Skip to main content
Log in

Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

  • Review
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10–100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer–polymer and polymer–cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Aliabadi HM, Elhasi S, Mahmud A, Gulamhusein R, Mahdipoor P, Lavasanifar A (2007) Encapsulation of hydrophobic drugs in polymeric micelles through co-solvent evaporation: the effect of solvent composition on micellar properties and drug loading. Int J Pharm 329:158–165

    Article  Google Scholar 

  • Attia ABE, Ong ZY, Hedrick JL, Lee PP, Ee PLR, Hammond PT, Yang YY (2011) Mixed micelles self-assembled from block copolymers for drug delivery. Curr Opin Colloid Interface Sci 16:182–194

    Article  Google Scholar 

  • Bae Y, Kataoka K (2009) Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers. Adv Drug Deliv Rev 61:768–784

    Article  Google Scholar 

  • Bae YH, Yin H (2008) Stability issues of polymeric micelles. J Control Release 131:2–4

    Article  Google Scholar 

  • Beck KR, Korsmeyer R, Kunz RJ (1984) An overview of the glass transition temperature of synthetic polymers. J Chem Educ 61:668–670

    Article  Google Scholar 

  • Blanco E, Bey EA, Dong Y, Weinberg BD, Sutton DM, Boothman DA, Gao J (2007) β-Lapachone-containing PEG–PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells. J Control Release 122:365–374

    Article  Google Scholar 

  • Bontha S, Kabanov AV, Bronich TK (2006) Polymer micelles with cross-linked ionic cores for delivery of anticancer drugs. J Control Release 114:163–174

    Article  Google Scholar 

  • Breslin S, O’Driscoll L (2013) Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today 18:240–249

    Article  Google Scholar 

  • Cajot S, Lautram N, Passirani C, Jérôme C (2011) Design of reversibly core cross-linked micelles sensitive to reductive environment. J Control Release 152:30–36

    Article  Google Scholar 

  • Cammas S, Matsumoto T, Okano T, Sakurai Y, Kataoka K (1997) Design of functional polymeric micelles as site-specific drug vehicles based on poly (α-hydroxy ethylene oxide-co-β-benzyl l-aspartate) block copolymers. Mater Sci Eng C 4:241–247

    Article  Google Scholar 

  • Cammas-Marion S, Okano T, Kataoka K (1999) Functional and site-specific macromolecular micelles as high potential drug carriers. Colloids Surf B Biointerfaces 16:207–215

    Article  Google Scholar 

  • Chan Y, Wong T, Byrne F, Kavallaris M, Bulmus V (2008) Acid-labile core cross-linked micelles for pH-triggered release of antitumor drugs. Biomacromolecules 9:1826–1836

    Article  Google Scholar 

  • Chang C et al (2011) Thermo-responsive shell cross-linked PMMA-b-P (NIPAAm-co-NAS) micelles for drug delivery. Int J Pharm 420:333–340

    Article  Google Scholar 

  • Chang HP, Chen JY, Zhong PS, Chang YH, Liang M (2012) Synthesis and characterization of a new polymer-drug conjugate with pH-induced activity. Polymer 53:3498–3507

    Article  Google Scholar 

  • Chao D, Zhong Z, Jiang Y, Ru C, Meng F (2012) Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: promises, progress and prospects. Nano Today 7:467–480

    Article  Google Scholar 

  • D’Addio SM et al (2012) Effects of block copolymer properties on nanocarrier protection from in vivo clearance. J Control Release 162:208–217

    Article  Google Scholar 

  • Dawidczyk CM, Kim C, Park JH, Russell LM, Lee KH, Pomper MG, Searson PC (2014) State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines. J Control Release 187:133–144

    Article  Google Scholar 

  • Deng C, Jiang Y, Cheng R, Meng F, Zhong Z (2012) Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: promises, progress and prospects. Nano Today 7:467–480

    Article  Google Scholar 

  • Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, Hammer DA (1999) Polymersomes: tough vesicles made from diblock copolymers. Science 284:1143–1146

    Article  Google Scholar 

  • Dong X, Mumper RJ (2010) Nanomedicinal strategies to treat multidrug-resistant tumors: current progress. Nanomedicine 5:597–615

    Article  Google Scholar 

  • Droste D, Dibenedetto A (1969) The glass transition temperature of filled polymers and its effect on their physical properties. J Appl Polym Sci 13:2149–2168

