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Nanomedicine (Lond). 2017 Apr;12(7):729-743. doi: 10.2217/nnm-2016-0375. Epub 2017 Mar 21.

Surface modulation of polymeric nanocarriers enhances the stability and delivery of proteins and small molecules.

Author information

1
Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
2
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

AIM:

We aimed to enhance the stability and therapeutic efficiency of protein-based therapeutic formulations.

MATERIALS & METHODS:

Proteins were immobilized on the surface of nanoparticles (NPs) to improve both protein stability and protein function, especially enzymatic activity. The modularity of the platform was demonstrated by coating proteins of varied molecular weights and functionalities on the surface of poly(lactic-co-glycolic acid)-based NPs.

RESULTS:

Coating proteins to the particle surface greatly enhanced the stability of the NPs, preventing particle aggregation and improving enzymatic potency, including in vivo. Specifically, coating of collagenase I to the particle surface greatly improved the ability of the enzyme to degrade tumor collagen relative to free enzyme, thereby increasing the penetration of adjuvant chemotherapy (doxorubicin). Additionally, the protein coating reduced the rate of doxorubicin release, enabling sustained release of the small-molecule payload.

CONCLUSION:

The straightforward procedure described herein permits the formulation of modular NPs that can combine and sustain the benefits of small molecules and biologics.

KEYWORDS:

PLGA; drug delivery; nanoparticle; proteins; small molecules; stability

PMID:
28322107
DOI:
10.2217/nnm-2016-0375
[Indexed for MEDLINE]

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