Le line),(red line), line), and UA-G4K blue blue and UA-G4K (light (lightline). line).Table 4. Linear regressions equations, R2 values, LD50 of G4K, UA and UA-G4K, and SI ranges of of SI for UA and UA-G4K; the SI values computed for each enterococcal isolate regarded as UA and UA-G4K (24 h treatments).Table 4 collects the 3 equations, the linked R2 values, the LD50, plus the rangein this study are observable in Table three.Sample G4K UA UA-G4K EquationsR2 0.9000 0.9606 0.LD50 47.4 54.9 96.SI N.D six.22.5 22.593.y = -0.7300x 84.601 y = -0.8206x 95.040 y = -0.4386x 92.The sufficiently high value of the coefficients of determination R2 (Table four) ensured the linearity of the regressions. Regarding the obtained LD50 values, even though its LD50 was like that of pristine UA, the much more lethal compound was the empty dendrimer G4K. Interestingly, the LD50 of the UA-loaded NPs was 2-fold greater than that of G4K and 1.8-fold higher than that of UA, confirming that by its nano-encapsulation, not only the water solubility of UA was remarkably improved, but additionally its cytotoxicity on HaCaT cells was considerably reduced. In addition, if we look at the amounts of UA that the LD50 of UA-G4K can deliver immediately after 24 h accordingly with its DL and release profile (806.six /mL, 1766.1 ), the UA nanotechnologically manipulated resulted 32.2-fold less cytotoxic than untreated UA. Additionally, considering the LD50 of untreated UA (54.9 ) plus the dose of UA-G4K necessary to provide such amounts of UA (3.0 ), it can be noted that at the obtained concentration of 3.0 , UA-G4K is practically not cytotoxic, leaving alive the 91.two of cells. This means that the UA-loaded formulation obtained by merging UA and G4K, when might be administered at a PHA-543613 Biological Activity dosage capable to release a UA quantity, which, if untreated, kills the 50 of HaCaT cells, are going to be lethal for only the 8.8 of exposed cells. Regarding the SI values of UA (six.22.five) and UA-G4K (22.593.7), they were both considerably larger than those reported as acceptable to think about the new antibacterial agent suitable for therapeutic makes use of. In addition, the SI values in the UA-G4K NPs had been three.61.2-fold greater than these of UA, therefore establishing its higher suitability for biomedical applicationsPharmaceutics 2021, 13,16 ofand as a new therapeutic agent. Also, considering that the UA released by the LD50 of UA-G4K should be 1766.1 , the SI in the nanoengineered UA was within the variety 410.73532.2, that may be 66.285.6-fold higher than that of untreated UA. Concerning the SI values which will be deemed satisfactory, the reported opinions are conflicting. Some authors have hypothesized that SI values 10 make a molecule worthy of additional investigation [75,76], although Weerapreeyakul et al. [77] proposed a reduce SI worth (three) to define a clinically applicable molecule as an anti-cancer agent. In microbiology, Adamu et al. [78,79] reported the antibacterial activities and SI of South African plant leaf extracts, and also the most active extract Moveltipril Angiotensin-converting Enzyme (ACE) showed an SI of five.2. Famuyide et al. [80], who described the antibacterial activity of plant extracts on some Gram-positive and Gram-negative bacteria, stated that the extracts could be regarded bioactive and non-toxic if SI 1, while Nogueira and Estolio do Rosario reported that SI should really not be much less than 2 [81]. On account of these numerous diverging opinions on the SI acceptance criterion, we think that further research are required to ascertain the minimum acceptable SI worth. However, UA-G4K NPs, possessing SI values.