Characterization of chitosan/alginate/lovastatin nanoparticles and investigation of their toxic effects in vitro and in vivo View Full Text


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Article Info

DATE

2020-01-22

AUTHORS

Hoang Thai, Chinh Thuy Nguyen, Loc Thi Thach, Mai Thi Tran, Huynh Duc Mai, Trang Thi Thu Nguyen, Giang Duc Le, Mao Van Can, Lam Dai Tran, Giang Long Bach, Kavitha Ramadass, C. I. Sathish, Quan Van Le

ABSTRACT

In this study, chitosan and alginate were selected to prepare alginate/chitosan nanoparticles to load the drug lovastatin by the ionic gelation method. The synthesized nanoparticles loaded with drug were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), laser scattering and differential scanning calorimetry (DSC) methods. The FTIR spectrum of the alginate/chitosan/lovastatin nanoparticles showed that chitosan and alginate interacted with lovastatin through hydrogen bonding and dipolar-dipolar interactions between the C-O, C=O, and OH groups in lovastatin, the C-O, NH, and OH groups in chitosan and the C-O, C=O, and OH groups in alginate. The laser scattering results and SEM images indicated that the alginate/chitosan/lovastatin nanoparticles have a spherical shape with a particle size in the range of 50-80 nm. The DSC diagrams displayed that the melting temperature of the alginate/chitosan/lovastatin nanoparticles was higher than that of chitosan and lower than that of alginate. This result means that the alginate and chitosan interact together, so that the nanoparticles have a larger crystal degree when compared with alginate and chitosan individually. Investigations of the in vitro lovastatin release from the alginate/chitosan/lovastatin nanoparticles under different conditions, including different alginate/chitosan ratios, different solution pH values and different lovastatin contents, were carried out by ultraviolet-visible spectroscopy. The rate of drug release from the nanoparticles is proportional to the increase in the solution pH and inversely proportional to the content of the loaded lovastatin. The drug release process is divided into two stages: a rapid stage over the first 10 hr, then the release becomes gradual and stable. The Korsmeyer-Peppas model is most suitable for the lovastatin release process from the alginate/chitosan/lovastatin nanoparticles in the first stage, and then the drug release complies with other models depending on solution pH in the slow release stage. In addition, the toxicity of alginate/chitosan/lovastatin (abbreviated ACL) nanoparticles was sufficiently low in mice in the acute toxicity test. The LD50 of the drug was higher than 5000 mg/kg, while in the subchronic toxicity test with treatments of 100 mg/kg and 300 mg/kg ACL nanoparticles, there were no abnormal signs, mortality, or toxicity in general to the function or structure of the crucial organs. The results show that the ACL nanoparticles are safe in mice and that these composite nanoparticles might be useful as a new drug carrier. More... »

PAGES

909

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-57666-8

DOI

http://dx.doi.org/10.1038/s41598-020-57666-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1124217635

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31969608


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22 schema:description In this study, chitosan and alginate were selected to prepare alginate/chitosan nanoparticles to load the drug lovastatin by the ionic gelation method. The synthesized nanoparticles loaded with drug were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), laser scattering and differential scanning calorimetry (DSC) methods. The FTIR spectrum of the alginate/chitosan/lovastatin nanoparticles showed that chitosan and alginate interacted with lovastatin through hydrogen bonding and dipolar-dipolar interactions between the C-O, C=O, and OH groups in lovastatin, the C-O, NH, and OH groups in chitosan and the C-O, C=O, and OH groups in alginate. The laser scattering results and SEM images indicated that the alginate/chitosan/lovastatin nanoparticles have a spherical shape with a particle size in the range of 50-80 nm. The DSC diagrams displayed that the melting temperature of the alginate/chitosan/lovastatin nanoparticles was higher than that of chitosan and lower than that of alginate. This result means that the alginate and chitosan interact together, so that the nanoparticles have a larger crystal degree when compared with alginate and chitosan individually. Investigations of the in vitro lovastatin release from the alginate/chitosan/lovastatin nanoparticles under different conditions, including different alginate/chitosan ratios, different solution pH values and different lovastatin contents, were carried out by ultraviolet-visible spectroscopy. The rate of drug release from the nanoparticles is proportional to the increase in the solution pH and inversely proportional to the content of the loaded lovastatin. The drug release process is divided into two stages: a rapid stage over the first 10 hr, then the release becomes gradual and stable. The Korsmeyer-Peppas model is most suitable for the lovastatin release process from the alginate/chitosan/lovastatin nanoparticles in the first stage, and then the drug release complies with other models depending on solution pH in the slow release stage. In addition, the toxicity of alginate/chitosan/lovastatin (abbreviated ACL) nanoparticles was sufficiently low in mice in the acute toxicity test. The LD<sub>50</sub> of the drug was higher than 5000 mg/kg, while in the subchronic toxicity test with treatments of 100 mg/kg and 300 mg/kg ACL nanoparticles, there were no abnormal signs, mortality, or toxicity in general to the function or structure of the crucial organs. The results show that the ACL nanoparticles are safe in mice and that these composite nanoparticles might be useful as a new drug carrier.
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30 DSC diagrams
31 FTIR spectra
32 Fourier transform
33 Korsmeyer-Peppas model
34 LD
35 NH
36 OH groups
37 SEM images
38 abnormal signs
39 acute toxicity test
40 addition
41 alginate
42 alginate/chitosan nanoparticles
43 alginate/chitosan ratios
44 alginate/chitosan/lovastatin nanoparticles
45 alginate/lovastatin nanoparticles
46 bonding
47 calorimetry method
48 carriers
49 characterization
50 chitosan
51 chitosan nanoparticles
52 chitosan ratio
53 chitosan/alginate/lovastatin nanoparticles
54 chitosan/lovastatin nanoparticles
55 complies
56 composite nanoparticles
57 conditions
58 content
59 crucial organ
60 crystal degree
61 degree
62 diagram
63 different alginate/chitosan ratios
64 different conditions
65 different lovastatin contents
66 different solution pH values
67 differential scanning calorimetry method
68 dipolar-dipolar interaction
69 drug carriers
70 drug lovastatin
71 drug release
72 drug release complies
73 drug release process
74 drugs
75 effect
76 electron microscopy
77 first stage
78 function
79 gelation method
80 group
81 hr
82 hydrogen bonding
83 images
84 increase
85 interaction
86 investigation
87 ionic gelation method
88 larger crystal degree
89 laser
90 laser scattering
91 loaded lovastatin
92 lovastatin
93 lovastatin content
94 lovastatin nanoparticles
95 lovastatin release
96 lovastatin release process
97 melting temperature
98 method
99 mice
100 microscopy
101 model
102 mortality
103 nanoparticles
104 new drug carrier
105 organs
106 pH
107 pH value
108 particle size
109 process
110 range
111 rapid stage
112 rate
113 ratio
114 release
115 release complies
116 release process
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118 results
119 scanning calorimetry method
120 scattering
121 shape
122 signs
123 size
124 slow release stage
125 solution pH
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127 spectra
128 spectroscopy
129 spherical shape
130 stage
131 structure
132 study
133 subchronic toxicity test
134 synthesized nanoparticles
135 temperature
136 test
137 toxic effects
138 toxicity
139 toxicity tests
140 transform
141 treatment
142 ultraviolet-visible spectroscopy
143 values
144 vivo
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