Dextran Vesicular Carriers for Dual Encapsulation of Hydrophilic and Hydrophobic Molecules and Delivery into Cells

Dextran vesicular nanoscaffolds were developed based
on polysaccharide
and renewable resource alkyl tail for dual encapsulation of hydrophilic
and hydrophobic molecules (or drugs) and delivery into cells. The
roles of the hydrophobic segments on the molecular self-organization
of dextran backbone into vesicles or nanoparticles were investigated
in detail. Dextran vesicles were found to be a unique dual carrier
in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic
anticancer drug (camptothecin, CPT) were selectively encapsulated
in the hydrophilic core and hydrophobic layer, respectively. The dextran
vesicles were capable of protecting the plasma-sensitive CPT lactone
pharmacophore against the hydrolysis by 10× better than the CPT
alone in PBS. The aliphatic ester linkage connecting the hydrophobic
tail with dextran was found to be cleaved by esterase under physiological
conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the
dextran vesicle and its drug conjugate were tested on mouse embryonic
fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold
was found to be nontoxic to living cells. CPT loaded vesicles were
found to be 2.5-fold more effective in killing fibroblasts compared
to that of CPT alone in PBS. Confocal microscopic images confirmed
that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts
compared to CPT alone, showing a distinctly perinuclear localization
in cells. The custom designed dextran vesicular provides new research
opportunities for dual loading and delivering of hydrophilic and hydrophobic
drug molecules.