<p> Here, we
describe a simple, efficient formulation of a novel library of
β-cyclodextrin-poly (β-amino ester) networks (CDN) to achieve this goal. We observed that network
architecture was a critical determinant of CDN encapsulation of candidate
molecules, with a more hydrophobic core enabling effective self-assembly and a
PEGylated surface enabling high loading (up to ~30% w/w), effective self
assembly of the nanoparticle, and slow release of drug into aqueous media (24
days) for the model <i>HDACi</i>
panobinostat. Optimized CDN nanoparticles were taken up by GL261 cells in
culture, and released panobinostat was confirmed to be bioactive.
Pharmacokinetic analyses demonstrated that panobinostat was delivered to the
brainstem, cerebellum, and upper spinal cord following intrathecal
administration via cisterna magna injection in healthy mice. We next constructed
a library of CDNs to encapsulate various small, hydrophobic, ionizable
molecules (panobinostat, quisinostat, dacinostat, givinostat, and bortezomib, camptothecin,
nile red, and cytarabine), which yielded important insights into the structural
requirements for effective drug loading and CDN self-assembly. Taken in sum,
these studies present a novel nanocarrier platform for encapsulation of <i>HDACi</i> via both ionic and hydrophobic
interactions, which is an important step toward better treatment of disease via
<i>HDACi</i> therapy.</p>
Magnetic Nanoparticle Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides Complexes for Gene Delivery
