posted on 2024-02-02, 22:49authored byRaquel López-Rios de Castro, Robert M. Ziolek, Martin B. Ulmschneider, Christian D. Lorenz
Polymeric nanoparticles are a highly promising drug delivery
formulation.
However, a lack of understanding of the molecular mechanisms that
underlie their drug solubilization and controlled release capabilities
has hindered the efficient clinical translation of such technologies.
Polyethylene glycol-poly(lactic-co-glycolic) acid
(PEG–PLGA) nanoparticles have been widely studied as cancer
drug delivery vehicles. In this letter, we use unbiased coarse-grained
molecular dynamics simulations to model the self-assembly of a PEG–PLGA
nanoparticle and its solubulization of the anticancer peptide, EEK,
with good agreement with previously reported experimental structural
data. We applied unsupervised machine learning techniques to quantify
the conformations that polymers adopt at various locations within
the nanoparticle. We find that the local microenvironments formed
by the various polymer conformations promote preferential EEK solubilization
within specific regions of the NP. This demonstrates that these microenvironments
are key in controlling drug storage locations within nanoparticles,
supporting the rational design of nanoparticles for therapeutic applications.