6 research outputs found
Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier
For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells
PAMAM Dendron Lipid Assemblies That Undergo Structural Transition in Response to Weakly Acidic pH and Their Cytoplasmic Delivery Capability
Dendron
lipids designed to consist of amine-terminated polyamidoamine
G1 dendron and two octadecyl chains were used for the preparation
of pH-responsive molecular assemblies having phase structures that
are changed through their dynamic molecular shape. The dendron lipid
contains two primary amines and two tertiary amines in the dendron
moiety, changing its charged state in the pH region between pH 10
and pH 4. The assemblies were shown to take a vesicle structure at
neutral and alkaline pHs, but their structure changed to a micelle-like
structure below pH 6.4. Because this pH region corresponds to one
in which tertiary amines of the dendron lipid became protonated, protonation
of tertiary amines in addition to primary amines in the dendron moiety
might affect its dynamic molecular shape, resulting in a sharp pH
response of the assemblies. The assemblies tended to form aggregates
when taking on a vesicle form with a gel phase, but incorporation
of a poly(ethylene glycol)–lipid provided dendron lipid vesicles
with both sharp pH response and high colloidal stability. The poly(ethylene
glycol)-incorporated dendron lipid vesicles tightly retained ovalbumin
molecules in their internal aqueous space but released them almost
completely at pH 6.0. In addition, the vesicles were shown to achieve
efficient ovalbumin delivery into cytosol of DC2.4 cells (mouse dendritic
cell line) after internalization through endocytosis
Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system
Transdermal drug delivery systems are a key technology for skin-related diseases and for cosmetics development. The delivery of active ingredients to an appropriate site or target cells can greatly improve the efficacy of medical and cosmetic agents. For this study, liposome-based transdermal delivery systems were developed using pH-responsive phytosterol derivatives as liposome components. Succinylated phytosterol (Suc-PS) and 2-carboxy-cyclohexane-1-carboxylated phytosterol (CHex-PS) were synthesized by esterification of hydroxy groups of phytosterol. Modification of phytosterol derivatives on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes was confirmed by negatively zeta potentials at alkaline pH and the change of zeta potentials with decreasing pH. In response to acidic pH and temperatures higher than body temperature, Suc-PS-containing and CHex-PS-containing liposomes exhibited content release at intracellular acidic compartments of the melanocytes at the basement membrane of the skin. Phytosterol-derivative-containing liposomes were taken up by murine melanoma-derived B16-F10 cells. These liposomes delivered their contents into endosomes and cytosol of B16-F10 cells. Furthermore, phytosterol-derivative-containing liposomes penetrated the 3 D skin models and reached the basement membrane. Results show that pH-responsive phytosterol-derivative-containing DMPC liposomes are promising for use in transdermal medical or cosmetic agent delivery to melanocytes.</p