Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 22;10(1):909.
doi: 10.1038/s41598-020-57666-8.

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

Hoang Thai  1   2 , Chinh Thuy Nguyen  3 , Loc Thi Thach  4 , Mai Thi Tran  3 , Huynh Duc Mai  3 , Trang Thi Thu Nguyen  3 , Giang Duc Le  4 , Mao Van Can  5 , Lam Dai Tran  3   6 , Giang Long Bach  7 , Kavitha Ramadass  8 , C I Sathish  8 , Quan Van Le  9
Affiliations

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

Hoang Thai et al. Sci Rep. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Size distribution diagram of the ACL nanoparticles prepared with different AG/CS ratios.
Figure 2
Figure 2
Size distribution diagram of the ACL nanoparticles prepared with different LS contents.
Figure 3
Figure 3
SEM images of the (A) lovastatin; (B) AC6.5/3-L10; (C) AC6.5/3-L20; and (D) AC6.5/3-L30 samples.
Figure 4
Figure 4
FTIR spectra of the ACL nanoparticles prepared with different LS contents.
Figure 5
Figure 5
DSC diagrams of the CS, AG, LS (a), ACL nanoparticles with different AG/CS ratios (b) and ACL nanoparticles with different LS contents (c).
Figure 6
Figure 6
LS released from the ACL nanoparticles prepared with different AG/CS ratios in solution at pH 7.4.
Figure 7
Figure 7
LS released from (a) AC6.5/3-L10, (b) AC6.5/3-L20 and (c) AC6.5/3-L30 nanoparticles in different pH solutions.
Figure 8
Figure 8
LS released from the ACL nanoparticles in solution at pH 7.4.
Figure 9
Figure 9
LS released from the ACL nanoparticles at pH 6.5.
Figure 10
Figure 10
LS released from the ACL nanoparticles at pH 4.5.
Figure 11
Figure 11
LS released from the ACL nanoparticles at pH 2.
Figure 12
Figure 12
Kinetic equations fit to different models (Eqs. 1–5 in section 2.5), reflecting LS release from the AC6.5/3-L10 nanoparticles in pH 7.4 solution.
Figure 13
Figure 13
Histological changes in the livers of rats (without and with ACL nanoparticles) after the 28 day treatment period.
Figure 14
Figure 14
Histological changes in the kidneys of the three rat groups (without and with the use of ACL nanoparticles) after the 28 day treatment period.
See this image and copyright information in PMC

References

    1. Ochoa L, et al. Novel extended-release formulation of lovastatin by one-step melt granulation: In vitro and in vivo evaluation. Eur. J. Pharm. Biopharm. 2011;77:306–312. doi: 10.1016/j.ejpb.2010.11.024. - DOI - PubMed
    1. Sandhya P, Kodali G, Fatima A. Formulation and in-vitro characterization of gastro retentive mucoadhesive tablets of Lovastatin. Int. J. Biol. Pharm. Res. 2014;5(1):71–77.
    1. Anilkumar JS, Harinath NM. Lovastatin loaded chitosan nanoparticles: Preparation, evaluation and in vitro release studies. J. Pharm. Technol. 2011;4(12):1869–1876.
    1. Tarafder S, Nansen K, Bose S. Lovastatin release from polycaprolactone coated β-tricalcium phosphate: Effects of pH, concentration and drug–polymer interactions. Mater. Sci. Eng. C. 2013;33:3121–3128. doi: 10.1016/j.msec.2013.02.049. - DOI - PMC - PubMed
    1. Bor-Shiunne L, et al. Controlled-release of tetracycline and lovastatin by poly(d,l-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs. Int. J. Nanomed. 2016;11:285–297. - PMC - PubMed

Publication types