Jessica M Kelly1,2,3, Amanda L Gross2,4, Douglas R Martin2,3,4, Mark E Byrne1,3,5. 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.
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.
AIM: Polymersomes are created to deliver an enzyme-based therapy to the brain in lysosomal storage diseasepatients. 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 GM1gangliosidosis. 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.
Authors: Meihua Luo; Leo Kit Cheung Lee; Bo Peng; Chung Hang Jonathan Choi; Wing Yin Tong; Nicolas H Voelcker Journal: Adv Sci (Weinh) Date: 2022-07-18 Impact factor: 17.521