Morphology modulation of polymeric assemblies by guest drug molecules: TEM study and compatibility evaluation

Amphiphilic copolymers with poly(N-isopropylacrylamide) and ethyl tryptophan, ethyl 4-aminobenzoate, or ethyl glycinate as side groups were synthesized. Assemblies based on these copolymers were employed as model systems to investigate the morphology transformation upon loading of various hydrophobic drugs. TEM observation suggested that the loading of non-steroidal anti-inflammatory drugs, including ibuprofen, ketoprofen, indomethacin, naproxen and mefenamic acid, can trigger a significant morphological transformation of assemblies based on copolymers with low substitution of hydrophobic group. On the other hand, the introduction of steroidal anti-inflammatory drugs (medroxyprogesterone acetate, prednisone acetate and dexamethasone) and aliphatic acids (caprylic acid, tetradecanoic acid and stearic acid) has no significant effect on the morphology of assemblies derived from the same copolymers, although they do have some effect on the morphology of assemblies based on copolymers with high content of hydrophobic group. In addition, the morphology of assemblies is well correlated with drug loading efficiency. An occurrence of morphology transformation means a higher drug loading, and vice versa. Various physicochemical parameters including partition coefficient, molecular volume and solubility parameters were calculated according to group contribution method. Analysis of these data pointed to the fact that a combination of molecular volume and solubility parameters can be used as a measure to judge whether one molecule is ‘active’ or ‘neutral’. This rule can also be applied to evaluate the compatibility between candidate drugs and nanocarriers based on these copolymers.