    Article  Google Scholar 

  • Fan H, Huang J, Li Y, Yu J, Chen J (2010) Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin. Polymer 51:5107–5114

    Article  Google Scholar 

  • Garnier S, Laschewsky A (2006) Non-ionic amphiphilic block copolymers by RAFT-polymerization and their self-organization. Colloid Polym Sci 284:1243–1254

    Article  Google Scholar 

  • Gillies ER, Jonsson TB, Fréchet JMJ (2004) Stimuli-responsive supramolecular assemblies of linear-dendritic copolymers. J Am Chem Soc 126:11936–11943

    Article  Google Scholar 

  • Goto F, Ishihara K, Iwasaki Y, Katayama K, Enomoto R, S-i Yusa (2011) Thermo-responsive behavior of hybrid core cross-linked polymer micelles with biocompatible shells. Polymer 52:2810–2818

    Article  Google Scholar 

  • Gunawan C, Breuer M, Hauer B, Rogers PL, Rosche B (2008) Improved (R)-phenylacetylcarbinol production with Candida utilis pyruvate decarboxylase at decreased organic to aqueous phase volume ratios. Biotechnol Lett 30:281–286

    Article  Google Scholar 

  • Haliloglu T, Bahar I, Erman B, Mattice WL (1996) Mechanisms of the exchange of diblock copolymers between micelles at dynamic equilibrium. Macromolecules 29:4764–4771

    Article  Google Scholar 

  • Hayami Y, Ichikawa H, Someya A, Aratono M, Motomura K (1998) Thermodynamic study on the adsorption and micelle formation of long chain alkyltrimethylammonium chlorides. Colloid Polym Sci 276:595–600

    Article  Google Scholar 

  • Honda S, Yamamoto T, Tezuka Y (2013) Tuneable enhancement of the salt and thermal stability of polymeric micelles by cyclized amphiphiles. Nat Commun 4:143–148

    Article  Google Scholar 

  • Hu X, Li H, Luo S, Liu T, Jiang Y, Liu S (2013) Thiol and pH dual-responsive dynamic covalent shell cross-linked micelles for triggered release of chemotherapeutic drugs. Polym Chem 4:695–706

    Article  Google Scholar 

  • Huang CF, Chang FC (2003) Comparison of hydrogen bonding interaction between PMMA/PMAA blends and PMMA-co-PMAA copolymers. Polymer 44:2965–2974

    Article  Google Scholar 

  • Iwamoto T (2013) Clinical application of drug delivery systems in cancer chemotherapy: review of the efficacy and side effects of approved drugs. Biol Pharm Bull 36:715–718

    Article  Google Scholar 

  • Iyama K, Nose T (1998) Kinetics of micelle formation with change of micelle shape in a dilute solution of diblock copolymers. Macromolecules 31:7356–7364

    Article  Google Scholar 

  • Jeong YI et al (2006) Polyion complex micelles composed of all-trans retinoic acid and poly (ethylene glycol)-grafted-chitosan. J Pharm Sci 95:2348–2360

    Article  Google Scholar 

  • Jette KK, Law D, Schmitt EA, Kwon GS (2004) Preparation and drug loading of poly (ethylene glycol)-block-poly (ε-caprolactone) micelles through the evaporation of a cosolvent azeotrope. Pharm Res 21:1184–1191

    Article  Google Scholar 

  • Jin SK, Ji HY (2009) Preparation of core cross-linked micelles using a photo-cross-linking agent. Polymer 50:2204–2208

    Article  Google Scholar 

  • Junquera E, Tardajos G, Aicart E (1993) Effect of the presence of beta.-cyclodextrin on the micellization process of sodium dodecyl sulfate or sodium perfluorooctanoate in water. Langmuir 9:1213–1219

    Article  Google Scholar 

  • Kabanov AV, Batrakova EV, Alakhov VY (2002) Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 82:189–212

    Article  Google Scholar 

  • Kaewsaiha P, Matsumoto K, Matsuoka H (2005) Non-surface activity and micellization of ionic amphiphilic diblock copolymers in water. Hydrophobic chain length dependence and salt effect on surface activity and the critical micelle concentration. Langmuir 21:9938–9945

    Article  Google Scholar 

  • Kakizawa Y, Harada A, Kataoka K (1999) Environment-sensitive stabilization of core–shell structured polyion complex micelle by reversible cross-linking of the core through disulfide bond. J Am Chem Soc 121:11247–11248

