Combined strategies of apomorphine diester prodrugs and nanostructured lipid carriers for efficient brain targeting

Kuo Sheng Liu, Chih Jen Wen, Tzu Chen Yen, K. C. Sung, Ming Chuan Ku, Jhi Joung Wang*, Jia You Fang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

30 Scopus citations

Abstract

Our aim is to develop nanostructured lipid carriers (NLCs) for loading the apomorphine diester prodrugs, diacetyl apomorphine (DAA) and diisobutyryl apomorphine (DIA), into the brain. NLCs were prepared using sesame oil/cetyl palmitate as the lipid matrices. Experiments were performed with the objective of evaluating the physicochemical characteristics, drug release, safety and brain-targeting efficacy of the NLCs. The size of regular NLCs (N-NLCs) was 214nm. The addition of Forestall (FE) and polyethylene glycol (PEG) to the NLCs (P-NLCs) increased the particle diameter to 250nm. The zeta potentials of N-NLCs and P-NLCs were respectively shown to be 21 and 48mV. Diester prodrugs were more lipophilic and more chemically stable than the parent apomorphine. The hydrolysis study indicated that the prodrugs underwent bioconversion in plasma and brain extract, with DAA exhibiting faster degradation than DIA. Sustained release was achieved through the synergistic effect of integrating strategies of prodrugs and NLCs, with the longer carbon chain showing the slower release (DIA<DAA). None of the NLCs tested here exhibited a toxicity problem according to the examination of neutrophil lactate dehydrogenase (LDH) release and hemolysis. Results of a bioimaging study in mice showed that P-NLCs largely accumulated in the brain. The distribution duration of the fluorescent dye in the brain region was also prolonged by the nanocarriers.

Original languageEnglish
Article number095103
JournalNanotechnology
Volume23
Issue number9
DOIs
StatePublished - 09 03 2012

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