Study of Interaction Between PEG Carrier and Three Relevant Drug Molecules: Piroxicam, Paclitaxel, and Hematoporphyrin

Molecular dynamics simulation has been used to study
the specific
interactions between poly­(ethylene glycol) (PEG) and three drug molecules
for which PEG is used to aid delivery: paclitaxel and piroxicam, where
PEG is a carrier agent, and hematoporphyrin, where PEG is covalently
attached to form a “stealth shield”. Simulating at physiological
salt concentration, we found no evidence of any specific interaction
between paclitaxel or piroxicam with PEG, but found a strong interaction
for the case of hematoporphyrin. This interaction is lipophilic in
nature, between the nonpolar (CH2)2 groups of
the PEG and the porphin ring of the hematoporphyrin. This interaction
was found to be strong enough that the PEG aggregated to the hematoporphyrin,
independent of whether or not it was covalently bound. Interestingly,
when the simulation was repeated in absence of salt we found evidence
of this interaction being weakened. This led us to hypothesize a previously
unforeseen mechanism: interaction with salt cations cause the PEG
to coil around the salt ions, each ion binding to many PEG oxygens,
increasing the exposure of the nonpolar ethylene groups, thus increasing
the effective hydrophobicity of PEG. The Hydrophobic ethylene groups
of the PEG chains adhere strongly to the hydrophobic porphin ring.
Experiments involving absorption spectra measurements were conducted,
and these results also indicated that presence of salt at physiological
level increases the effective attractive interaction between PEG and
hematoporphyrin. Taken together, our results demonstrate that while
PEG, due to its solubility in both polar and nonpolar solvents, may
act as a dissolution aid for paclitaxel and piroxicam, of the three
drug molecules studied it will only have a protective role for the
case of the hematoporphyrin.