    Article  Google Scholar 

  • Kalyanasundaram K, Thomas JK (1977) Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems. J Am Chem Soc 99:2039–2044

    Article  Google Scholar 

  • Kannan RM, Nance E, Kannan S et al (2014) Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med 276:579–617

    Article  Google Scholar 

  • Kataoka K, Harada A, Nagasaki Y (2001) Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 47:113–131

    Article  Google Scholar 

  • Kim HU, Lim KH (2003) Description of temperature dependence of critical micelle concentration. Bull Korean Chem Soc 24:1449–1454

    Article  Google Scholar 

  • Kim S, Kim JY, Huh KM, Acharya G, Park K (2008) Hydrotropic polymer micelles containing acrylic acid moieties for oral delivery of paclitaxel. J Control Release 132:222–229

    Article  Google Scholar 

  • Kim JO, Kabanov AV, Bronich TK (2009) Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin. J Control Release 138:197–204

    Article  Google Scholar 

  • Kim S, Shi Y, Ji YK, Park K, Cheng JX (2010a) Overcoming the barriers in micellar drug delivery: loading efficiency, in vivo stability, and micelle-cell interaction. Expert Opin Drug Deliv 7:49–62

    Article  Google Scholar 

  • Kim SH et al (2010b) Hydrogen bonding-enhanced micelle assemblies for drug delivery. Biomaterials 31:8063–8071

    Article  Google Scholar 

  • Kim JO, Ramasamy T, Yong CS, Nukolov NV, Bronich TK, Kabanov AV (2013) Cross-linked polymeric micelles based on block ionomer complexes. Mendeleev Commun 23:179–186

    Article  Google Scholar 

  • Koo AN et al (2008) Disulfide-cross-linked PEG-poly (amino acid)s copolymer micelles for glutathione-mediated intracellular drug delivery. Chem Commun 48:6570–6572

    Article  Google Scholar 

  • Kore G, Kolate A, Nej A, Misra A (2014) Polymeric micelle as multifunctional pharmaceutical carriers. J Nanosci Nanotechnol 14:288–307

    Article  Google Scholar 

  • Lai PL, Hsu CC, Liu TH, Hong DW, Chen LH, Chen WJ, Chu IM (2012) Mixed micelles from methoxy poly (ethylene glycol)-polylactide and methoxy poly (ethylene glycol)-poly (sebacic anhydride) copolymers as drug carriers. React Funct Polym 72:846–855

    Article  Google Scholar 

  • Lavasanifar A, Samuel J, Kwon GS (2002) The effect of fatty acid substitution on the in vitro release of amphotericin B from micelles composed of poly (ethylene oxide)-block-poly (N-hexyl stearate-l-aspartamide). J Control Release 79:165–172

    Article  Google Scholar 

  • Lee JS, Feijen J (2012) Polymersomes for drug delivery: design, formation and characterization. J Control Release 161:473–483

    Article  Google Scholar 

  • Lee YS, Woo KW (1995) Micellization of Aqueous Cationic Surfactant Solutions at the Micellar Structure Transition Concentration-Based upon the Concept of the Pseudophase Separation. J Colloid Interface Sci 169:34–38

    Article  Google Scholar 

  • Lee HJ, Ponta A, Bae Y (2010) Polymer nanoassemblies for cancer treatment and imaging. Ther Deliv 1:803–817

    Article  Google Scholar 

  • Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65:259–269

    Article  Google Scholar 

  • Li G, Guo L, Meng Y, Zhang T (2011) Self-assembled nanoparticles from thermo-sensitive polyion complex micelles for controlled drug release. Chem Eng J 174:199–205

    Article  Google Scholar 

  • Li M, Liu Y, Feng L, Liu F, Zhang L, Zhang N (2015) Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery. Colloids Surf B Biointerfaces 131:191–201

    Article  Google Scholar 

  • Liang J, Wu WL, Xu XD, Zhuo RX, Zhang XZ (2014) pH Responsive micelle self-assembled from a new amphiphilic peptide as anti-tumor drug carrier. Colloids Surf B Biointerfaces 114:398–403

    Article  Google Scholar 

  • Liu J, Xiao Y, Allen C (2004) Polymer-drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine. J Pharm Sci 93:132–143

