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Angew Chem Int Ed Engl. 2016 Mar 1;55(10):3309-12. doi: 10.1002/anie.201509183. Epub 2016 Feb 5.

Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins.

Author information

1
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
2
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
3
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
4
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. huangyuan0@163.com.
5
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. jshi@bwh.harvard.edu.
6
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. ofarokhzad@bwh.harvard.edu.
7
King Abdulaziz University, Jeddah, Saudi Arabia. ofarokhzad@bwh.harvard.edu.

Abstract

Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.

KEYWORDS:

drug delivery; insulin; nanoparticles; polymers; transcytosis

PMID:
26846161
PMCID:
PMC4835185
[Available on 2017-03-01]
DOI:
10.1002/anie.201509183
[Indexed for MEDLINE]
Free PMC Article

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