Preparation and characterization of thermally responsive block copolymer micelles comprising poly(N-isopropylacrylamide-b-DL-lactide)
Abstract
The thermally sensitive block copolymer, poly(N-isopropylacrylamide-b-dl-lactide) (PIPAAm-PLA), was synthesized by ring-opening polymerization of dl-lactide initiated from hydroxy-terminated poly (N-isopropylacrylamide) (PIPAAm). A PIPAAm bearing a single terminal hydroxyl group was prepared by telomerization using 2-hydroxyethanethiol as a chain-transfer agent. Successful preparation of PIPAAm and the PIPAAm-PLA block copolymer was verified by gel permeation chromatography (GPC) and 1H-NMR spectroscopy. Polymeric micelles were prepared from block copolymers using a dialysis method. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. Dynamic light scattering measurements were used to observe the formation of micellar structures approximately 40 nm in diameter, which do not change between 20 degreesC and 30 degreesC. Above the LCST, polymer micelles aggregated, a phenomenon found to be reversible since the aggregates dissociated again by cooling below the LCST. Further observations using atomic force microscopy (AFM) confirmed this behaviour. The properties of this block copolymer system are interesting from both applied and fundamental perspectives, particularly for active targeting as drug carriers.
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Solution Properties of Poly(N-isopropylacrylamide)
Heskins, M., & Guillet, J. E. (1968) · Journal of Macromolecular Science Part A - Chemistry · doi:10.1080/10601326808051910 · Cited by 3,121 · see citing works
Biodegradable block copolymers as injectable drug-delivery systems
Jeong, B., Bae, Y. H., Lee, D. S., & Kim, S. W. (1997) · Nature · doi:10.1038/42218 · Cited by 1,999 · see citing works
Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study
Wilhelm, M., Zhao, C. L., Wang, Y., Xu, R., Winnik, M. A., Mura, J.-L., Riess, G., & Croucher, M. D. (1991) · Macromolecules · doi:10.1021/ma00005a010 · Cited by 1,276 · see citing works
Okano, T., Yamada, N., Sakai, H., & Sakurai, Y. (1993) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820271005 · Cited by 1,021 · see citing works
Self-citationThermo‐responsive polymeric surfaces; control of attachment and detachment of cultured cells
Yamada, N., Okano, T., Sakai, H., et al. (1990) · Die Makromolekulare Chemie Rapid Communications · doi:10.1002/marc.1990.030111109 · Cited by 984 · see citing works
Self-citationThe Py scale of solvent polarities
Dong, D. C., & Winnik, M. A. (1984) · Canadian Journal of Chemistry · doi:10.1139/v84-437 · Cited by 696 · see citing works
Block and graft copolymer micelles in solution
Tuzar, Z., & Kratochvı́l, P. (1976) · Advances in Colloid and Interface Science · doi:10.1016/0001-8686(76)80009-7 · Cited by 442 · see citing works
Cammas‐Marion, S., Suzuki, K., Sone, C., Sakurai, Y., Kataoka, K., & Okano, T. (1997) · Journal of Controlled Release · doi:10.1016/s0168-3659(97)00040-0 · Cited by 355 · see citing works
Self-citationFluorescence probe techniques used to study micelle formation in water-soluble block copolymers
Zhao, C. L., Winnik, M. A., Riess, G., & Croucher, M. D. (1990) · Langmuir · doi:10.1021/la00092a038 · Cited by 326 · see citing works
Polymer conjugates with anticancer activity
Putnam, D. A., & Kopec̆ek, J. (1995) · Advances in polymer science · doi:10.1007/3540587888_14 · Cited by 317 · see citing works
Masayuki, Y., Miyauchi, M., Yamada, N., Teruo, O., Sakurai, Y., Kataoka, K., & Inoue, S. (1990) · Journal of Controlled Release · doi:10.1016/0168-3659(90)90139-k · Cited by 290 · see citing works
Self-citationTemperature-responsive bioconjugates. 2. Molecular design for temperature-modulated bioseparations
Takei, Y. G., Aoki, T., Sanui, K., Ogata, N., Okano, T., & Sakurai, Y. (1993) · Bioconjugate Chemistry · doi:10.1021/bc00023a006 · Cited by 214 · see citing works
Self-citationNanoparticle-based dmg delivery systems
Kreuter, J. (1991) · Journal of Controlled Release · doi:10.1016/0168-3659(91)90040-k · Cited by 205 · see citing works
Tardi, P. G., Boman, N. L., & Cullis, P. R. (1996) · Journal of drug targeting · doi:10.3109/10611869609015970 · Cited by 184 · see citing works
Biodistribution of Micelle-Forming Polymer–Drug Conjugates
Kwon, G. S., Yokoyama, M., Okano, T., Sakurai, Y., & Kataoka, K. (1993) · Pharmaceutical Research · doi:10.1023/a:1018998203127 · Cited by 180 · see citing works
Self-citationOgawa, Y., Okada, H., YAMAMOTO, Y., & Shimamoto, T. (1988) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.36.2576 · Cited by 171 · see citing works
Chung, J. E., Yokoyama, M., Suzuki, K., Aoyagi, T., Sakurai, Y., & Okano, T. (1997) · Colloids and Surfaces B Biointerfaces · doi:10.1016/s0927-7765(97)00015-5 · Cited by 169 · see citing works
Self-citationYang, H. M., & Reisfeld, R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1189 · Cited by 151 · see citing works
(1992) · PubMed · Cited by 140 · see citing works