    Article  Google Scholar 

  • Liu J, Zeng F, Allen C (2005) Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent. J Control Release 103:481–497

    Article  Google Scholar 

  • Liu J, Zeng F, Allen C (2007) In vivo fate of unimers and micelles of a poly (ethylene glycol)-block-poly (caprolactone) copolymer in mice following intravenous administration. Eur J Pharm Biopharm 65:309–319

    Article  Google Scholar 

  • Logie J, Owen SC, McLaughlin CK, Shoichet MS (2014) PEG-graft density controls polymeric nanoparticle micelle stability. Chem Mater 26:2847–2855

    Article  Google Scholar 

  • Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41:189–207

    Article  Google Scholar 

  • Mata JP, Majhi PR, Guo C, Liu HZ, Bahadur P (2005) Concentration, temperature, and salt-induced micellization of a triblock copolymer Pluronic L64 in aqueous media. J Colloid Interface Sci 292:548–556

    Article  Google Scholar 

  • Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15:171–185

    Article  Google Scholar 

  • Mero A, Clementi C, Veronese FM, Pasut G (2011) Covalent conjugation of poly (ethylene glycol) to proteins and peptides: strategies and methods. Methods Mol Biol 751:95–129

    Article  Google Scholar 

  • Miller T et al (2013) Premature drug release of polymeric micelles and its effects on tumor targeting. Int J Pharm 445:117–124

    Article  Google Scholar 

  • Mukerjee P, Mysels KJ (1971) Critical micelle concentrations of aqueous surfactant systems. DTIC Document No. NSRDS NBS 36:503–507

    Google Scholar 

  • Narang AS, Delmarre D, Gao D (2007) Stable drug encapsulation in micelles and microemulsions. Int J Pharm 345:9–25

    Article  Google Scholar 

  • Ni C, Zhu G, Zhu C, Yao B, Kumar DNT (2010) Studies on core-shell structural nano-micelles based on star block copolymer of poly (lactide) and poly (2-(dimethylamino) ethyl methacrylate). Colloid Polym Sci 288:1193–1200

    Article  Google Scholar 

  • Nolan SL, Phillips RJ, Cotts PM, Dungan SR (1997) Light scattering study on the effect of polymer composition on the structural properties of PEO–PPO–PEO micelles. J Colloid Interface Sci 191:291–302

    Article  Google Scholar 

  • Owen SC, Chan DPY, Shoichet MS (2012) Polymeric micelle stability. Nano Today 7:53–65

    Article  Google Scholar 

  • Patel SK, Lavasanifar A, Choi P (2009) Roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of PEO-b-PCL with increasing PCL content for two hydrophobic cucurbitacin drugs. Biomacromolecules 10:2584–2591

    Article  Google Scholar 

  • Pati D, Kalva N, Das S, Kumaraswamy G, Sen Gupta S, Ambade AV (2012) Multiple topologies from glycopolypeptide-dendron conjugate self-assembly: nanorods, micelles, and organogels. J Am Chem Soc 134:7796–7802

    Article  Google Scholar 

  • Pimm M, Perkins A, Duncan R, Ulbrich K (1993) Targeting of N-(2-hydroxypropyl) methacrylamide copolymer-doxorubicin conjugate to the hepatocyte galactose-receptor in mice: visualisation and quantification by gamma scintigraphy as a basis for clinical targeting studies. J Drug Target 1:125–131

    Article  Google Scholar 

  • Poon Z, Lee JA, Huang S, Prevost RJ, Hammond PT (2011) Highly stable, ligand-clustered “patchy” micelle nanocarriers for systemic tumor targeting. Nanomedicine 7:201–209

    Google Scholar 

  • Portinha D, Bouteiller L, Pensec S, Richez A, Chassenieux C (2004) Influence of preparation conditions on the self-assembly by stereocomplexation of polylactide containing diblock copolymers. Macromolecules 37:3401–3406

    Article  Google Scholar 

  • Price C, Booth C, Canham PA, Naylor TdV, Stubbersfield RB (1984) The thermodynamics of micelle formation by a polystyrene-b-polyisoprene block copolymer in N, N′-dimethylacetamide. Br polymer J 16:311–313

    Article  Google Scholar 

  • Quan CY, Wei H, Shi Y, Li ZY, Cheng SX, Zhang XZ, Zhuo RX (2011) Fabrication of multifunctional shell cross-linked micelles for targeting drug release. Colloid Polym Sci 289:667–675

