Thermosensitive Micelles from PEG-Based Ether-anhydride Triblock Copolymers
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The thermosensitive micelles based on the poly(PEG:CPP:SA) terpolymer composed of poly(ethylene glycol) (PEG), 1,3-bis(carboxyphenoxy) propane (CPP) and sebacic acid (SA) were fabricated for application as a promising drug carrier.
The terpolymer can self-assemble into micelles in water by a precipitation technology. The sol–gel transition behaviors were investigated by the tube-tilting method and dynamic rheology. The drug release behaviors were investigated in phosphate-buffered solution (PBS) at 25, 37 and 45°C, respectively, and the tumor cell growth inhibition assays were also evaluated.
The diameters of these micelles increased as the environmental temperature, and the length of CPP and SA chains increased. The micelles with a low concentration underwent sol-to-nanogel transition as temperature increased from the room temperature to the body temperature, while the polymer solutions with a high concentration underwent sol-to-gel transition as the temperature increased from 20 to 70°C. In vitro release profiles consisted of a burst release followed a sustained release. The cytotoxicity results showed that the terpolymer micelles were biocompatible, and the encapsulated doxorubicin. HCl maintained its potent anti-tumor effect.
These micelles may bring the ether-anhydride family of polymers great potential as a novel carrier in nanomedicine.
- Basarkar A, Singh J. Poly (lactide-co-glycolide)-polymethacrylate micellles for intramuscular delivery of plasmid encoding interleukin-10 to prevent autoimmune diabetes in mice. Pharm Res. 2009;26:72–81. CrossRef
- Allen TM, Cullis PR. Drug delivery systems: entering the main stream. Science 2004;303:1818–22. CrossRef
- Hu XL, Liu S, Chen XS. Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: synthesis and characterization. Biomacromolecules 2008;9:553–60. CrossRef
- Kataoka K, Kwon GS, Yokoyama M, Okano T, Sakurai Y. Block copolymer micelles as vehicles for drug delivery. J Control Release. 2006;24:119–32.
- Branco MC, Schneider JP. Review:Self-assembling materials for therapeutic delivery. Acta Biomaterialia. 2009;5:817–31. CrossRef
- Cai SS, Vijayan KS, Cheng D, Lima EM, Discher DE. Micelles of different morphologies—advantages of worm-like filomicelles of PEO-PCL in paclitaxel delivery. Pharm Res. 2007;24:2099–109. CrossRef
- Martini L, Attwood D, Collett J. The bioadhesive properties of a triblock copolymer of ε-caprolactone and ethylene oxide. Int J Pharm. 2005;113:223–9. CrossRef
- Cohn D, Salomon AH. Biodegradable multiblock PEO/PLA thermoplastic elastomers:molecular design and properties. Polymer 2005;46:2068–75. CrossRef
- Lavasanifar A, Samue J, Kwon GS. Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery. Adv Drug Deliv Rev. 2005;54:169–90. CrossRef
- Rapoport N. Combined cancer therapy by micellar-encapsulated drug and ultrasound, nanotechnology for cancer therapy. Boca Raton. 2006;2:417–37.
- Vakil R, Kwo GS. Poly(ethyleneglycol)-b-poly(ε-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media. Langmuir 2006;22:9723–9. CrossRef
- Jeong B, Bae YH, Kim SW. Thermoreversible gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions. Macromolecules 2001;32:7064–9. CrossRef
- Joo MK, Sohn YS, Jeong B. Stereoisomeric effect on reverse thermal gelation of poly(ethylene glycol)/poly(lactide)multiblock copolymer. Macromolecules 2007;40:5111–5. CrossRef
- Yang L, Xian ZZ, Wei J, Suming L. Micelles formed by self-assembling of polylactide/poly(ethylene glycol) block copolymers in aqueous solutions. J Colloid Interface Sci. 2007;31:4470–7.
