite; Sumecton SA, saponite; and Sumecton SWN, hectorite) were successfully loaded with rhodamine B dye and functionalized with oleic acid as a gatekeeper to produce organonanoclays for active and controlled payload-release. Moreover, hematin and cyanocobalamin have also been encapsulated in hectorite gated clay. These organonanoclays were able to confine the entrapped cargos in an aqueous environment, and effectively release them in the presence of surfactants (as bile salts). A controlled delivery of 49 ± 6 µg hematin/mg solid and 32.7 ± 1.5 µg cyanocobalamin/mg solid was reached. The cargo release profiles of all of the organonanoclays were adjusted to three different release-kinetic models, demonstrating the Korsmeyer-Peppas model with release dependence on (i) the organic-inorganic hybrid system, and (ii) the nature of loaded molecules and their interaction with the support. Furthermore, in vitro cell viability assays were carried out with Caco-2 cells, demonstrating that the organonanoclays are well tolerated by cells at particle concentrations of ca. 50 µg/mL.

Fluorogenic Detection of Human Serum Albumin Using Curcumin-Capped Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v/v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.

Antibacterial Activity of Linezolid against Gram-Negative Bacteria: Utilization of ε-Poly-l-Lysine Capped Silica Xerogel as an Activating Carrier.

In recent times, many approaches have been developed against drug resistant Gram-negative bacteria. However, low-cost high effective materials which could broaden the spectrum of antibiotics are still needed. In this study, enhancement of linezolid spectrum, normally active against Gram-positive bacteria, was aimed for Gram-negative bacteria growth inhibition. For this purpose, a silica xerogel prepared from a low-cost precursor is used as a drug carrier owing to the advantages of its mesoporous structure, suitable pore and particle size and ultralow density. The silica xerogel is loaded with linezolid and capped with ε-poly-l-lysine. The developed nano-formulation shows a marked antibacterial activity against to Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. In comparison to free linezolid and ε-poly-l-lysine, the material demonstrates a synergistic effect on killing for the three tested bacteria. The results show that silica xerogels can be used as a potential drug carrier and activity enhancer. This strategy could provide the improvement of antibacterial activity spectrum of antibacterial agents like linezolid and could represent a powerful alternative to overcome antibiotic resistance in a near future.

Simple Endotoxin Detection Using Polymyxin-B-Gated Nanoparticles.

A nanodevice based on mesoporous silica nanoparticles with rhodamine B in the pore framework, functionalized with carboxylates on the outer surface and capped with the cationic polymyxin B peptide, was used to selectively detect endotoxin in aqueous solutions with a limit of detection in the picomolar range.