Biodegradable nanocarriers coated with polymyxin B: Evaluation of leishmanicidal and antibacterial potential

Abstract

Most treatments of leishmaniasis require hospitalization and present side effects or parasite resistance; innovations in drug formulation/reposition can overcome these barriers and must be pursued to increase therapeutic alternatives. Therefore, we tested polymyxin B (polB) potential to kill Leishmania amazonensis , adsorbed or not in PBCA nanoparticles (PBCAnp), which could augment polB internalization in infected macrophages. PBCAnps were fabricated by anionic polymerization and analyzed by Dynamic Light Scattering (size, ζ potential), Nanoparticle Tracking Analysis (size/concentration), vertical diffusion cell (release rate), drug incorporation (indirect method, protein determination) and in vitro cell viability. Nanoparticles coated with polB (PBCAnp-polB) presented an adequate size of 261.5 ± 25.9 nm, low PDI and ζ of 1.79 ± 0.17 mV (stable for 45 days, at least). The 50% drug release from PBCAnp-polB was 6–7 times slower than the free polB, which favors a prolonged and desired release profile. Concerning in vitro evaluations, polB alone reduced in vitro amastigote infection of macrophages (10 μg/mL) without complete parasite elimination, even at higher concentrations. This behavior limits its future application to adjuvant leishmanicidal therapy or antimicrobial coating of carriers. The nanocarrier PBCAnp also presented leishmanicidal effect and surpassed polB activity; however, no antimicrobial activity was detected. PolB maintained its activity against E . coli , Pseudomonas and Klebsiella , adding antimicrobial properties to the nanoparticles. Thus, this coated drug delivery system, described for the first time, demonstrated antileishmanial and antimicrobial properties. The bactericidal feature helps with concomitant prevention/treatment of secondary infections that worst ulcers induced by cutaneous L . amazonensis , ultimately ending in disfiguring or disabling lesions.

Nanomedicine-based strategies to improve treatment of cutaneous leishmaniasis

“…To overcome barriers of parasite resistance to treatment, unwanted side effects from current leishmaniasis medications and microbial wound infections, Costa et al . [137] formulated non-cytotoxic biodegradable polybutylcyanoacrylate nanoparticles coated with polymyxin B (PBCAnp-polB) which expressed both anti-leishmanial and antimicrobial activity. Inhibition of L. amazonensis promastigotes were promoted by the PBCA nanoparticles.…”

“…Inhibition of L. amazonensis promastigotes were promoted by the PBCA nanoparticles. Moreover, the polymyxin B bound to the nanoparticles stayed active and was responsible for the antibacterial activity against E. coli, P. aeruginosa and K. pneumoniae [137]. Titanium dioxide (TiO 2 ) and silver oxide (Ag 2 O) nanoparticles were also reported to have anti-leishmanial activity with simultaneous high microbial growth inhibition properties [138].…”

Functionalized Particles Designed for Targeted Delivery

“…Nucleic acids from well-defined living organisms not only are too expensive to be used on a large scale for drug encapsulation but, what is even more im- Poly(alkylcyanoacrylate) nanoparticles and nanoparticles containing copolymers with poly(alkylcyanoacrylate) blocks were used as carriers of bioactive substances. Here we cite only some original papers published during the last ten years [116][117][118][119][120] and some comprehensive reviews covering this subject [121][122][123][124][125][126].…”

Polymyxin Delivery Systems: Recent Advances and Challenges

“…Synthetic polyanionic macromolecules have also been used to design polymyxin delivery systems. For example, Costa et al [110] fabricated poly-butyl-cyanoacrylate-based nanoparticles of polymyxin B (217 nm in size, with a surface charge of −18 mV), and found them effective in the treatment of leishmaniasis and associated Gram-negative bacterial infections. The release profile of polymyxin from the nanoparticles (into PBS, pH 7.4) was 50% of the loaded drug in 6 h, which was 6-7 times slower than observed with free polymyxin.…”