Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 17, Issue -, Pages 236-245Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2019.01.014
Keywords
Polycarbonate nanoparticles; Apomorphine delivery; Boronate ester bond; BBB; Base catalyst
Funding
- Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore)
- IBM Almaden Research Center
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Apomorphine (AMP, used for treatment of Parkinson's disease) is susceptible to oxidation. Its oxidized products are toxic. To overcome these issues, AMP was conjugated to phenylboronic acid-functionalized polycarbonate through pH-sensitive covalent boronate ester bond between phenylboronic acid and catechol in AMP. Various conditions (use of base as catalyst, reaction time and initial drug loading) were optimized to achieve high AMP conjugation degree and mitigate polymer degradation caused by amine in AMP. Pyridine accelerated AMP conjugation and yielded similar to 74% conjugation within 5 min. Tertiary amine groups were incorporated to polycarbonate, and served as efficient catalyst (similar to 80% conjugation within 5 min). AMP-conjugated polymer self-assembled into nanoparticles. AMP release from the nanoparticles was minimal at pH 7.4, while in acidic enviromnent (endolysosomes) rapid release was observed. Encapsulation protected AMP from oxidization. The nanoparticles were significantly accumulated in the brain tissue after intranasal delivery. These AMP-loaded nanoparticles have potential use for treatment of Parkinson's disease. (C) 2019 Elsevier Inc. All rights reserved.
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