Highly Sustained Release of Bactericides from Complex Coacervates

Abstract

Materials for preventing harmful bacterial contamination attract widespread interest in areas that include healthcare, home/personal care products, and crop protection. One approach to achieving this functionality is through the sustained release of antibacterial compounds. To this end, we show how putty-like complex coacervates, formed through the association of poly­(allylamine hydrochloride) (PAH) with pentavalent tripolyphosphate (TPP) ions, can provide a sustained antibacterial effect by slowly releasing bactericides. Using triclosan (TC) as a model bactericide, we demonstrate that, through their dispersion in the parent PAH solution with nonionic surfactants, hydrophobic biocides can be efficiently and predictably encapsulated within PAH/TPP coacervates. Once encapsulated, the bactericide can be released over multiple months, and the release rates can be readily tuned by varying the bactericide and surfactant compositions used during encapsulation. Through this release, the PAH/TPP coacervates provide sustained bactericidal activity against model Gram-positive and Gram-negative bacteria (Staphylococcus aureus and Escherichia coli) grown under a nutrient-rich condition over at least two weeks. Thereafter, though some partial activity persists after one month, the release slows down and the bactericide-eluting coacervates lose their efficacy. Overall, we show that bactericide release from easy-to-prepare complex coacervates can provide a pathway to sustained disinfection.

Accelerating Payload Release from Complex Coacervates through Mechanical Stimulation

“…This swelling caused the coacervate weight to monotonically increase with time and the coacervate pellets to increase in size and become wispy (see Figure 3 bi). Such a response to deionized water was qualitatively consistent with that seen for polyanion/polycation coacervates (complexes of oppositely charged polyelectrolytes) in deionized water [ 32 , 33 ], and bactericide-loaded PAH/TPP coacervates in tap water [ 21 , 27 ], and—together with the continued slow release from these coacervates in Figure 2 —suggested that the swollen coacervates were composed of water-rich pores dispersed in a continuous coacervate phase. These pores were likely gradually generated due to (1) the high osmotic pressure created by the encapsulated RhB and (possibly) unassociated PAH and TPP, and (2) the greater permeability of the (much smaller) water molecules through the coacervate phase, which allowed the water from the release medium to fill these pores.…”

“…The colloid-rich coacervate phase typically has viscoelastic fluid- or gel-like properties [ 4 , 5 , 6 ], and offers numerous benefits: easy formation under mild, aqueous conditions [ 7 , 8 ]; low toxicity [ 9 , 10 ]; and an ability to form, transform their properties, and dissolve in response to external stimuli [ 1 , 11 , 12 , 13 ]. Among their many potential applications (which range from drug delivery [ 8 , 14 , 15 ] to separation processes [ 16 , 17 ], foods [ 18 ], and adhesives [ 11 , 19 , 20 ]), complex coacervates are frequently used in the controlled release of various active compounds [ 8 , 14 , 15 , 21 , 22 , 23 ].…”

“…This barrier property enables them to sustain the release of small water-soluble molecules (which tend to elute rapidly from gels) over highly extended timescales. Complex coacervates formed from poly(allylamine hydrochloride) (PAH) complexed with the multivalent anion tripolyphosphate (TPP), for instance, have recently been shown to sustain the release of diverse small molecules (including drugs and disinfectants) over multiple months [ 9 , 15 , 21 , 27 ].…”

“…While the highly sustained release enabled by these viscoelastic materials could be useful in an array of biomedical, household, and industrial technologies, the duration of the benefits derived from such release can sometimes be limited by the payload delivery ultimately becoming too slow to be efficacious (once the most-accessible portion of their payload closest to the surface is released) [ 21 , 27 ]. A recent study, for instance, revealed that, while the long-term bactericide release from PAH/TPP coacervates can provide antibacterial benefits over multiple weeks, this activity is ultimately lost (even though only a fraction of the bactericidal payload is released) [ 21 ]. The evident reason for this ultimate activity loss is that the release rate declines with time and, after a few weeks, becomes too slow to be effective.…”

Balance of Macrophage Activation by a Complex Coacervate-Based Adhesive Drug Carrier Facilitates Diabetic Wound Healing

“…Although its use in medicine is more recent, it has been widely applied in the food industry and for personal care since the early 20th century [ 22 , 23 , 24 ]. The advantages of using a complex coacervate as a controlled release system are significant [ 21 , 25 ]. For example, it provides in situ formation in the aqueous environment without a toxic solvent and shear thinning property, making it suitable for injection.…”