- Wang YP, Xu HP, Zhang X. Tuning the amphiphilicity of building blocks: controlled self-assembly and disassembly for functional supramolecular materials. Adv Mater. 2009;21:2849–64. CrossRef
- Bae Y, Fukushima S, Harada A, Kataoka K. Design of environment-sensitives upramolecular as semblies for intra cellular drug delivery: polymeric micelles that are responsive to intracellular pH change. Angew Chem Int Ed Engl. 2003;42:4640–3. CrossRef
- Webber GB, Wanless EJ, Armes SP, Tang YQ, Li YT, Biggs S. Nano-anemones:stimulus-responsive copolymer-micelle surfaces. Adv Mater. 2004;16:1794–8. CrossRef
- Dong Y, Feng SS. Methoxypoly (ethyleneglycol)-poly(lactide)(MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials 2004;25:2843–9. CrossRef
- Chen G, Hoffman AS. Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 1995;373:49(R)–52.
- Liu TY, Hu SH, Liu DM, Chen SY, Chen IW. Review: biomedical nanoparticle carriers with combined thermal and magnetic responses. Nano Today. 2009;4:52–65. CrossRef
- Hoffman AS. Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics. J Control Release. 1987;6:297–305. CrossRef
- Peppas NA, Bures P. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2005;50:27–46. CrossRef
- Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;43:3–12. CrossRef
- Farhood N, Mohammad N. Biodegradable micelles/polymersomes from fumaric/sebacic acids and poly(ethylene glycol). Biomaterials 2006;24:1175–82.
- Cohn D, Lando G, Sosnik A, Garty S, Levi A. PEO-PPO-PEO based poly(ether ester urethane)s as degradable thermo-responsive multiblock copolymers. Biomaterials 2006;27:1718–27. CrossRef
- Jeong B, Bae YH, Lee DS, Kim SW. Biodegradable block copolymers as injectable drug-delivery systems. Nature 1997;388:860–2. CrossRef
- Zana R, Binanalimb W, Kamenka N. Ethyl(hydroxyethyl) cellulose cationic surfactant interactions-electricalconductivity, self-diffusion, and time-resolved fluorescence, quenching investigations. J Phys Chem. 2007;96:5461–5. CrossRef
- Kamenka N, Burgaud L, Zana R. Electricalconductivity, self-diffusion, and fluorescence probe investigations of the interaction between sodium dodecyl-sulfate and ethyl(hydroxyethyl) cellulose. J Phys Chem. 2004;98:6785–9. CrossRef
- Kim IS, Lee SK, Park YM, Lee YB, Shin SC, Lee KC et al. Physicochemical characterization of poly(L-lactic acid) and poly(D, L-lactide-co-glycolide) nanoparticles with polyethylenimine as gene delivery carrier. Int J Pharm. 2005;298:255–62. CrossRef
- Karnik R, Gu F, Basto P. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett. 2008;8:2906–12. CrossRef
- Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev. 2004;47:113–31. CrossRef
- Fiegel J, Fu J, Hanes J. Synthesis and characterization of PEG-based ether-anhydride terpolymers: novel polymers for controlled drug delivery. Macromolecules 2004;37:7174–80. CrossRef
- Zhang N, Guo SR. Synthesis and micellization of amphiphilic poly(sebacic anhydride)-poly(ethylene glycol)-poly(sebacic anhydride) block copolymers. J Polym Sci Part: A. 2006;44:1271–8. CrossRef
- Lee JS, Joo MK, Oh HJ. Injectable gel: poly(ethylene glycol)-sebacic acid polyester. Polymer 2006;47:3760–6. CrossRef
- Rosen HB, Chang J, Wnek GE, Linhardt RJ, Langer R. Bioerodible polyanhydrides for controlled drug delivery. Biomaterials 1983;4:131–3. CrossRef
- Zhao C, Wang Y, Winnik MA, Riess G, Croucher MD. Fluorescenceprobe technique used to study micelle formation in water-soluble block co-polymer. Langmuir 1999;6:514–6. CrossRef
