17 research outputs found
Solubility and Density of Potassium Iodide in Binary EthanolâWater Solvent Mixture at (298.15, 303.15, 308.15, and 313.15) K
Solubility and Density of Potassium Iodide in Binary EthanolâWater Solvent Mixture at (298.15, 303.15, 308.15 and 313.15) K
MMP-9 Responsive PEG Cleavable Nanovesicles for Efficient Delivery of Chemotherapeutics to Pancreatic Cancer
MMPâ9 Responsive PEG Cleavable Nanovesicles for Efficient Delivery of Chemotherapeutics to Pancreatic Cancer
Significant differences in biochemical
parameters between normal
and tumor tissues offer an opportunity to chemically design drug carriers
which respond to these changes and deliver the drugs at the desired
site. For example, overexpression of the matrix metalloproteinase-9
(MMP-9) enzyme in the extracellular matrix of tumor tissues can act
as a trigger to chemically modulate the drug delivery from the carriers.
In this study, we have synthesized an MMP-9-cleavable, collagen mimetic
lipopeptide which forms nanosized vesicles with the POPC, POPE-SS-PEG,
and cholesteryl-hemisuccinate lipids. The lipopeptide retains the
triple-helical conformation when incorporated into these nanovesicles.
The PEG groups shield the substrate lipopeptides from hydrolysis by
MMP-9. However, in the presence of elevated glutathione levels, the
PEG groups are reductively removed, exposing the lipopeptides to MMP-9.
The resultant peptide-bond cleavage disturbs the vesiclesâ
lipid bilayer, leading to the release of encapsulated contents. These
PEGylated nanovesicles are capable of encapsulating the anticancer
drug gemcitabine with 50% efficiency. They were stable in physiological
conditions and in human serum. Effective drug release was demonstrated
using the pancreatic ductal carcinoma cells (PANC-1 and MIAPaCa-2)
in two-dimensional and three-dimensional âtumor-likeâ
spheroid cultures. A reduction in tumor growth was observed after
intravenous administration of the gemcitabine-encapsulated nanovesicles
in the xenograft model of athymic, female nude mice