Polyethylene glycol-b-poly(lactic acid) polymersomes as vehicles for enzyme replacement therapy

Jessica M Kelly; Amanda L Gross; Douglas R Martin; Mark E Byrne

doi:10.2217/nnm-2017-0221

Polyethylene glycol-b-poly(lactic acid) polymersomes as vehicles for enzyme replacement therapy

Nanomedicine (Lond). 2017 Dec;12(23):2591-2606. doi: 10.2217/nnm-2017-0221. Epub 2017 Nov 7.

Authors

Jessica M Kelly^{1

2

3}, Amanda L Gross^{2

4}, Douglas R Martin^{2

3

4}, Mark E Byrne^{1

3

5}

Affiliations

¹ Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, Auburn, AL 36849, USA.
² Scott Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
³ US Department of Education GAANN Graduate Fellowship Program in Biological & Pharmaceutical Engineering, Auburn University, Auburn, AL 36849, USA.
⁴ Department of Anatomy, Physiology, & Pharmacology, Scott Ritchey Research Center, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
⁵ Biomimetic & Biohybrid Materials, Biomedical Devices, & Drug Delivery Laboratories, Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA.

PMID: 29111890
DOI: 10.2217/nnm-2017-0221

Abstract

Aim: Polymersomes are created to deliver an enzyme-based therapy to the brain in lysosomal storage disease patients.

Materials & methods: Polymersomes are formed via the injection method using poly(ethylene glycol)-b-poly(lactic acid) (PEGPLA) and bound to apolipoprotein E, to create a brain-targeted delivery vehicle.

Results: Polymersomes have a smallest average diameter of 145 ± 21 nm and encapsulate β-galactosidase at 72.0 ± 12.2% efficiency. PEGPLA polymersomes demonstrate limited release at physiologic pH (7.4), with a burst release at the acidic pH (4.8) of the lysosome. PEGPLA polymersomes facilitate delivery of active β-galactosidase to an in vitro model of GM1 gangliosidosis.

Conclusion: The foundation has been laid for testing of PEGPLA polymersomes to deliver enzymatic treatments to the brain in lysosomal storage disorders for the first time.

Keywords: GM1 gangliosidosis; blood–brain barrier delivery; enzyme replacement therapy; nanomedicine; polymersomes.

MeSH terms

Brain / metabolism
Cell Line
Drug Carriers / chemistry*
Drug Liberation
Enzyme Replacement Therapy / methods*
Gangliosidosis, GM1 / drug therapy
Humans
Hydrogen-Ion Concentration
Lactates / chemistry*
Nanoparticles / chemistry
Particle Size
Permeability
Polyethylene Glycols / chemistry*
Surface Properties
beta-Galactosidase / pharmacology*

Substances

Drug Carriers
Lactates
poly(lactic acid-ethylene glycol)
Polyethylene Glycols
beta-Galactosidase