Oral Apomorphine Delivery from Solid Lipid Nanoparticles with Different Monostearate Emulsifiers: Pharmacokinetic and Behavioral Evaluations
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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Sustained delivery and higher bioavailability of ropirinole, bromocriptine and apomorphine could be achieved through SLNs.
“Sustained delivery and higher bioavailability of ropirinole, bromocriptine and apomorphine could be achieved through SLNs.126,127”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [127]
Cites
Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art
Müller, R. (2000) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(00)00087-4 · Cited by 3,759 · see citing works
Effect of pegylation on pharmaceuticals
Harris, J. M., & Chess, R. B. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1033 · Cited by 3,431 · see citing works
Nanoparticulate systems for brain delivery of drugs.
Kreuter, J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00122-8 · Cited by 1,107 · see citing works
Nanoparticulate systems for brain delivery of drugs
Kreuter, J. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.015 · Cited by 958 · see citing works
Solid lipid nanoparticles (SLN) for controlled drug delivery – Drug release and release mechanism
Mühlen, A. Z., Schwarz, C., & Mehnert, W. (1998) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(97)00150-1 · Cited by 945 · see citing works
Schwarting, R. K. W., & Huston, J. P. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00040-8 · Cited by 741 · see citing works
Potential of solid lipid nanoparticles in brain targeting.
Kaur, I. P., Bhandari, R., Bhandari, S., & Kakkar, V. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.12.018 · Cited by 615 · see citing works
Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles
Venkateswarlu, V., & Manjunath, K. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.01.005 · Cited by 558 · see citing works
Fang, J., Fang, C.-L., Liu, C.-H., & Su, Y.-H. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.05.008 · Cited by 518 · see citing works
Self-citationFreitas, C., & Müller, R. H. (1999) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(98)00074-5 · Cited by 484 · see citing works
Long-circulating pegylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery.
Calvo, P., Gouritin, B., Chacun, H., Desmaële, D., D'Angelo, J., Noel, J.-P., Georgin, D., Fattal, E., Andreux, J. P., & Couvreur, P. (2001) · Pharmaceutical Research · doi:10.1023/a:1010931127745 · Cited by 443 · see citing works
Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN)
Helgason, T., Awad, T. S., Kristbergsson, K., McClements, D. J., & Weiss, J. (2009) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2009.03.012 · Cited by 341 · see citing works
Body Distribution of Camptothecin Solid Lipid Nanoparticles After Oral Administration
Yang, S., Zhu, J., Yu, L., Liang, B., & Yang, C. (1999) · Pharmaceutical Research · doi:10.1023/a:1018888927852 · Cited by 324 · see citing works
Oral bioavailability of cyclosporine: Solid lipid nanoparticles (SLN®) versus drug nanocrystals
Müller, R. H., Runge, S., Ravelli, V., Mehnert, W., Thünemann, A. F., & Souto, E. B. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.02.045 · Cited by 304 · see citing works
Paliwal, R., Paliwal, S. R., Vaidya, B., Khatri, K., Goyal, A. K., Mishra, N., Mehta, A., & Vyas, S. P. (2008) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2008.08.003 · Cited by 288 · see citing works
Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin
Zhang, N., Ping, Q. N., Huang, G., Xu, W., Cheng, Y., & Han, X. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.07.026 · Cited by 286 · see citing works
Yuan, H., Wang, L., Du, Y., You, J., Hu, F., & Zeng, S. (2007) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2007.06.011 · Cited by 216 · see citing works
Stability of lipid excipients in solid lipid nanoparticles☆
Radomska-Soukharev, A. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.04.004 · Cited by 206 · see citing works
Müller, R. H. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2007.07.006 · Cited by 199 · see citing works
García-Fuentes, M., Prego, C., Torres, D., & Alonso, M. J. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.02.008 · Cited by 171 · see citing works
Recovery of erectile function by the oral administration of apomorphine
Heaton, J. P. W., Morales, Á., ADAMS, M. A., Johnston, B., & El‐Rashidy, R. (1995) · Urology · doi:10.1016/0090-4295(95)80005-0 · Cited by 170 · see citing works
Recent Advances and Patents on Solid Lipid Nanoparticles
Sawant, K. K., & Dodiya, S. (2008) · Recent Patents on Drug Delivery & Formulation · doi:10.2174/187221108784534081 · Cited by 153 · see citing works
Solid Lipid Nanoparticles in Lymph and Plasma After Duodenal Administration to Rats
Bargoni, A., Cavalli, R., Caputo, O., Fundaro', A., Gasco, M. R., & Zara, G. P. (1998) · Pharmaceutical Research · doi:10.1023/a:1011975120776 · Cited by 148 · see citing works
Zara, G. P., Bargoni, A., Cavalli, R., Fundaro', A., Vighetto, D., & Gasco, M. R. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10129 · Cited by 143 · see citing works
