Abstract
Aim:
To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123.
Methods:
The polymeric micelles of paclitaxel with Pluronic P123 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control.
Results:
By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic P123 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37°C. In the pharmacokinetic assessment, t½β and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study.
Conclusion:
Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.
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References
Rowinsky EK, Donehower RC . Paclitaxel (Taxol). N Engl J Med 1995; 332: 1004–14.
Spencer CM, Faulds D . Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. Drugs 1994; 48: 794–847.
Onetto N, Canett R, Winograd B, Catane R, Dougan M, Grechko J, et al. Overview of taxol safety. J Natl Cancer Inst Monogr 1993; 15: 131–9.
Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, et al. Hypersensitivity reactions from taxol. J Clin Oncol 1990; 8: 1263–8.
Dorr RT . Pharmacology and toxicology of Cremophor EL diluent. Ann Pharmacother 1994; 28 ( 5 Suppl): S11–4.
Crosasso P, Ceruti M, Brusa P, Arpicco S, Dosio F, Cattel L . Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes. J Control Release 2000; 63: 19–30.
Lundberg BB, Risovic V, Ramaswamy M, Wasan KM . A lipophilic paclitaxel derivative incorporated in a lipid emulsion for parenteral administration. J Control Release 2003; 86: 93–100.
Alkan-Onyuksel H, Ramakrishnan S, Chai HB, Pezzuto JM . A mixed micellar formulation suitable for the parenteral administration of taxol. Pharm Res 1994; 11: 206–12.
Liu Y, Chen GS, Chen Y, Cao DX, Ge ZQ, Yuan YJ . Inclusion complexes of paclitaxel and oligo(ethylenediamino) bridged bis (beta-cyclodextrin)s: solubilization and antitumor activity. Bioorg Med Chem 2004; 12: 5767–75.
Rodrigues P, Scheuermann K, Stockmar C, Maier G, Fiebig H, Unger C, et al. Synthesis and in vitro efficacy of acid-sensitive poly(ethylene glycol) paclitaxel conjugates. Bioorg Med Chem Lett 2003; 13: 355–60.
Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y . Block copolymer micelles as vehicles for drug delivery. J Control Release 1993; 24: 119–32.
Kataoka K, Harada A, Nagasaki Y . Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Del Rev 2001; 47: 113–31.
Kabanov A, Batrakova E, Alakhov V . Pluronic block copolymers for overcoming drug resistance in cancer. Adv Drug Del Rev 2002; 54: 759–79.
Kabanov A, Batrakova E, Miller DW . Pluronic block copolymers as modulators of drug efflux transporter activity in the blood-brain barrier. Adv Drug Del Rev 2003; 55: 151–64.
Croy SR, Kwon GS . The effects of Pluronic block copolymers on the aggregation state of nystatin. J Control Release 2004; 95: 161–71.
Kabanov A, Batrakova E, Alakhov V . Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 2002; 82: 189–212.
Kim SC, Kim DW, Shim YH, Bang JS, Oh HS, Kim SW, et al. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release 2001; 72: 191–202.
Zhang X, Jackson J, Burt H . Development of amphiphilic diblock copolymers as micellar carriers of taxol. Int J Pharm 1996; 132: 195–206.
Cho YW, Lee J, Lee SC, Huh KM, Park K . Hydrotropic agents for study of in vitro paclitaxel release from polymeric micelles. J Control Release 2004; 97: 249–57.
Huh KM, Lee SC, Cho YW, Lee J, Jeong JH, Park K . Hydrotropic polymer micelle system for delivery of paclitaxel. J Control Release 2005; 101: 59–68.
Grindel JM, Jaworski T, Piraner O, Emanuele RM, Balasubramanian M . Distribution, metabolism, and excretion of a novel surface-active agent, purified poloxamer 188, in rats, dogs, and humans. J Pharm Sci 2002; 91: 1936–47.
Batrakova EV, Li S, Li Y, Alakhov VY, Elmquist WF, Kabanov AV . Distribution kinetics of a micelle-forming block copolymer Pluronic P85. J Control Release 2004; 100: 389–97.
Gao Z, Fain HD, Rapoport N . Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers. Molecular Pharmaceutics 2004; 1: 317–30.
Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC . Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 1993; 20 ( 4 suppl 3): 1–15.
Rowinsky EK, Donehower RC . The clinical pharmacology of paclitaxel (Taxol). Semin Oncol 1993; 20 ( Suppl 2): 16–25.
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Project supported by the National Natural Science Foundation of China (No 30472094).
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Han, Lm., Guo, J., Zhang, Lj. et al. Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123. Acta Pharmacol Sin 27, 747–753 (2006). https://doi.org/10.1111/j.1745-7254.2006.00340.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00340.x
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