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Development and evaluation of polysorbate-80 coated Mangiferin PLGA nanoparticles used in the treatment of cerebral ischemia

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Abstract

To enhance Mangiferin (MNG) the brain bioavailability by developed novel polysorbate-80 (P 80) MNG PLGA NPs and examined the quantity of MNG through developed a novel method of LC–MS/MS in the ischemic rat brain treatment. The solvent evaporation method used to develop a novel MNG loaded PLGA NPs followed by their coating from polysorbate-80. Polysorbate-80 (P 80) MNG PLGA NPs developed based on EE, particle size, Zeta Potential, PDI, and loading capacity with their characterization followed by drug release and intranasal permeation to enhance the brain bioavailability and also determined their neurobehavioral as well as biochemical evaluation with the histopathological examination. P 80 MNG PLGA NPs were optimized with their particle size 103.4 ± 2.66 nm, PDI: 0.201 ± 0.008, Zeta Potential (−35.8 ± 2.48), and drug loading 37.16 ± 2.09% with 76.08 ± 4.91% entrapment efficiency showed a sustained and controlled release (83.43 ± 6.47%) with great permeation (> 83%) of MNG. MNG & IS showed retention time (0.756 and 1.258 min) and their m/z (421.20/301.20 and 237.2/179.2), respectively. MNG showed a good linearity range, i.e., 10.0–1000.0 ng mL−1; the results of inter-and-intraday accuracy and CV were found to be (93.01–99.43%) and (2.27–4.02%), respectively. An excellent significant results was showed, i.e., p < 0.001 for (AUC)0–24 & Cmax via i.n. dose delivered. A highly significantly results of P 80 MNG PLGA NPs (i.n.) were found based on the examination of biochemical, neurobehavioral, and histopathological in the developed ischemic MCAO brain rat’s model. An excellent significant role of P 80 MNG PLGA NPs for MNG were proved based on enhancement of brain bioavailability of MNG via i.n. delivery of the rats and targeted easily to the brain in the treatment of cerebral ischemia followed by improvement of neuroprotection based on use of a very small dose of MNG.

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Abbreviations

MNG:

Mangiferin

P 80:

Polysorbate-80

PLGA:

Poly (lactic-co-glycolic acid)

NPs:

Nanoparticles

LC–MS/MS:

Liquid chromatography-mass spectrometry/mass spectrometry

EE:

Entrapment/encapsulation efficiency

PDI:

Polydispersity index

ZP:

Zeta Potential

CV:

Coefficient of variation

AUC:

Area under curve

i.v.:

Intravenous

i.n.:

Intranasal

MCAO:

Middle cerebral artery occlusion

LOQQC:

Lower limit of quantification of quality control

LQC:

Lower-level quality control

MQC:

Middle level quality control

HQC:

Higher level quality control

RT:

Retention time

ROS:

Reactive oxygen species

DCM:

Dichloromethane

SEM:

Scanning electron microscopy

DSC:

Differential scanning calorimetry

TDDS:

Targeted drug delivery system

PK:

Pharmacokinetic

SMA:

Spontaneous motor activity

FT:

Flexion test

GPx:

Glutathione peroxidase

CAT:

Catalase

SOD:

Superoxide dismutase

GR:

Glutathione reductase

TBARS:

Thiobarbituric acid reactive substances

K el :

Elimination rate cinstatnt

t 1/2 :

Half-life

C max :

The maximum (or peak) serum/plasma/brain concentration

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Funding

Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia have supported financially to conduct this study (PSAU/2023/R/1444).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Green Research Lab, Riyadh, Kingdom of Saudi Arabia

    Niyaz Ahmad

  2. Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441, Dammam, Kingdom of Saudi Arabia

    Niyaz Ahmad

  3. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India

    Niyaz Ahmad

  4. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia

    Mohd Faiyaz Khan

  5. Department of Pharmaceutical Sciences, College of Pharmacy and Dentistry, Buraydah Colleges, Buraydah, Al-Qassim, Kingdom of Saudi Arabia

    Zabih Ullah

  6. Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom of Saudi Arabia

    Anis Ahmad Chaudhary & Abdullah S. Alawam

  7. Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia

    Mohammed Saifuddin Khalid & Mohammed Taher Ali

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  1. Niyaz Ahmad
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Ahmad, N., Khan, M.F., Ullah, Z. et al. Development and evaluation of polysorbate-80 coated Mangiferin PLGA nanoparticles used in the treatment of cerebral ischemia. Polym. Bull. 81, 7035–7069 (2024). https://doi.org/10.1007/s00289-023-05030-x

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