Inventors: T.L. Lowe, Y.S. Kim
PSU
Inv. Disc. No. 2003-2783
Licensing
Contact: Matthew
D. Smith
Technology Summary
Dendrimers have
become increasingly important in controlled drug delivery due to their high
degree of molecular uniformity, narrow molecular weight distribution, specific
size and intriguing structural properties such as internal voids and cavities,
and a highly functional terminal surface.
They hold promise in targeted delivery of anticancer agents, and can
enhance accumulation within the tumor microvasculature, increase extravasation
into tumor tissue and exhibit low systemic toxicity. In addition, dendrimers are also nanoparticles. In vitro
and in vivo experiments have shown that nanoparticles might have
long blood circulation times and a low reticuloendothelial system (RES) uptake.
They were able to strongly interact with the brain blood vessel endothelial cells of mice, and then be taken up by these
cells by endocytosis. Bound drugs, such as nerve growth factor (NGF), as intact
molecules were then released and exhibited their pharmacological action on the
central nervous system (CNS). Others’
attempt in synthesizing biodegradable dendrons have resulted in polymers that
are neither thermo-responsive nor bona fide dendrimers. In fact, the most common methods of
encapsulating and delivering NGF under development involve the use of organic
solvents, which have adverse effects on the NGF.
Penn State researchers have developed a novel
synthesis process and compositions of several patent pending
“Intelligent Polymers” which are both biodegradable and
thermal-responsive. The Intelligent
Polymers are comprised of poly (N-isopropylacrylamid) (“PNIPAAM”) as the
thermal-responsive unit, poly (L-lactic acid) (“PLLA”) as the biodegradable
hydrophobic unit, and a pH-sensitive poly(L-lysine) (“PLL”) dendron
domain. Penn State’s Intelligent
Polymers have been tested in preliminary studies to be effective multi-stimuli-responsive
biodegradable polymeric materials.
Acute thermal-responsiveness
Complete biodegradation
Controlled and sustained release of growth
factor
3-dimensional scaffolding and proper
microenvironment fostering cell growth
Penn State’s patent pending Intelligent Polymers,
and their synthesis processes, can be manipulated and adapted to suit a variety
of clinical needs. They can serve as a
targeted, sustained and controlled drug delivery system, dispensing proteins,
genes and/or small molecule therapeutics.
Their acute bio-responsiveness allows for fewer administration and
maintenance of drug levels, and eliminates potential for under- or
overdosing. Intelligent Polymers can
also serve as biocompatible polymer for cell scaffolding packed with drugs or
growth factors needed to enhance tissue or organ repair. Complete biodegradability eliminates
unnecessary secondary surgical procedures and adverse physical reactions to
un-degraded by-products.