Abstract
The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer.
Highlights
Mycobacteria and target cells, it appears that clumps should be avoided
We observed that if the mycobacteria were blended with the oil that was already mixed with the surfactant, the emulsion was more homogeneous (Fig. 1c)
The olive oil (OO) emulsion maintains the highest proportion of M. brumae viable cells, whereas the mineral oil (MO) emulsion better disaggregates the M. brumae clumps
Summary
Mycobacteria and target cells, it appears that clumps should be avoided. obtaining homogenous mycobacteria suspensions could influence their antitumor effect. One of the possible strategies is the formulation of oil-in-water (O/W) or water-in-oil (W/O) mycobacteria emulsions, which have been developed for different types of compounds to enhance the induced immune response of antitumor agents or adjuvants[13]. An O/W preparation of mytomycin, a chemotherapy agent that is used for intravesical BC treatment, has recently been conducted to enhance its antitumor effect. In the case of mycobacteria, researchers who have proposed the use of heat-killed mycobacteria or cell wall extracts for cancer treatment or as adjuvants have developed formulations using oils. In the case of BC, treatment with live mycobacteria is required to obtain an optimum antitumor effect[9,8]. We aimed to demonstrate the ability of this formulation to trigger an proper immune response and to inhibit bladder tumor growth both in vitro and in vivo
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