Takei, Y. G., Aoki, T., Sanui, K., et al. (1993) · Bioconjugate Chemistry · doi:10.1021/bc00019a006 · Cited by 138 · see citing works
Polyalkylcyanoacrylate nanoparticles as drug carrier: present state and perspectives
Couvreur, P., & Vauthier, C. (1991) · Journal of Controlled Release · doi:10.1016/0168-3659(91)90058-l · Cited by 113 · see citing works
Okano, T., Kikuchi, A., Sakurai, Y., Takei, Y., & Ogata, N. (1995) · Journal of Controlled Release · doi:10.1016/0168-3659(95)00054-c · Cited by 105 · see citing works
Self-citationOkano, T., Katayama, M., & Shinohara, I. (1978) · Journal of Applied Polymer Science · doi:10.1002/app.1978.070220206 · Cited by 96 · see citing works
Self-citationTargetable drug carriers: present status and a future perspective
Yokoyama, M., & Okano, T. (1996) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00439-5 · Cited by 72 · see citing works
Self-citationThédrez, P., Saccavini, J. C., Nolibe, D., et al. (1989) · PubMed · Cited by 32 · see citing works
Temperature–Responsive Bioconjugates
Takei, Y. G., Aoki, T., Sanui, K., et al. (1994) · Elsevier eBooks · doi:10.1016/b978-1-4832-8380-7.50014-6 · Cited by 21 · see citing works
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Micellar Nanocarriers: Pharmaceutical Perspectives
Torchilin, V. P. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9132-0 · Cited by 1,910 · see citing works
Biodegradable synthetic polymers: Preparation, functionalization and biomedical application
Tian, H., Tang, Z., Zhuang, X., Chen, X., & Jing, X. (2012) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2011.06.004 · Cited by 1,293 · see citing works
Polymeric micelles—A new generation of colloidal drug carriers
Jones, M.-C., & Leroux, J.-C. (1999) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(99)00039-9 · Cited by 1,256 · see citing works
Ghezzi, M., Pescina, S., Padula, C., Santi, P., Del Favero, E., Cantù, L., & Nicoli, S. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.02.031 · Cited by 1,135 · see citing works
Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery
Rapoport, N. (2007) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.05.009 · Cited by 1,002 · see citing works
Thermo-sensitive polymeric micelles based on poly (N-isopropylacrylamide) as drug carriers
Wei, H., Cheng, S.-X., Zhang, X.-Z., & Zhuo, R.-X. (2009) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2009.05.002 · Cited by 718 · see citing works
Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs
Lu, Y., & Park, K. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.08.042 · Cited by 572 · see citing works
Functionalized micellar systems for cancer targeted drug delivery
Sutton, D., Nasongkla, N., Blanco, E., & Gao, J. (2007) · Pharmaceutical Research · doi:10.1007/s11095-006-9223-y · Cited by 557 · see citing works
Thermo and pH Dual‐Responsive Nanoparticles for Anti‐Cancer Drug Delivery
Zhang, L., Guo, R., Yang, M., Jiang, X., & Liu, B. (2007) · Advanced Materials · doi:10.1002/adma.200601817 · Cited by 269 · see citing works
Polymeric micelles: authoritative aspects for drug delivery
Kulthe, S. S., Choudhari, Y. M., Inamdar, N. N., & Mourya, V. (2012) · Designed Monomers and Polymers · doi:10.1080/1385772x.2012.688328 · Cited by 235 · see citing works
You, Y., Hong, C., Wang, W., Lu, W., & Pan, C. (2004) · Macromolecules · doi:10.1021/ma048444t · Cited by 151 · see citing works
Drug releasing nanoplatforms activated by alternating magnetic fields
Mertz, D., Sandre, O., & Bégin-Colin, S. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.02.025 · Cited by 119 · see citing works
Liu, S. Q., Tong, Y. W., & Yang, Y. Y. (2005) · Molecular BioSystems · doi:10.1039/b501756b · Cited by 74 · see citing works
Zhang, W., Wang, S., Li, X., Yuan, J., & Wang, S. (2012) · European Polymer Journal · doi:10.1016/j.eurpolymj.2012.01.019 · Cited by 38 · see citing works
Wang, X., Li, S., Wan, Z., Quan, Z., & Tan, Q. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.12.046 · Cited by 38 · see citing works
- Authors
- Kohori, F., Sakai, K., Aoyagi, T., Yokoyama, M., Sakurai, Y., & Okano, T.
- Affiliations
- Waseda University (JP)
- Tokyo Women's Medical University (JP)
- Corresponding author
- Okano, Teruo
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 55
- Issue
- 1
- Pages
- 87-98
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2031773818
- Cited by
- 273
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 12 · 2016: 4 · 2015: 7 · 2014: 12 · 2013: 12 · 2012: 12
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (08672569)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- poly(N-isopropylacrylamide), poly(D,L-lactide), block copolymer micelles, lower critical solution temperature, micellar aggregation, drug carriers, active targeting, ring-opening polymerization, telomerization
- MeSH terms
- Acrylamides, Chromatography, Gel, Light, Micelles, Magnetic Resonance Spectroscopy, Scattering, Radiation, Spectrometry, Fluorescence, Temperature, Microscopy, Atomic Force
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