954kcal/mol for the PLA-MTX complex. This spatial preference of MAA over PLA is also depicted in the Figure 15 where upon deeper inspection revealed the close proximity of the MTX and MAA molecules. This was further confirmed by the surface-to-volume ratios (SVR) of the complexes with MAA-MTX having a lower SVR value than PLA-MTX (Table 5). The lower the SVR, the more stable the complex structure.
Furthermore, a significant contribution was also provided by the strong H-bonding in MAA-MTX with a bond length of 2.6454Å Inhibitors,research,lifescience,medical and the energy value exceeding nearly 50 times compared to PLA-MTX. These interactions involving the nonbonded attractive forces may induce dipoles in the complex where the binding energy transitions may be proportional to the polarizability of the substituents. These are in
turn proportional to the molar refractivity values where the structure with the lower index of refraction is more stable. MAA-MTX was hence highly stabilized in comparison Inhibitors,research,lifescience,medical to the PLA-MTX with reference to refractivity (Table 6). Figure 15 Energy-minimized geometrical preferences of the MTX-PLA-MAA complexes derived from molecular mechanics computations: (a) MAA-MTX, (b) PLA-MTX, and (c) depiction of adsorption of MTX on MAA nanoparticle (brown colored-tube rendered). MTX is rendered in … Table 6 Computed energy parameters (kcal/mol) of the complexes involving Inhibitors,research,lifescience,medical PLA, MAA, and MTX. These findings corroborated with the MTX-loading capacity that proved that MTX could be adsorbed onto the PLA-MAA nanoparticle surface. In addition, FTIR results were confirmed via the formation of amide linkages between the C-ON-H groups of MTX and MAA/PLA, respectively. Although the PLA-MTX complex Inhibitors,research,lifescience,medical was less stable, the energy
values, molecular attributes, and geometrical orientation were relatively comparable to the MAA-MTX complex. The MTX molecule Inhibitors,research,lifescience,medical displaying an energy-minimized extended conformation was superimposed onto a folded PLA molecule (Figure 15). Deeper inspection of the system revealed that the N2 atoms of MTX were in close interaction with the O2 atoms of the COO-groups of the PLA oligomer. These findings support the hypothesis of charge-dipole crotamiton and dipole-dipole interactions between MTX and the polymers. This also explains the high efficacy of the PLA-MAA nanoparticles to adsorb MTX. 4. Conclusions Various formulations of PLA-MAA nanoparticles were successfully prepared by a double emulsion solvent evaporation technique using a randomized Box-Behnken statistical www.selleckchem.com/products/BAY-73-4506.html design template. The requisite variables required for producing an optimized MTX-loaded PLA-MAA nanoparticle formulation with the desirable response parameters were elucidated by desirability plots. The difference between the actual and desirable response values was minimal.