Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency.
Encapsulation of small-molecule drugs in hydrophobic polymers or amphiphilic copolymers has been extensively used for preparing polymeric nanoparticles (NPs). The loadings and loading efficiencies of a wide range of drugs in polymeric NPs, however, tend to be very low. In this Communication, we report a strategy to prepare polymeric NPs with exceptionally high drug loading (>50%) and quantitative loading efficiency. Specifically, a dimeric drug conjugate bearing a trigger-responsive domain was designed and used as the core-constructing unit of the NPs. Upon co-precipitation of the dimeric drug and methoxypoly(ethylene glycol)-block-polylactide (mPEG-PLA), NPs with a dimeric drug core and a polymer shell were formed. The high-drug-loading NPs showed excellent stability in physiological conditions. No premature drug or prodrug release was observed in PBS solution without triggering, while external triggering led to controlled release of drug in its authentic form.
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Kaimin
K
Cai
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.|‡Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Xi
X
He
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Ziyuan
Z
Song
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Qian
Q
Yin
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Yanfeng
Y
Zhang
§Division of Hematology-Oncology, Systems Immunobiology Laboratory, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California 90027, United States.|⊥Department of Pediatrics and Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, California 90027, United States.
Fatih M
FM
Uckun
‡Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.
Chen
C
Jiang
†Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Jianjun
J
Cheng
D019281:Dimerization; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D004337:Drug Carriers; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols