Chlorhexidine/losartan ionic pair binding and its nanoprecipitation: physico-chemical characterisation and antimicrobial activity

Abstract

Chlorhexidine is a widely used, di-cationic, broad-spectrum antimicrobial agent and losartan is a well-known, anionic-specific antagonist of AT1 renin-angiotensin receptor that acts as an anti-hypertensive agent. The combination of these molecules gives a chlorhexidine di-losartanate (ClxLos 2 ) hydrophobic ion pair that spontaneously aggregates into nanoparticles (NPs). This work investigated the formation of ClxLos 2 NPs using the analysis of the solid state by fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry and scanning electron microscopy and in aqueous environment by calorimetric, zeta potential and dynamic light scattering titrations. Furthermore, to demonstrate the potential antimicrobial activity of ClxLos 2 , in vitro antibacterial tests were conducted against Staphylococcus aureus (ATCC 27664), Streptococcus viridans (ATCC 11563) and Enterococcus faecalis (ATCC 14508). Based on these studies, it is proposed that ClxLos 2 could be used for controlled drug release based on ionic dissociation during dilution, thereby avoiding the use of any solid matrix.

Control of size in losartan/copper(II) coordination complex hydrophobic precipitate

“…It shows a continuous weight loss since the heat begins up to 115 °C (11.7%) due dehydration, and a strong weight loss associated to decomposition, starting at 285 °C. In the DSC curve, a total of five thermal events were observed, which were also in accordance with previously published data [37,43,44]. DSC measurements revealed two transitions not associated to weight loss.…”

“…The thermogravimetric profile of KLos was similar to that previously described by some of us [37] and by other authors [43]. It shows a continuous weight loss since the heat begins up to 115 °C (11.7%) due dehydration, and a strong weight loss associated to decomposition, starting at 285 °C.…”

“…Recently, we have proposed a controlled release system based on HP ion pairing formed by the antihypertensive drug losartan and the antimicrobial agent chlorhexidine named ClxLos 2 , which showed improved antimicrobial effect against Enterococcus faecalis [37]. In this system, it was also observed that the chlorhexidine cation was able to modulate the size and charge of the precipitate, in a way to produce nanoparticles of ≈600 nm.…”

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

“…formed a hydrophobic complex from two therapeutic small molecules, cationic chlorhexidine and anionic losartan, but did not encapsulate the result in a separate delivery vehicle. 152 Other papers report choosing their counterion based on therapeutic synergy. Kalhapure et al chose from among several similarly-lipophilic counterions – palmitoleic, oleic, linoleic, linolenic, and arachidonic acid – by checking the ability of each to inhibit S. aureus growth.…”

Study of the interaction between glucosamine hydrochloride and sodium dodecylsulphate micelles using conductometric, isothermal calorimetry, zeta-potential titrations, and NMR NOESY

“…(5)). 27 The analyses were performed in Microcal Origin 5.0 software (for ITC) after subtraction of the blank experiment 27−29…”