Ultrasound-sensitive nanoparticle aggregates for targeted drug delivery. Biomaterials 2017 Sep;139:187-194
Date
06/16/2017Pubmed ID
28618348DOI
10.1016/j.biomaterials.2017.06.003Scopus ID
2-s2.0-85020633088 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
Here we describe injectable, ultrasound (US)-responsive, nanoparticle aggregates (NPAs) that disintegrate into slow-release, nanoscale, drug delivery systems, which can be targeted to selective sites by applying low-energy US locally. We show that, unlike microbubble based drug carriers which may suffer from stability problems, the properties of mechanical activated NPAs, composed of polymer nanoparticles, can be tuned by properly adjusting the polymer molecular weight, the size of the nanoparticle precursors as well as the percentage of excipient utilized to hold the NPA together. We then apply this concept to practice by fabricating NPAs composed of nanoparticles loaded with Doxorubicin (Dox) and tested their ability to treat tumors via ultrasound activation. Mouse studies demonstrated significantly increased efficiency of tumor targeting of the US-activated NPAs compared to PLGA nanoparticle controls (with or without US applied) or intact NPAs. Importantly, when the Dox-loaded NPAs were injected and exposed to US energy locally, this increased ability to concentrate nanoparticles at the tumor site resulted in a significantly greater reduction in tumor volume compared to tumors treated with a 20-fold higher dose of the free drug.
Author List
Papa AL, Korin N, Kanapathipillai M, Mammoto A, Mammoto T, Jiang A, Mannix R, Uzun O, Johnson C, Bhatta D, Cuneo G, Ingber DEAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBiocompatible Materials
Cell Line, Tumor
Doxorubicin
Drug Carriers
Drug Delivery Systems
Drug Liberation
Excipients
Lactic Acid
Mice
Mice, Inbred BALB C
Microbubbles
Molecular Weight
Nanoparticles
Neoplasms
Particle Size
Polyglycolic Acid
Polymers
Ultrasonics