Abstract
Purpose. The aim of this study was to investigate the specific changes in body distribution of camptothecin (CA) through incorporation into solid lipid nanoparticles (SLN) by peroral route.
Methods. Camptothecin loaded solid lipid nanoparticles (CA-SLN) coated with poloxamer 188 were produced by high pressure homogenization. The CA-SLN were characterized by transmission electron microscopy and electrophoretic mobility measurement. In vitro release characteristics of camptothecin from CA-SLN were studied at different pH media. The concentration of camptothecin in organs was determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after oral administration of CA-SLN and a camptothecin control solution (CA-SOL).
Results. Our results showed that CA-SLN had an average diameter 196.8 nm with Zeta potential of −69.3 mV. The encapsulation efficiency of camptothecin was 99.6%, and in vitro drug release was achieved up to a week. There were two peaks in the camptothecin concentration-time curves in plasma and tested organs after oral administration of CA-SLN. The first peak was the result of free drug and the second peak was indicative of gut uptake of CA-SLN after 3 hours. In tested organs, the area under curve (AUC) and mean residence time (MRT) of CA-SLN increased significantly as compared with CA-SOL, and the increase of brain AUC was the highest among all tested organs.
Conclusions. The results indicate SLN could be a promising sustained release and targeting system for camptothecin or other lipophilic antitumor drugs after oral administration.
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REFERENCES
R. H. Müller, W. Mehnert, J. S. Lucks, C. Schwarz, A. zur Mühlen, H. Weyhers, C. Freitas, and D. Rühl. Solid lipid nanoparticles (SLN)-An alternative colloidal carrier system for controlled drug delivery. Eur. J. Pharm. Biopharm. 41:62-69 (1995).
C. Schwarz, W. Mehnert, J. S. Lucks, and R. H. Müller. Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization. J. Contr. Rel. 30:83-96 (1994).
B. Siekmann, and K. Westesen. Investigations on solid lipid nanoparticles prepared by precipitation in o/w emulsions. Eur. J. Pharm. Biopharm. 43:104-109 (1996).
R. Cavalli, E. Marengo, L. Rodriguez, and M. R. Gasco. Effects of some experimental factors on the production process of solid lipid nanoparticles. Eur. J. Pharm. Biopharm. 43:110-115 (1996).
R. H. Müller, D. Rühl, S. Runge, K. Schulze-Forster, and W. Mehnert. Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant. Pharm. Res. 14:458-462 (1997).
J. Humberstone, and W. N. Charman. Lipid-based vehicles for the oral delivery of poorly water soluble drugs, Adv. Drug Deliv. Rev. 25:103-128 (1997).
E. C. Lavelle, S. Sharf, N. W. Thomas, J. Holland, and S. S. Davis. The importance of gastrointestinal uptake of particles in the design of oral delivery systems. Adv. Drug Deliv. Rev. 18:5-22 (1995).
C. Jaxel, K. W. Kohn, M. C. Wani, M. E. Wall, and Y. Pommier. Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: Evidence for a specific receptor site and for a relation to antitumor activity. Cancer Res. 49:1465-1469 (1989).
M. Potmesil. Camptothecins: from bench research to hospital wards. Cancer Res. 54:1431-1439 (1994).
J.-P. Lon and A. E. Ahmed. Determination of camptothecin in biological fluids using reversed-phase high-performance liquid chromatography with fluorescence detection. J. Chromatogr. Biomed. Appl. 530:367-376 (1990).
J. H. Beijnen. High-performance liquid chromatographic analysis of the antitumour drug camptothecin and its lactone ring-opened form in rat plasma. J. Chromatogr. Biomed. Appl. 617:111-117 (1993).
J. Fassberg and V. J. Stella. A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. J. Pharm. Sci. 81:676-684 (1992).
T. G. Burke and Z. Mi. The structural basis of camptothecin interactions with human serum albumin impact on drug stability. J. Med. Chem. 37: 40-46 (1994).
R. H. Müller, D. Rühl, and S. A. Runge. Biodegradation of solid lipid nanoparticles as a function of lipase incubation time. Int. J. Pharm. 144:115-121 (1996).
R. Löbenberg, L. Araujo, and J. Kreuter. Body distribution of azidothymidine bound to nanoparticles after oral administration. Eur. J. Pharm. Biopharm. 44:127-132 (1997).
C. M. Adeyeye and F. F. Chen. Stereoselective disposition of suspensions of conventional and wax-matrix sustained release ibuprofen microspheres in rats. Pharm. Res. 14:1811-1816 (1997).
P. P. Constantinides, G. Welzel, H. Ellens, P. L. Smith, S. Sturgis, S. H. Yiv, and A. B. Owen. Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption enhancement evaluation. Pharm. Res. 13:210-215 (1996).
P. Speiser. Lipidnanopellets als Trägersystem für Arzneimittel zur peroralen Anwendung. European Patent Application EP 0 167 825 (15.01.86).
M. P. Desai, V. Labhasetwar, G. L. Amidon, and R. J. Levy. Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm. Res. 13:1838-1845 (1996).
J. H. Eldridge, C. J. Hammond, J. A. Meulbroek, J. K. Staas, R. M. Gilley, and T. R. Tice. Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the Peyer's patches. J. Conr. Rel. 11:205-214 (1990).
N. Hussain, P. U. Jani, and A. T. Florence. Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat. Pharm. Res. 14:613-618 (1997).
L. H. McMinn, G. M. Hodges, and K. E. Carr. Gastrointestinal uptake and translocation of microparticles in the streptozotocin-diabetic rat. J. Anat. 189:553-559 (1996).
M. Le Ray, M. Vert, J. C. Gautier, and J. P. Benoit. Fate of [14C]poly (DL-lactide-co-glycolide) nanoparticles after intravenous and oral administration to mice. Int. J. Pharm. 106:201-211 (1994).
P. Jani, W. Halbert, J. Langridge, and A. T. Florence. The uptake and translocation of latex nanoparticles and microparticles after oral administration to rats. J. Pharm. Pharmcol. 41:809-812 (1989).
T. Minagava, K. Sakanaka, S. I. Inaba, Y. Sai. I. Tamai, T. Suwa, and A. Tsuji. Blood-brain-barrier transport of lipid microspheres containing clinprost, a prostaglandin I2 analogue. J. Pharm. Pharmacol. 48:1016-1022 (1996).
J. Kreuter, R. N. Alyautdin, D. A. Kharkevich, and A. A. Ivanov. Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res. 674:171-174 (1995).
Z. Mi and T. G. Burke. Differential interactions of camptothecin lactone and carboxylated forms with human blood components. Biochemistry 33:10325-10336 (1994).
J. Kreuter. Drug targeting with nanoparticles. Eur. J. Drug Metab. Pharmacokinet. 19:253-256 (1994).
P. H. Beck, J. Kreuter, W. E. G. Müller, and W. Schatton. Improved peroral delivery of avarol with polybutylcyanoacrylate nanoparticles. Eur. J. Pharm. Biopharm. 40:134-137 (1994).
Y. I. Kim, L. Fluckiger, M. Hoffman, I. Lartaud-Idjouadiene, J. Atkinson, and P. Maincent. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats. Br. J. Pharmacol. 120:399-404 (1997).
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Yang, S., Zhu, J., Lu, Y. et al. Body Distribution of Camptothecin Solid Lipid Nanoparticles After Oral Administration. Pharm Res 16, 751–757 (1999). https://doi.org/10.1023/A:1018888927852
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DOI: https://doi.org/10.1023/A:1018888927852