As it was expected, SN further enhanced the protection with the APR of 6.7. (Table 4 experiment 4). When DTO was coencapsulated with Rh (Table 4 experiment 5), the APR was 3.9. When DTO was coencapsulated with TS and Rh, (SL-DTO-Rh) the APR was enhanced to 4.9 (Table 4 experiment 6). The highest protection (APR = 15.3) was achieved with the combination of (SL-DTO-TS-Rh) and SN (Table 4 experiment 7). Expressing the relative antidotal potency ratios (RAPR) better indicates the differences

in protection with two antidotal systems (Table 5). Comparing experiment 2 and 3 (RAPR = 2.2) represents the effects of TS coencapsulation with DTO. When comparing experiments 3 and 4 (RAPR = 1.4) or experiments 6 and Inhibitors,research,lifescience,medical 7 (RAPR = 3.1) the enhancement effects reached by SN are represented. The significant enhancement by Rh is expressed when comparing experiments 2 and 5 (RAPR Inhibitors,research,lifescience,medical = 1.8) and experiments 4 and 7 (RAPR = 2.3) confirming earlier studies with other types of encapsulation formulations for Rh [23, 26, 27]. Table 5 Relative

prophylactic antidotal potency ratios (RAPRs) to express enhancing effects by Rh, SN, and coencapsulated TS. Table 6 shows the therapeutic antidotal protection with the (SL-DTO-TS-Rh) combinations with and without SN. At approximately 2 LD50 dose of KCN Inhibitors,research,lifescience,medical (15mg/kg), all the 6 animals survived in each experiment (Table 6 experiments 1, 2, and 3). However, when the KCN

Inhibitors,research,lifescience,medical dose was enhanced (20mg/kg, approximately 3 LD50) the survival rate with (SL-DTO-TS) + SN was 67% (Table 6 experiment 4), while with (SL-DTO-TS) without SN provided a 50% survival rate (Table 6 experiment 6). Selleckchem Cabozantinib However the (SL-DTO-TS-Rh) antidotal system with and without SN also provided a 100% therapeutic protection (Table 6 experiments 5 and 7). Table 6 Therapeutic protection by various CN antidotal combinations. Control: KCN LD50 = 7.8 (4.6–13.1) mg/kg. Inhibitors,research,lifescience,medical 4. Conclusions The present experiments and results are confirming that the approach of utilizing externally administered, encapsulated, metabolizing rhodanese may have broad implications in cyanide antidotal therapy. The application of this approach very has been successfully tested in animal models. In summary, these studies are describing the prophylactic and therapeutic in vivo efficacy of the encapsulated Rh and the new, reactive sulfur donor DTO. Optimization efforts were attempted for the liposomal lipid compositions, Rh-load, and coencapsulation of two sulfur donors (TS and DTO) and Rh to enhance the encapsulation efficiency for the given components. Optimization of the carrier systems is always a major part of these types of research efforts. Considering the high lipophilicity of DTO, for further in vivo applications other introduction routes (e.g., intramuscular) with further formulation optimizations are recommended.