    Article  Google Scholar 

  • Raffa P, Stuart MC, Broekhuis AA, Picchioni F (2014) The effect of hydrophilic and hydrophobic block length on the rheology of amphiphilic diblock Polystyrene-b-Poly(sodium methacrylate) copolymers prepared by ATRP. J Colloid Interface Sci 428:152–161

    Article  Google Scholar 

  • Rapoport N (2007) Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery. Prog Polym Sci 32:962–990

    Article  Google Scholar 

  • Read ES, Armes SP (2007) Recent advances in shell cross-linked micelles. Chem Commun 29:3021–3035

    Article  Google Scholar 

  • Ren J et al (2013) pH/sugar dual responsive core-cross-linked PIC micelles for enhanced intracellular protein delivery. Biomacromolecules 14:3434–3443

    Article  Google Scholar 

  • Riley T, Govender T, Stolnik S, Xiong CD, Garnett MC, Illum L, Davis SS (1999) Colloidal stability and drug incorporation aspects of micellar-like PLA–PEG nanoparticles. Colloids Surf B Biointerfaces 16:147–159

    Article  Google Scholar 

  • Sagnella SM, McCarroll JA, Kavallaris M (2014) Drug delivery: beyond active tumour targeting. Nanomedicine 10:1131–1137

    Google Scholar 

  • Santos AP, Panagiotopoulos AZ (2016) Determination of the critical micelle concentration in simulations of surfactant systems. J Chem Phys 144(044709):1–9

    Google Scholar 

  • Shao Y, Huang W, Shi C, Atkinson ST, Luo J (2012) Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment. Ther Deliv 3:1409–1427

    Article  Google Scholar 

  • Suchao-in N, Chirachanchai S, Perrier S (2009) pH-and thermo-multi-responsive fluorescent micelles from block copolymers via reversible addition fragmentation chain transfer (RAFT) polymerization. Polymer 50:4151–4158

    Article  Google Scholar 

  • Sun H, Guo B, Cheng R, Meng F, Liu H, Zhong Z (2009) Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials 30:6358–6366

    Article  Google Scholar 

  • Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications-reflections on the field. Adv Drug Deliv Rev 57:2106–2129

    Article  Google Scholar 

  • Talelli M, Rijcken C, Van Nostrum C, Storm G, Hennink W (2010) Micelles based on HPMA copolymers. Adv Drug Deliv Rev 62:231–239

    Article  Google Scholar 

  • Tan SW, Wang HJ, Tu KH, Jiang HL, Wang LQ (2011) Ibuprofen induced drug loaded polymeric micelles. Chin Chem Lett 22:1123–1126

    Article  Google Scholar 

  • Thambi T, Deepagan V, Ko H, Lee DS, Park JH (2012) Bioreducible polymersomes for intracellular dual-drug delivery. J Mater Chem 22:22028–22036

    Article  Google Scholar 

  • Tian Y, Mao S (2012) Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs. Expert Opin Drug Deliv 9:687–700

    Article  Google Scholar 

  • Tomalia DA, Christensen JB, Boas U (2012) Dendrimers, dendrons, and dendritic polymers: discovery, applications, and the future. Cambridge University Press, Cambridge

    Book  Google Scholar 

  • Toomey R, Mays J, Tirrell M (2006) The role of salt in governing the adsorption mechanisms of micelle-forming polyelectrolyte/neutral diblock copolymers. Macromolecules 39:697–702

    Article  Google Scholar 

  • Torchilin VP (2002) PEG-based micelles as carriers of contrast agents for different imaging modalities. Adv Drug Deliv Rev 54:235–252

    Article  Google Scholar 

  • Tsuji H (2005) Poly(lactide) stereocomplexes: formation, structure, properties, degradation, and applications. Macromol Biosci 5:569–597

    Article  Google Scholar 

  • Ukawala M et al (2012) Investigation on design of stable etoposide-loaded PEG–PCL micelles: effect of molecular weight of PEG–PCL diblock copolymer on the in vitro and in vivo performance of micelles. Drug Deliv 19:155–167

    Article  Google Scholar 

  • Veronese FM et al (2005) PEG-doxorubicin conjugates: influence of polymer structure on drug release, in vitro cytotoxicity, biodistribution, and antitumor activity. Bioconjug Chem 16:775–784