- Forrest M, Won CY, Malick A, Kwon G. In vitro release of poly(ethylene glycol)-b-poly(ε-caprolactone)micelle. J Control Release. 2006;110:370–7. CrossRef
- Fiegel J, Fu J, Hanes J. Poly(ether-anhydride) dry powder aerosols for sustained drug delivery in the lungs. J Control Release. 2004;96:411–23. CrossRef
- Liu Y, Zhao ZX, Wei J. Micelles formed by self-assembling of polylactide/poly(ethylene glycol) block copolymers in aqueous solutions. J Colloid Interface Sci. 2007;314:470–7. CrossRef
- Adams M, Lavasanifar A, Kwon G. Amphiphilic block copolymers for drug delivery. J Pharm Sci. 2005;92:1343–55. CrossRef
- Kabanov A, Alakhov V. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit Rev Ther Drug. 2007;19:1–72. CrossRef
- Zhang L, Eisenberg A. Multiple morphologies of crew-cut aggregates of polystyrene-b-poly(acrylicacid)block copolymers. Science 1995;268:1728–31. CrossRef
- Cabra H, Nakanishi M, Kumagai M, Jang WD, Nishiyama N, Kataoka K. A photo-activated targeting chemotherapy using glutathione sensitive camptothecin-loaded polymeric micelles. Pharm Res. 2007;24:2099–109. CrossRef
- Rapoport N. Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci. 2007;32:962–90. CrossRef
- Oh KT, Bronich TK, Kabanov AV. Micellar formulationsfor drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers. J Control Release. 2004;94:411–22. CrossRef
- Zhe J, Sun X, Moon H, Soo Y. Thermosensitive micelles from PEGylated oligopeptides. Polymer 2007;48:3673–8. CrossRef
- Yan H, Yong HY, Zhou F. Synthesis and supramolecular self-assembly of thermosensitive amphiphilic star copolymers based on a hyperbranched polyethe, core. J Polym Sci Part: A. 2008;46:668–81.
- Fraylich F, Wang WX, Sheff KS, Alexander C, Saunders B. Poly(D,L-lactide-co-glycolide) dispersions containing pluronics: from particle preparation to temperature-triggered aggregation. Langmuir 2008;24:7761–8. CrossRef
- Tang Y, Singh J. Biodegradable and biocompatible thermosensitive polymer based injectable implant for controlled release of protein. Int J Pharm. 2009;365:34–43. CrossRef
- Gong Y, Shi S, Wu L, Gou ML, Yin QQ, Guo QF et al. Biodegradable in situ gel-forming controlled drug delivery systembased on thermosensitive PCL–PEG–PCL hydrogel. Part 2: sol–gel–sol transition and drug delivery behavior. Acta Biomater. 2009;5:3358–70. CrossRef
- Nagahama KJ, Imai YC, Nakayama T, Ohmura J, Ouchi T, Ohya Y. Thermo-sensitive sol–gel transition of poly(depsipeptideco-lactide)-g-PEG copolymers in aqueous solution. Polymer 2009;23:1–9.
- Yu L, Chang GT, Zhang H, Ding JD. Temperature-induced spontaneous sol–gel transitions of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) triblock copolymers and their end-capped derivatives in water. J Polym Sci Part: A. 2007;45:1122–33. CrossRef
- Mata JP, Majhi PR, Guo C, Liu HZ, Bahadur P. Concentration, temperature, and salt-induced micellization of a triblock copolymer Pluronic L64 in aqueous media. J Colloid Interface Sci. 2005;292:548–56. CrossRef
- Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In situ forming parenteral drug delivery systems: an overview. Euro J Pharm Biopharm. 2004;58:445–55. CrossRef
- Lasic DD. Doxorubicin in sterically stabilized liposomes. Nature 1996;380:561–2. CrossRef
- Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7tumor. J Control Release. 2005;103:405–18. CrossRef
- Yoo HS, Park TG. Folate receptor targeted biodegradable polymeric doxorubicin micelles. J Control Release. 2004;96:273–83. CrossRef
- Thermosensitive Micelles from PEG-Based Ether-anhydride Triblock Copolymers
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