Skip to main content

Advertisement

Log in

Preparation of pH- and thermo-sensitive chitosan-PNIPAAm core–shell nanoparticles and evaluation as drug carriers

  • Original Paper
  • Published:
Cellulose Aims and scope Submit manuscript

Abstract

Environmentally sensitive polysaccharide nanoparticles (NPs) were prepared by in situ polymerization of N-isopropylacrylamide (NIPAAm) monomer in the presence of chitosan (CS) micelles. First, CS was found to develop a cationic micelle-like structure in the acetic acid solution when its concentration was increased to above the critical micelle concentration, as evidenced by fluorescence and TEM. When the NIPAAm was polymerized in the CS micelle solution by using potassium persulfate as initiator, the produced PNIPAAm with anionic chain end(s) became hydrophobic, as long as the reaction temperature was above its phase transition temperature; and therefore it would diffuse into the hydrophobic core of the CS micelles, producing CS-PNIPAAm core–shell NPs. Increasing the feeding amount of NIPAAm increased the monomer conversion and therefore the particle size; yet it decreased the surface zeta potential. Moreover, the CS-PNIPAAm NPs were sensitive to both pH value and temperature. For the study of drug release properties, doxycycline hyclate was used as a model drug and loaded into the NPs at pH 4.5 and 25 °C. The result illustrated that these NPs had a continuous drug release behavior up to 1 week, depending on the pH value and temperature. In addition, enzyme or hydrogen peroxide capable of degrading CS shell was added in the solution to facilitate the drug release.

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.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Scheme 2
Fig. 10

Similar content being viewed by others

References

  • Aktaş Y, Yemisci M, Andrieux K, Gürsoy RN, Alonso MJ, Fernandez-Megia E, Novoa-Carballal R, Quiñoá E, Riguera R, Sargon MF, Çelik HH, Demir AS, Hıncal AA, Dalkara T, Çapan Y, Couvreur P (2005) Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26. Bioconjug Chem 16(6):1503–1511

    Article  Google Scholar 

  • Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5(4):505–515

    Article  CAS  Google Scholar 

  • Amidi M, Romeijn SG, Borchard G, Junginger HE, Hennink WE, Jiskoot W (2006) Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release 111(1–2):107–116

    Article  CAS  Google Scholar 

  • Bae YH, Okano T, Kim SW (1990) Temperature dependence of swelling of crosslinked poly(N,N-alkyl substituted acrylamides) in water. J Polym Sci B Polym Phys 28(6):923–936

    Article  CAS  Google Scholar 

  • Berth G, Voigt A, Dautzenberg H, Donath E, Mohwald H (2002) Polyelectrolyte complexes and layer-by-layer capsules from chitosan/chitosan sulfate. Biomacromolecules 3(3):579–590

    Article  CAS  Google Scholar 

  • Binkert T, Oberreich J, Meewes M, Nyffenegger R, Ricka J (1991) Coil-globule transition of poly(N-isopropylacrylamide): a study of segment mobility by fluorescence depolarization. Macromolecules 24(21):5806–5810

    Article  CAS  Google Scholar 

  • Bodnar M, Hartmann JF, Borbely J (2005a) Nanoparticles from chitosan. Macromol Symp 227:321–326

    Article  CAS  Google Scholar 

  • Bodnar M, Hartmann JF, Borbely J (2005b) Preparation and characterization of chitosan-based nanoparticles. Biomacromolecules 6(5):2521–2527

    Article  CAS  Google Scholar 

  • Caruso F, Caruso RA, Mohwald H (1998) Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating. Science 282(5391):1111–1114

    Article  CAS  Google Scholar 

  • Chen GH, Hoffman AS (1995) Graft copolymers that exhibit temperature-induced phase transitions over a wide range of pH. Nature 373(6509):49–52

    Article  CAS  Google Scholar 

  • Chiu YL, Ho YC, Chen YM, Peng SF, Ke CJ, Chen KJ, Mi FL, Sung HW (2010) The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. J Control Release 146(1):152–159

    Article  CAS  Google Scholar 

  • Chuang CY, Chiu WY, Don TM (2011) Synthesis of chitosan-poly(Acrylic Acid) complex particles by dispersion polymerization and their applications in pH buffering and drug release. J Appl Polym Sci 120(3):1659–1670

