1 research outputs found
Solubilization of Therapeutic Agents in Micellar Nanomedicines
We use atomistic molecular dynamics
simulations to reveal the binding
mechanisms of therapeutic agents in PEG-ylated micellar nanocarriers
(SSM). In our experiments, SSM in buffer solutions can solubilize
either ≈11 small bexarotene molecules or ≈6 (2 in low
ionic strength buffer) human vasoactive intestinal peptide (VIP) molecules.
Free energy calculations reveal that molecules of the poorly water-soluble
drug bexarotene can reside at the micellar ionic interface of the
PEG corona, with their polar ends pointing out. Alternatively, they
can reside in the alkane core center, where several bexarotene molecules
can self-stabilize by forming a cluster held together by a network
of hydrogen bonds. We also show that highly charged molecules, such
as VIP, can be stabilized at the SSM ionic interface by Coulombic
coupling between their positively charged residues and the negatively
charged phosphate headgroups of the lipids. The obtained results illustrate
that atomistic simulations can reveal drug solubilization character
in nanocarriers and be used in efficient optimization of novel nanomedicines