For instance, when PS + US were used to deliver 5-FU, the antitumor effect was augmented dramatically for this drug, with a 60% growth rate reduction and enhanced necrosis throughout the tumors as observed by histology. Another in vivo study showed that polystyrene nanoparticles
decrease cavitation threshold in water, and application of this drug delivery technique substantially improved the efficacy of cancer therapy in nude mice with colon tumors when US was used in combination with polymer NP injections [20]. Gene Delivery Inhibitors,research,lifescience,medical by Polymeric PLGA Nanoparticles. — Several studies have shown efficient US-enhanced gene delivery using polyplexes of DNA and cationic-derivatized natural polymers, such as cationized dextran [22] and gelatin [23]. In these experiments, 3MHz US (2 W/cm2, 10% duty cycle) typically was applied for 1 to 2 minutes transdermally to various tissues in Inhibitors,research,lifescience,medical vivo such as tumors or muscle. Insonation always enhanced gene expression for a few days. The authors speculated that cavitation-induced cell membrane damage and permeation were responsible for the enhanced gene expression. Arguably, superior polymeric OSI-906 clinical trial nanoparticle formulations for gene delivery using US may be composed of PLGA, a polymer
approved by the FDA for its excellent profile of biodegradability, Inhibitors,research,lifescience,medical drug biocompatibility, suitable biodegradation kinetics, mechanical Inhibitors,research,lifescience,medical properties, and ease of processing (reviewed in [24]). PLGA and its derivatives have been the center focus for developing nano/microparticles encapsulating therapeutic drugs in a biodegradable format. Many macromolecular drugs including proteins, peptides, genes, vaccines, antigens, and human growth factors can be incorporated successfully into PLGA- or PLGA/PLA-based nano/microparticles. And several microparticle formulations already are available in the market (reviewed in [25]). However, intense research is ongoing to refine and enhance PLGA-based Inhibitors,research,lifescience,medical NP
over other delivery systems, including developing 4-Aminobutyrate aminotransferase blends of PLGA with other polymers, for example, chitosan, pectin, poly(propylene fumarate), poloxamers and poloxamines, polypyrroles, gelatin, poly(vinyl alcohol) (PVA), PVA-chitosan-PEG, and poly(ortho-esters) (reviewed in [25]). These novel technologies can produce PLGA- and PLGA-based nano/microparticles for drug delivery and can dramatically expand the new field for efficient drug/gene delivery if the nanoparticles can be rendered echogenic or acoustically active. Biodegradable PLGA NPs can sustain delivery of drugs, proteins, peptides, and plasmid DNA, owing to their ability to protect macromolecules from degradation in endolysosomes (reviewed in [26]).