    Article  CAS  Google Scholar 

  • Hotz J, Meier W (1998) Polymer particles by templating of vesicles. Adv Mater 10(16):1387–1390

    Article  CAS  Google Scholar 

  • Hu Y, Jiang XQ, Ding Y, Ge HX, Yuan YY, Yang CZ (2002) Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles. Biomaterials 23(15):3193–3201

    Article  CAS  Google Scholar 

  • Hu Y, Jiang XQ, Ding Y, Chen Q, Yang CZ (2004) Core-template-free strategy for preparing hollow nanospheres. Adv Mater 16(11):933–937

    Article  CAS  Google Scholar 

  • Hu Y, Chen Y, Chen Q, Zhang L, Jiang X, Yang C (2005) Synthesis and stimuli-responsive properties of chitosan/poly(acrylic acid) hollow nanospheres. Polymer 46(26):12703–12710

    Article  CAS  Google Scholar 

  • Hu Y, Ding Y, Ding D, Sun M, Zhang L, Jiang X, Yang C (2007) Hollow chitosan/poly(acrylic acid) nanospheres as drug carriers. Biomacromolecules 8(4):1069–1076

    Article  CAS  Google Scholar 

  • Jiang H-L, Kim Y-K, Arote R, Nah J-W, Cho M-H, Choi Y-J, Akaike T, Cho C-S (2007) Chitosan-graft-polyethylenimine as a gene carrier. J Control Release 117(2):273–280

    Article  CAS  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(7):2039–2044

    Article  CAS  Google Scholar 

  • Kjøniksen A-L, Iversen C, Nyström B, Nakken T, Palmgren O (1998) Light scattering study of semidilute aqueous systems of chitosan and hydrophobically modified chitosans. Macromolecules 31(23):8142–8148

    Article  Google Scholar 

  • Langer R, Tirrell DA (2004) Designing materials for biology and medicine. Nature 428(6982):487–492

    Article  CAS  Google Scholar 

  • Lee CF, Wen CJ, Lin CL, Chiu WY (2004) Morphology and temperature responsiveness-swelling relationship of poly(N-isopropylamide-chitosan) copolymers and their application to drug release. J Polym Sci A Polym Chem 42(12):3029–3037

    Article  CAS  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(3):259–269

    Article  CAS  Google Scholar 

  • Li H, Huo M, Zhou J, Dai Y, Deng Y, Shi X, Masoud J (2010) Enhanced oral absorption of paclitaxel in N-deoxycholic acid-N, O-hydroxyethyl chitosan micellar system. J Pharm Sci 99(11):4543–4553

    Article  CAS  Google Scholar 

  • Lin Y-H, Chung C-K, Chen C-T, Liang H-F, Chen S-C, Sung H-W (2005) Preparation of nanoparticles composed of chitosan/poly-γ-glutamic acid and evaluation of their permeability through Caco-2 cells. Biomacromolecules 6(2):1104–1112

    Article  CAS  Google Scholar 

  • Lin M-C, Tai H-Y, Ou T-C, Don T-M (2012) Preparation and characterization of UV-sensitive chitosan for UV-cure with poly(ethylene glycol) dimethacrylate. Cellulose 19(5):1689–1700

    Article  CAS  Google Scholar 

  • Liu CG, Desai KG, Chen XG, Park HJ (2005) Preparation and characterization of nanoparticles containing trypsin based on hydrophobically modified chitosan. J Agric Food Chem 53(5):1728–1733

    Article  CAS  Google Scholar 

  • Liu H, Chen B, Mao Z, Gao C (2007) Chitosan nanoparticles for loading of toothpaste actives and adhesion on tooth analogs. J Appl Polym Sci 106(6):4248–4256

    Article  CAS  Google Scholar 

  • Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z (2008) Polysaccharides-based nanoparticles as drug delivery systems. Adv Drug Deliv Rev 60(15):1650–1662

    Article  CAS  Google Scholar 

  • Liu Y, Kong M, Feng C, Yang KK, Li Y, Su J, Cheng XJ, Park HJ, Chen XG (2012) Biocompatibility, cellular uptake and biodistribution of the polymeric amphiphilic nanoparticles as oral drug carriers. Colloids Surf B Biointerfaces 103C:345–353

    Google Scholar 

  • Moyuan C, Haixia J, Weijuan Y, Peng L, Liqun W, Hongliang J (2012) A convenient scheme for synthesizing reduction-sensitive chitosan-based amphiphilic copolymers for drug delivery. J Appl Polym Sci 123(5):3137–3144

    Article  Google Scholar 

  • Ortona O, D’Errico G, Mangiapia G, Ciccarelli D (2008) The aggregative behavior of hydrophobically modified chitosans with high substitution degree in aqueous solution. Carbohydr Polym 74(1):16–22

    Article  CAS  Google Scholar 

  • Rejinold NS, Chennazhi KP, Nair SV, Tamura H, Jayakumar R (2011a) Biodegradable and thermo-sensitive chitosan-g-poly(N-vinylcaprolactam) nanoparticles as a 5-fluorouracil carrier. Carbohydr Polym 83(2):776–786

    Article  CAS  Google Scholar 

  • Rejinold NS, Muthunarayanan M, Divyarani VV, Sreerekha PR, Chennazhi KP, Nair SV, Tamura H, Jayakumar R (2011b) Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles for cancer drug delivery. J Colloid Interface Sci 360(1):39–51

    Article  Google Scholar 

  • Rejinold NS, Sreerekha PR, Chennazhi KP, Nair SV, Jayakumar R (2011c) Biocompatible, biodegradable and thermo-sensitive chitosan-g-poly (N-isopropylacrylamide) nanocarrier for curcumin drug delivery. Int J Biol Macromol 49(2):161–172

    Article  Google Scholar 

  • Rinaudo M, Pavlov G, Desbrieres J (1999) Influence of acetic acid concentration on the solubilization of chitosan. Polymer 40(25):7029–7032

    Article  CAS  Google Scholar 

  • Sarmento B, Ferreira D, Veiga F, Ribeiro A (2006) Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydr Polym 66(1):1–7

    Article  CAS  Google Scholar 

  • Sarmento B, Ferreira DC, Jorgensen L, van de Weert M (2007) Probing insulin’s secondary structure after entrapment into alginate/chitosan nanoparticles. Eur J Pharm Biopharm 65(1):10–17

    Article  CAS  Google Scholar 

  • Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17(2):163–249

    Article  CAS  Google Scholar 

  • Wang M, Fang Y, Hu D (2001) Preparation and properties of chitosan-poly(N-isopropylacrylamide) full-IPN hydrogels. React Funct Polym 48(1–3):215–221

    Article  CAS  Google Scholar 

  • Wang K, Zhang T, Liu L, Wang X, Wu P, Chen Z, Ni C, Zhang J, Hu F, Huang J (2012) Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells. Int J Nanomed 7:4487–4497

    CAS  Google Scholar 

  • Wilhelm M, Zhao CL, Wang YC, Xu RL, Winnik MA, Mura JL, Riess G, Croucher MD (1991) Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study. Macromolecules 24(5):1033–1040

    Article  CAS  Google Scholar 

  • Worthington CC (1988) Worthington enzyme manual: enzymes and related biochemicals. Worthington Biochemical Corporation, Lakewood, NJ

    Google Scholar 

  • Xia WS, Liu P, Liu J (2008) Advance in chitosan hydrolysis by non-specific cellulases. Bioresource Technol 99(15):6751–6762

    Article  CAS  Google Scholar 

  • Yoksan R, Matsusaki M, Akashi M, Chirachanchai S (2004) Controlled hydrophobic/hydrophilic chitosan: colloidal phenomena and nanosphere formation. Colloid Polym Sci 282(4):337–342

    Article  CAS  Google Scholar 

  • Zhang H, Oh M, Allen C, Kumacheva E (2004) Monodisperse chitosan nanoparticles for mucosal drug delivery. Biomacromolecules 5(6):2461–2468

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Science Council (NSC 99-2221-E-002-019-MY3).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Trong-Ming Don or Wen-Yen Chiu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, CH., Wang, CF., Don, TM. et al. Preparation of pH- and thermo-sensitive chitosan-PNIPAAm core–shell nanoparticles and evaluation as drug carriers. Cellulose 20, 1791–1805 (2013). https://doi.org/10.1007/s10570-013-9951-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10570-013-9951-1

Keywords

Navigation