    Article  Google Scholar 

  • Wang Y, Li Y, Wang Q, Wu J, Fang X (2008) Pharmacokinetics and biodistribution of paclitaxel-loaded pluronic P105/L101 mixed polymeric micelles. Yakugaku Zasshi 128:941–950

    Article  Google Scholar 

  • Wang S, Yuan F, Jiang H, Wang L (2014a) Construction of chitosan micelles by chemical modification method and their photo-responsive characteristics. J Funct Polym 1:17–22

    Google Scholar 

  • Wang X, Li L, Ye X, Wu C (2014b) Comparative study of solution properties of amphiphilic 8-shaped cyclic-(polystyrene-b-poly(acrylic acid))2 and its linear precursor. Macromolecules 47:2487–2495

    Article  Google Scholar 

  • Wang J, Xu W, Guo H, Ding J, Chen J, Guan J, Wang C (2015) Selective intracellular drug delivery from pH-responsive polyion complex micelle for enhanced malignancy suppression in vivo. Colloids Surf B Biointerfaces 135:283–290

    Article  Google Scholar 

  • Watanabe M, Kawano K, Yokoyama M, Opanasopit P, Okano T, Maitani Y (2006) Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability. Int J Pharmaceut 308:183–189

    Article  Google Scholar 

  • Yang L, Alexandridis P (2000) Physicochemical aspects of drug delivery and release from polymer-based colloids. Curr Opin Colloid in 5:132–143

    Article  Google Scholar 

  • Yang C, Attia ABE, Tan JP, Ke X, Gao S, Hedrick JL, Yang YY (2012) The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles. Biomaterials 33:2971–2979

    Article  Google Scholar 

  • Yokoyama M, Okano T, Sakurai Y, Kataoka K (1994) Improved synthesis of adriamycin-conjugated poly(ethylene oxide)-poly(aspartic acid) block copolymer and formation of unimodal micellar structure with controlled amount of physically entrapped adriamycin. J Control Release 32:269–277

    Article  Google Scholar 

  • Yu C et al (2013) The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells. Biomaterials 34:6284–6298

    Article  Google Scholar 

  • Zhang H, Sun X, Wang X, Zhou QF (2005) Synthesis of a novel ABC triblock copolymer with a rigid-rod block via atom transfer radical polymerization. Macromol Rapid Commun 26:407–411

    Article  Google Scholar 

  • Zhang L, Liu W, Lin L, Chen D, Stenzel MH (2008) Degradable disulfide core-cross-linked micelles as a drug delivery system prepared from vinyl functionalized nucleosides via the RAFT process. Biomacromolecules 9:3321–3331

    Article  Google Scholar 

  • Zhang X, Ai C, Ma J, Xu J, Yang S (2011) Synthesis of zwitterionic shell cross-linked micelles with pH-dependent hydrophilicity. J Colloid Interface Sci 356:24–30

    Article  Google Scholar 

  • Zhang S et al (2014) Self-assembly of amphiphilic Janus dendrimers into uniform onion-like dendrimersomes with predictable size and number of bilayers. Proc Natl Acad Sci 111:9058–9063

    Article  Google Scholar 

  • Zhao X, Poon Z, Engler AC, Bonner DK, Hammond PT (2012) Enhanced stability of polymeric micelles based on postfunctionalized poly(ethylene glycol)-b-poly(γ-propargyl l-glutamate): the substituent effect. Biomacromolecules 13:1315–1322

    Article  Google Scholar 

  • Zhong WY, Ling FX, Ya juan Li, Wen ZZ, Mei HL, Yi SX (2008) Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric micelles and in vitro reversal of multidrug resistant tumor. Acta Pharm Sin 43:640–646

    Google Scholar 

  • Zhu Z, Xu J, Zhou Y, Jiang X, Armes SP, Liu S (2007) Effect of salt on the micellization kinetics of pH-responsive ABC triblock copolymers. Macromolecules 40:6393–6400

    Article  Google Scholar 

Download references

Acknowledgments

This study is financially supported by the National Science Foundation Grant of China (No. 81503005), the Natural Science Fundation of Jiangsu Province (No. BK20140669), and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Wenli Zhang or Jianping Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, W., Li, C., Wang, Z. et al. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement. J Nanopart Res 18, 275 (2016). https://doi.org/10.1007/s11051-016-3583-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-016-3583-y

Keywords

Navigation