Cited by 137Drug Solubulity and Delivery SystemsAdvanced Drug Delivery SystemsNanoparticle-Based Drug Delivery

Oral Apomorphine Delivery from Solid Lipid Nanoparticles with Different Monostearate Emulsifiers: Pharmacokinetic and Behavioral Evaluations

Tsai, Ming-Jun, Huang, Yaw-Bin, Wu, Pao-Chu, Fu, Yaw-Syan, Kao, Yao-Ren, Fang, Jia-You, Tsai, Yi-Hung·2011·Journal of Pharmaceutical Sciences

Abstract

Apomorphine, a dopamine receptor agonist for treating Parkinson's disease, has very poor oral bioavailability (<2%) due to the first-pass effect. The aim of this work was to investigate whether the oral bioavailability and brain regional distribution of apomorphine could be improved by utilizing solid lipid nanoparticles (SLNs). Glyceryl monostearate (GMS) and polyethylene glycol monostearate (PMS) were individually incorporated into SLNs as emulsifiers. It was found that variations in the emulsifiers had profound effects on the physicochemical characteristics. Mean diameters of the GMS and PMS systems were 155 and 63 nm, respectively. More than 90% of the apomorphine was entrapped in the SLNs. The interfacial film was the likely location for most of apomorphine molecules. The PMS system, when incubated in simulated intestinal medium, was found to be more stable in terms of particle size and encapsulation efficiency than the GMS system. Using the GMS and PMS systems to orally administer apomorphine (26 mg/kg) equally enhanced the bioavailability in rats. SLNs showed 12- to 13-fold higher bioavailability than the reference solution. The drug distribution in the striatum, the predominant site of therapeutic action, also increased when using the SLNs. The anti-Parkinsonian activity of apomorphine was evaluated in rats with 6-hydroxydopamine-induced lesions, a model of Parkinson's disease. The contralateral rotation behavior was examined after oral apomorphine delivery. The total number of rotations increased from 20 to 94 and from 20 to 115 when the drug was administered from SLNs containing GMS and PMS, respectively. The experimental results suggest that SLNs may offer a promising strategy for apomorphine delivery via oral ingestion.

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Crossref · 10.1002/jps.22285

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Authors
Tsai, M.-J., Huang, Y.-B., Wu, P.-C., Fu, Y.-S., Kao, Y.-R., Fang, J.-Y., & Tsai, Y.-H.
Affiliations
  • Department of Health (TW)
  • Kaohsiung Medical University (TW)
  • Chang Gung University (TW)
Corresponding author
  • Fang, Jia-You
  • Tsai, Yi-Hung
Venue
Journal of Pharmaceutical Sciences
Publisher
Elsevier BV
Published
2011-02
Volume
100
Issue
2
Pages
547-557
ISSN
0022-3549 (ISSN-L)
OpenAlex
W2013567835
Cited by
137
References
48
Citations by year
2026: 1 · 2025: 5 · 2024: 13 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 8 · 2013: 7 · 2012: 8
FWCI
4.24
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmaceutical Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
apomorphine, solid lipid nanoparticles, oral bioavailability, Parkinson's disease, dopamine agonists, glyceryl monostearate, emulsifiers, brain regional distribution, striatum, antiparkinsonian activity, first-pass metabolism, drug delivery
MeSH terms
Administration, Oral, Animals, Antiparkinson Agents, Apomorphine, Behavior, Animal, Brain, Glycerides, Male, Parkinson Disease, Polyethylene Glycols, Rats, Wistar, Emulsifying Agents, Rats, Nanoparticles

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