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Development of andrographolide-loaded solid lipid nanoparticles for lymphatic targeting: Formulation, optimization, characterization, in vitro, and in vivo evaluation

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Abstract

Andrographolide, the primary bioactive constituent of Andrographis paniculata, is a promising natural substance with numerous pharmacotherapy uses. Low water solubility, short half-life, and low permeability necessitate the development of a delivery system that enhances its entrapment efficiency, bioavailability, lymphatic targeting, and by-pass hepatic effect. The andrographolide-loaded solid lipid nanoparticles were fabricated by melt-emulsification and ultrasonication and optimized with Design-Expert software. In the optimal formulation, Glycerol monostearate as the solid lipid and Poloxamer 407 and Span 60 as surfactants were used. Optimum AND-SLN was observed to have a mean particle size, polydispersity index, zeta potential, and entrapment efficiency of 193.84 nm, 0.211, − 22.8 mV, and 83.70% respectively. An optimized formulation was characterized by examining surface morphology, X-ray diffraction, and differential scanning calorimetry. In vitro studies have shown sustained drug release from AND-SLN for up to 24 h. The stability studies showed that there was no significant change in the mean particle size and entrapment efficiency after storage at 4 ± 2 °C and 25 ± 2 °C/60 ± 5% RH. In in vivo pharmacokinetics studies, AND-SLN was found to have enhanced bioavailability and specificity in the spleen and thymus compared to plasma, providing evidence that the formulations could enhance target specificity and bioavailability in comparison to pure drugs. The H&E staining of the liver, spleen, and thymus treated with the AND-SLN revealed no signs of damage histopathologically. Thus, AND-SLN possess a high potential for improved efficacy and are an efficient vehicle for delivering drugs to the lymphatic system.

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Abbreviations

AND:

Andrographolide

AND-SLN:

Andrographolide-loaded solid lipid nanoparticles

AND-Susp:

Suspension of andrographolide

BBB:

Box–Behnken design

CPCSEA:

The Committee for the Purpose of Control and Supervision of Experiments on Animals

DLS:

 Dynamic light scattering

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FT-IR:

Fourier transform infrared spectroscopy

GMS:

Glycerol monostearate

H&E:

Hematoxylin and eosin

HPLC:

High-performance liquid chromatography

ICH:

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

PDI:

Polydispersity index

PS:

Particle size

RH:

Relative humidity

rpm:

Revolutions per minute

SD:

Standard deviation

SEM:

Scanning electron microscopy

SLNs:

Solid lipid nanoparticles

TEM:

Transmission electron microscopy

UV:

Ultraviolet

XRD:

X-ray diffraction

ZP:

Zeta potential

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Acknowledgements

The authors are grateful for the facilities provided by the Management and Principal of SRIP, Kumhari. We also recognize everyone who helped us conduct this research directly and indirectly.

Funding

The Chhattisgarh Council of Science & Technology in the form of a grant from the CCOST/MRP/1106/2015 and the CCOST/MRP/1120/2015 project, CGCOST, Raipur, Chhattisgarh, India, provided financial help for conducting these research projects.

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Authors and Affiliations

  1. Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh, India, 490042

    Saurabh Shrivastava

  2. Rungta College of Pharmaceutical Sciences and Research, Raipur, Chhattisgarh, India, 492009

    Chanchal Deep Kaur

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Contributions

Both authors contributed to framing the idea, studying the conception, and designing the manuscript. Conceptualization: (Saurabh Shrivastava), (Chanchal Deep Kaur); Methodology: (Saurabh Shrivastava); Software: (Saurabh Shrivastava); Formal analysis and investigation: (Saurabh Shrivastava); Writing—original draft preparation: (Saurabh Shrivastava), (Chanchal Deep Kaur); Writing—review and editing: (Saurabh Shrivastava), (Chanchal Deep Kaur); Funding acquisition: (Chanchal Deep Kaur); Resources: (Saurabh Shrivastava), (Chanchal Deep Kaur); Supervision: (Chanchal Deep Kaur).

Corresponding author

Correspondence to Saurabh Shrivastava.

Ethics declarations

Ethics approval and consent to participate

Experimental protocols were approved by the Institutional Animal Ethical Committee (SRIP/IAEC/2019–20/191/07), and studies were conducted under CPCSEA guidelines. Human subjects were not involved in this study, so there was no need for informed consent from the participants. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Competing interests

The authors declare no competing interests.

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The work originated in our lab. There is no conflict of interest among writers.

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Highlights

• Nanocarriers can improve the therapeutic profile of AND.

• The AND-SLN was prepared by melt-emulsification ultrasonication and optimized by Design-Expert software.

• An optimized formulation was characterized by DSC, XRD, and TEM.

• AND-SLN showed excellent in vitro and in vivo characteristics.

• AND-SLN is efficacious carriers of drugs targeting the lymphatic system with a high potential for improved efficacy.

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Shrivastava, S., Kaur, C.D. Development of andrographolide-loaded solid lipid nanoparticles for lymphatic targeting: Formulation, optimization, characterization, in vitro, and in vivo evaluation. Drug Deliv. and Transl. Res. 13, 658–674 (2023). https://doi.org/10.1007/s13346-022-01230-6

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