Triglyceride-Based Microemulsion for Intravenous Administration of Sparingly Soluble Substances
von Corswant, C., Thorén, P., & Engström, S. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js970258w · Cited by 121 · see citing works
Priano, L., Esposti, D., Esposti, R., Castagna, G., Medici, C. D., FRASCHINI, F., Gasco, M. R., & Mauro, A. (2007) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2007.809 · Cited by 112 · see citing works
Preparation and Characterization of Solid Lipid Nanoparticles Containing Silibinin
Zhang, J. Q., Liu, J., Li, X. L., et al. (2007) · Drug Delivery · doi:10.1080/10717540701203034 · Cited by 99 · see citing works
Olbrich, C., Gessner, A., Schröder, W., et al. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.02.024 · Cited by 94 · see citing works
Wang, J., Liu, K., Sung, K. C., Tsai, C.-Y., & Fang, J. (2009) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2009.06.008 · Cited by 87 · see citing works
Self-citationImprovement of cefpodoxime proxetil oral absorption in rats by an oil-in-water submicron emulsion
Nicolaos, G. (2003) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(03)00365-x · Cited by 84 · see citing works
Datla, K. P., Zbarsky, V., Rai, D., Parkar, S., Osakabe, N., Aruoma, O. I., & Dexter, D. T. (2007) · Journal of the American College of Nutrition · doi:10.1080/07315724.2007.10719621 · Cited by 83 · see citing works
Methotrexate Loaded Solid Lipid Nanoparticles (SLN) for Effective Treatment of Carcinoma
Kandasamy, R., Manickam, S., & Ganeshkumar, P. A. (2006) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2006.457 · Cited by 78 · see citing works
Zhang, X., Pan, W., Gan, L., et al. (2008) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.56.1645 · Cited by 75 · see citing works
Intranasal bioavailability of apomorphine from carboxymethylcellulose-based drug delivery systems
Ugwoke, M. I., Kaufmann, G., Verbeke, N., et al. (2000) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(00)00434-8 · Cited by 73 · see citing works
Camp, D. M., Loeffler, D. A., Farrah, D. M., Borneman, J. N., & LeWitt, P. A. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-17 · Cited by 72 · see citing works
A study of the formulation design of acoustically active lipospheres as carriers for drug delivery
Fang, J., Hung, C., Liao, M.-H., & Chien, C.-C. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2007.01.008 · Cited by 70 · see citing works
Self-citationApomorphine in Dopaminergic Therapy
Subramony, J. A. (2006) · Molecular Pharmaceutics · doi:10.1021/mp060012c · Cited by 65 · see citing works
The pharmacology and clinical pharmacokinetics of apomorphine SL
Argiolas, A., & Hedlund, H. (2001) · British Journal of Urology · doi:10.1046/j.1464-4096.2001.00124.x · Cited by 49 · see citing works
Apomorphine for the acute treatment of “off” episodes in Parkinson's disease
Stacy, M. A., & Silver, D. E. (2007) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2007.07.016 · Cited by 46 · see citing works
Karuppagounder, S. S., Saravanan, K. S., Chandra, G., et al. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.06.025 · Cited by 44 · see citing works
Kelsey, J. E., Langelier, N. A., Oriel, B. S., & Reedy, C. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1319-0 · Cited by 36 · see citing works
Mode of action of a new oral treatment for erectile dysfunction: apomorphine SL
Rampin, O. (2001) · British Journal of Urology · doi:10.1046/j.1464-4096.2001.00125.x · Cited by 29 · see citing works
Kabuto, H., Amakawa, M., Mankura, M., Yamanushi, T. T., & Mori, A. (2009) · Neurochemical Research · doi:10.1007/s11064-008-9909-0 · Cited by 27 · see citing works
Poullain-Termeau, S., Crauste–Manciet, S., Brossard, D., et al. (2008) · Drug Delivery · doi:10.1080/10717540802321792 · Cited by 21 · see citing works
Danhof, M. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(98)00033-7 · Cited by 19 · see citing works
Vorobyov, V., & Sengpiel, F. (2008) · Experimental Brain Research · doi:10.1007/s00221-008-1519-1 · Cited by 16 · see citing works
[Hypoglycemic effect of polysaccharide-coated insulin liposomes after oral administration in mice].
Wu, Z., Ping, Q. N., Lai, J., et al. (2003) · PubMed · Cited by 11 · see citing works
Abarca, B., Ballesteros, R., Bielsa, P., et al. (2003) · European Journal of Medicinal Chemistry · doi:10.1016/s0223-5234(03)00057-6 · Cited by 8 · see citing works
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Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645 · see citing works
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Satapathy, M. K., Yen, T.-L., Jan, J.-S., Tang, R.-D., Wang, J.-Y., Taliyan, R., & Yang, C.-H. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081183 · Cited by 318 · see citing works
Leyva-Gómez, G., Cortés, H., Magaña, J. J., Leyva-García, N., Quintanar-Guerrero, D., & Florán, B. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.02.009 · Cited by 102 · see citing works
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Nunes, A., Al-Jamal, K. T., & Kostarelos, K. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.026 · Cited by 75 · see citing works
- 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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