John Garner

PLGA and PLGA-rhodamine from PolySciTech used in study on chemotherapeutic delivery by nanoparticles

Blog Post created by John Garner on Nov 15, 2017

Park, 2017 PLGA-chitosan comparative imaging.jpg

For conventional, loose-drug, chemotherapy, less than 1% of the injected medicine actually makes it to the tumor site. The clinical method for solving this problem has been to inject massive doses of chemotherapeutic agents to the patient, in the hopes that at least some of the medicine makes it to the tumor. This is not a good solution to this problem and leads to substantial morbidity from the side-effects of chemotherapy (hair loss, immune-system damage, etc.). Nanoparticle-based technologies have been developed in the hopes of creating a system in which the drug is encapsulated in a small particle that flows through the blood until it is entrapped by the tumor. Although coating the particle with PEG improves its circulation time, it can also hinder uptake by the tumor. Recently, researchers from Purdue University and Eli Lilly and Company used PLGA (PolyVivo AP020) and Rhodamine-labelled PLGA (Polyvivo AV011) from PolySciTech (www.polyscitech.com) to develop chitosan-coated nanoparticles with preferential tumor attraction over PEGylated nanoparticles. They found, however, that although the particles were preferentially absorbed by the polymer, the drug itself (in the study, ICG tracer-dye was used) leached out too quickly to be of any use. This highlights how critical the drug-entrapment strategy is to the overall design of a nanoparticle formulation. This research holds promise to provide for improved chemotherapeutic strategies with reduced side-effects. Read more: Park, Jinho, Yihua Pei, Hyesun Hyun, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309367

 

“Abstract: For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs. Keywords: pH-responsive Drug delivery PLGA nanoparticles Small molecules In vivo imaging Encapsulation stability”

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