Antimicrobial Nanogels with Nanoinjection Capabilities for Delivery of the Hydrophobic Antibacterial Agent Triclosan

Abstract

With the ever-growing problem of antibiotic resistance, developing antimicrobial strategies is urgently needed. Herein, a hydrophobic drug delivery nanocarrier is developed for combating planktonic bacteria that enhances the efficiency of the hydrophobic antimicrobial agent, Triclosan, up to a 1000 times. The poly( N -isopropylacrylamide- co - N -[3-(dimethylamino)propyl]methacrylamide), p(NIPAM- co -DMAPMA), based nanogel is prepared via a one-pot precipitation polymerization, followed by quaternization with 1-bromododecane to form hydrophobic domains inside the nanogel network through intraparticle self-assembly of the aliphatic chains (C12). Triclosan, as the model hydrophobic antimicrobial drug, is loaded within the hydrophobic domains inside the nanogel. The nanogel can adhere to the bacterial cell wall via electrostatic interactions and induce membrane destruction via the insertion of the aliphatic chains into the cell membrane. The hydrophobic antimicrobial Triclosan can be actively injected into the cell through the destroyed membrane. This approach dramatically increases the effective concentration of Triclosan at the bacterial site. Both the minimal inhibitory concentration and minimal bactericidal concentration against the Gram-positive bacteria S. aureus and S. epidermidis decreased 3 orders of magnitude, compared to free Triclosan. The synergy of physical destruction and active nanoinjection significantly enhances the antimicrobial efficacy, and the designed nanoinjection delivery system holds great promise for combating antimicrobial resistance as well as the applications of hydrophobic drugs delivery for many other possible applications.

Highly Efficient Antimicrobial and Antifouling Surface Coatings with Triclosan-Loaded Nanogels

“… 42 , 43 These intraparticle micelles facilitate the encapsulation of hydrophobic components such as Triclosan, as shown in suspension in previous research. 37 To achieve the Triclosan incorporation on the coated surface, a previously prepared Q-nGel bound glass substrate is immersed in a Triclosan solution. Figure 3 c shows the coating pattern with a high surface coverage of the nanogel layer after the Triclosan loading.…”

“…Triclosan is a hydrophobic molecule with a similar molecular weight to Nile Red and was previously shown to behave similarly within these particles. 37 …”

“…Although the exact killing mechanism of QACs is still not completely understood, it is accepted that positively charged surfaces with quaternary-ammonium functionalities kill attached bacteria by disrupting the membrane when the contact occurs between the negatively charged bacterial membrane and positively charged QACs. 34 − 36 Recently, we have introduced QACs with long alkyl chains into nanogels to induce killing of bacteria in suspension, 37 which was more effective than using previously designed quaternization approaches using methyl iodide. 25 Upon introducing the longer alkyl chain, we found that a more sophisticated killing effect was achieved due to the formation of intraparticle micelles, which facilitated the storage of Triclosan, a hydrophobic antimicrobial that only was released when coming into contact with bacteria and displayed a synergistic killing effect.…”

β-Cyclodextrin/Triclosan Complex-Grafted Methacrylated Glycol Chitosan Hydorgel by Photocrosslinking via Visible Light Irradiation for a Tissue Bio-Adhesive

“…A gradual increase in cell proliferation was observed in all samples for 7 days. TCS is known to have cytocompatibility below the concentration of 5 µg/mL, but above the concentration, it induces cytotoxicity by stimulating apoptosis [ 27 , 28 ]. Considering this fact, the concentration (1.8 µg/mL) of TCS used in this study is within biocompatible range.…”

“…From our result, together with the antibacterial activity of MGC, almost 30% of TCS release showed improved antibacterial activity. In addition, to accelerate antibacterial activity, TCS must have a concentration of above 5 µg/mL [ 28 ]. From this result, 1.8 µg of TCS containing MGC-g-CD exhibited excellent antibacterial activity.…”