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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Quantification of Cellular Drug Biodistribution Addresses Challenges in Evaluating In Vitro and In Vivo Encapsulated Drug Delivery
Advanced therapeutics, v 4(3), pp 2000125-n/a
01 Mar 2021
PMID: 33997266
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nanoencapsulated drug delivery to solid tumors is a promising approach to overcome the pharmacokinetic limitations of therapeutic drugs. However, encapsulation leads to complex drug biodistribution and delivery making analysis of delivery efficacy challenging. As proxies, nanocarrier accumulation or total tumor drug uptake in the tumor are used to evaluate delivery. Yet these measurements fail to assess the delivery of active, released drug to the target, and thus it commonly remains unknown if drug-target occupancy is achieved. Here, an approach to evaluate the delivery of encapsulated drug to the target is developed, where residual drug target vacancy is measured using a fluorescent drug analog. In vitro measurements reveal that burst release governs drug delivery independent of nanoparticle uptake, and highlight limitations of evaluating nanoencapsulated drug delivery in these models. In vivo, however, the approach captures successful nanoencapsulated delivery, showing that tumor stromal cells drive nanoparticle accumulation and mediate drug delivery to adjacent cancer cells. These results, and generalizable approach, provide a critical advance to evaluate delivery of encapsulated drugs to the drug target-the central objective of nanotherapeutics.
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Details
- Title
- Quantification of Cellular Drug Biodistribution Addresses Challenges in Evaluating In Vitro and In Vivo Encapsulated Drug Delivery
- Creators
- Christopher B. Rodell - Center for Systems BiologyPaige Baldwin - Northeastern UniversityBianca Fernandez - Massachusetts General HospitalRalph Weissleder - Harvard UniversitySrinivas Sridhar - Northeastern UniversityJohn Matthew Dubach - Massachusetts General Hospital
- Publication Details
- Advanced therapeutics, v 4(3), pp 2000125-n/a
- Publisher
- Wiley
- Number of pages
- 11
- Grant note
- R00CA198857; R01CA241179; T32CA079443 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000598898000001
- Scopus ID
- 2-s2.0-85100234872
- Other Identifier
- 991019169691004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy