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Frontiers of Materials Science

ISSN 2095-025X

ISSN 2095-0268(Online)

CN 11-5985/TB

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Front. Mater. Sci.    2018, Vol. 12 Issue (1) : 83-94    https://doi.org/10.1007/s11706-018-0407-2
RESEARCH ARTICLE
Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin
Amina Ben MIHOUB1,2, Boubakeur SAIDAT2, Youssef BAL3,4, Céline FROCHOT5, Régis VANDERESSE1, Samir ACHERAR1()
1. Laboratoire de Chimie Physique Macromoléculaire (LCPM), Université de Lorraine-CNRS, UMR 7375, 1 Rue Grandville, BP 20451, 54001, Nancy Cedex, France
2. Laboratory of Physical Chemistry of Materials (LPCM), Faculty of Sciences, (UATL) BP 37G Laghouat 03000, Algeria
3. Laboratory of Biomaterials & Transport Phenomena (LBTP), Quartier Ain D’Heb, 26000, Medea, Algeria
4. Department of Chemistry, Faculty of Sciences, University Saéd Dahleb of Blida (USDB), route de Soumaé, 09000, Blida, Algeria
5. Laboratoire Réactions et Génie des Procédés (LRGP), Université de Lorraine-CNRS, UMR 7274, 1 Rue Grandville, BP 20451, 54001, Nancy Cedex, France
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Abstract

In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD-g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA/β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA):w(β-CD-g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β-CD-g-CS NPs and HA/β-CD-g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.
Keywords β-cyclodextrin-grafted chitosan      hyaluronic acid      ionic gelation      drug delivery      physicochemical parameters control     
Corresponding Author(s): Samir ACHERAR   
Online First Date: 11 January 2018    Issue Date: 08 March 2018
 Cite this article:   
Amina Ben MIHOUB,Boubakeur SAIDAT,Youssef BAL, et al. Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin[J]. Front. Mater. Sci., 2018, 12(1): 83-94.
 URL:  
https://academic.hep.com.cn/foms/EN/10.1007/s11706-018-0407-2
https://academic.hep.com.cn/foms/EN/Y2018/V12/I1/83
Fig.1  Syntheses of (a) intermediate Ts-β-CD and (b)β-CD-g-CS copolymer.
Fig.2  FTIR spectra of β-CD, Ts-β-CD, CS and β-CD-g-CS copolymer.
Product Refs. Wavenumber/cm−1 Functional group
β-CD [28,30] 2922 and 1413 C−H stretching and O−H bending
1019, 1100 and 1150 C−O−C symmetric stretching
3277 O−H stretching
940 α-1,4 linkage skeletal vibration
Ts-β-CD [28,31] 1599 C=C stretching of benzene
1153 S=O stretching
941 α-1,4 linkage skeletal vibration
CS [28,30?31] 3200?3600 O−H and NH2 stretching
2921 and 2869 C−H stretching
1644 C=O and C−O stretch amide group
1156?1024 C−O−C and C−O stretching
1585 NH2 deformation
893 β-pyranyl vibration
Tab.1  IR absorption bands attribution for β-CD, Ts-β-CD and CS
Fig.3  1H NMR spectra of (a)β-CD in DMSO-d6, (b) Ts-β-CD in DMSO-d6, and (c)β-CD-g-CS in D2O.
Fig.4  XRD patterns of CS and β-CD-g-CS copolymer.
Trial pH c(β-CD-g-CS)/(mg·mL−1) n(β-CD-g-CS)/n(STPP) Particle size/nm PZ/mV PDI
A1 3 1 5/1 nd a) nd a) nd a)
A2 3.5 1 4/1 218.7 +37.6 0.24
A3 3.5 1 5/1 202.1 +40.9 0.22
A4 4 0.5 5/1 nd a) nd a) nd a)
A5 4 1 5/1 239.7 +36.2 0.25
A8 5 1 5/1 225.7 +32.1 0.17
A9 5 1 4/1 245.7 +29.0 0.33
A10 5 1.5 4/1 nd b) nd b) nd b)
A11 5 1.5 6/1 352.8 +25.1 0.24
Tab.2  Physicochemical properties of β-CD-g-CS NPs
Fig.5  Schematic representation of the formation process of HA/β-CD-g-CS NPs.
Trial Particle size/nm ZP/mV PDI
A3 a) 202.11 +40.9 0.220
B1 b) 191.20 +41.7 0.193
B2 c) 187.17 +31.3 0.175
B3 b)c) 175.96 +31.5 0.070
Tab.3  Effect of 150 mmol/L NaCl+10 mmol/L HEPES mixture and ultrasonication on the size distribution, PDI and ZP control of β-CD-g-CS NPs
Fig.6  (a) Particle size distribution and (b) ZP histograms of B3 in Table 3.
Trial w(HA):w(β-CD-g-CS) Particle size/nm ZP/mV PDI Appearance
B3 a) 0:1 175.96 +31.5 0.070 medium opacity
C1 1:2 182.23 +25.8 0.210 medium opacity
C2 1:1 205.01 +17.8 0.352 high opacity
C3 2:1 193.20 −31.0 0.122 medium opacity
C4 3:1 nd nd nd low opacity
Tab.4  Characteristics of HA/β-CD-g-CS NPs with different w(HA):w(β-CD-g-CS) weight ratios
Fig.7  (a) Particle size distribution and (b) ZP histograms of C3 in Table 4.
NPs Storage period/week Particle size/nm ZP/mV PDI
β-CD-g-CS 0 175.96 +31.5 0.07
1 181.32 +30.4 0.252
2 210.21 +28.7 0.341
3 217.11 +25.1 0.401
HA/β-CD-g-CS 0 193.20 −31.7 0.122
1 200.23 −31.5 0.149
2 212.71 −30.2 0.205
3 220.17 −29.8 0.227
Tab.5  HA effect on β-CD-g-CS and HA/β-CD-g-CS NPs stability at 4°C in physiological media (pH 7.4)
Fig.8  (a) TEM and (b) SEM images of HA/β-CD-g-CS NPs.
NPs Size/nm ZP/mV PDI EE/%
Dox-HA/β-CD-g-CS 220.1 −28.2 0.183 47.6
Tab.6  Physicochemical properties of Dox-HA/β-CD-g-CS NPs
Fig.9  In vitro cumulative release of Dox from HA/β-CD-g-CS NPs at 37°C in acetate buffer solution (pH 4.6).
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