Wednesday, November 14, 2018

Block-copolymers from PolySciTech used in the development of nano-emulsion based ultra-sound mediated noninvasive targeted drug delivery

Due to the circulatory nature of the human bloodstream, any agent introduced into the bloodstream at any location is quickly spread throughout the human body. This is good for drugs which need to be spread throughout the human body (i.e. systemic dosage) however is not very efficient for drugs whose location of action is only in one particular region. Researchers at Stanford University and Massachusetts General Hospital used several PEG-PCL, PEG-PLA, PEG-PLGA copolymers (Polyvivo AK073, AK001, AK052, AK090, AK004, and AK003) from PolySciTech (www.polyscitech.com) to generate nanoparticles with perfluorocarbons that could be activated using ultrasound. In this way the drug can be administered systemically but then released (uncaged) in the desired location of action. This research holds promise to enable targeted drug delivery with minimal side-effects. Read more: Zhong, Qian, Byung C. Yoon, Muna R. Aryal, Jeffrey B. Wang, Ananya Karthik, and Raag D. Airan. "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." bioRxiv (2018): 315044. https://www.biorxiv.org/content/early/2018/09/10/315044.short

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.”

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