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Comparative evaluation of fish oil and butter oil in modulating delivery of galantamine hydrobromide to brain via intranasal route: pharmacokinetic and oxidative stress studies

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Abstract

The present study investigates the role of fish oil (FO)– and butter oil (BO)–enriched microemulsion-based system of galantamine hydrobromide (GH), an anti-Alzheimer drug, for its potential role in brain permeation enhancement and neuroprotection against oxidative stress. Microemulsion (ME)-based system of GH was prepared using water phase titration. The prepared ME was characterized by several physicochemical parameters like particle size, polydispersity index, and ex vivo drug permeation. Cell-based oxidative stress assays and pharmacokinetic studies were performed using C6 glial cell lines, and Sprague Dawley rats, respectively. The optimized ME comprised 5.3% v/v of Capmul MCM EP (as oil),15.8% v/v of Tween-80 (as surfactant), 5.3% v/v of Transcutol P (as co-surfactant), and 73.6% v/v of water (as aqueous phase). The addition of FO and BO resulted in a slight increase in the droplet size and decrease in transparency of ME. Cell-based anti-oxidative stress assays (glutathione assay, nitrite assay, and lipid peroxidation assay) showed the efficacy of formulation in the order of ME, BO ME, and FO ME, respectively. A similar trend was also observed in in vivo animal studies, wherein GH FO ME showed a comparatively higher percentage of drug reaching the brain when administered by intranasal route than by IV route. The study concluded the potential benefits of co-administering FO- and BO-enriched microemulsion is not only enhancing the permeation of drugs across BBB but also improving efficacy against lipopolysaccharide-induced oxidative stress.

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Abbreviations

AD:

Alzheimer’s disease

ANOVA:

analysis of variance

AUC:

area under curve

BACE 1:

beta-secretase 1

BBB:

blood-brain barrier

CNS:

central nervous system

DHA:

docosahexaenoic acid

DSC:

differential scanning calorimetry

DTNB:

5,5′-dithio-bis-[2-nitrobenzoic acid]

EPA:

eicosapentaenoic acid

FT-IR:

Fourier-transform infrared spectroscopy

GH:

galantamine hydrobromide

GH ME:

galantamine hydrobromide microemulsion

GH BO ME:

galantamine hydrobromide butter oil loaded microemulsion

GH FO ME:

galantamine hydrobromide fish oil loaded microemulsion

GSH:

glutathione

I.S:

internal standard

LC-MS:

liquid chromatography-mass spectrometry

LPS:

lipopolysaccharide

MDA:

malondialdehyde

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NADPH:

nicotinamide adenine dinucleotide phosphate

PDI:

polydispersity index

Q-TOF:

quadrupole-time-of-flight

ROS:

reactive oxygen species

RT:

room temperature

UV-VIS:

ultraviolet spectrophotometer

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Acknowledgments

All other authors are grateful to the Ministry of Chemicals and Fertilizer for providing fellowship. Authors would like to acknowledge Gattefosse (Mumbai, India) for gift samples of excipients.

Funding

The corresponding author would like to thank the Department of Science and Technology and SERB (INSPIRE Grant No: IFA-LSBM-13 and EMR/2016/007966/HS) for project funds.

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Authors and Affiliations

  1. Department of Pharmaceutics, NIPER-Ahmedabad, Palaj, Opp. Air force Station Headquarter, Gandhinagar, Gujarat, 382355, India

    Aakash Katdare, Dignesh Khunt, Shreya Thakkar, Surya Narayana Polaka & Manju Misra

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  1. Aakash Katdare
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  2. Dignesh Khunt
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  3. Shreya Thakkar
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  4. Surya Narayana Polaka
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  5. Manju Misra
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Corresponding author

Correspondence to Manju Misra.

Ethics declarations

The protocol for animal studies was approved by the Institutional Animal Ethics Committee (Approval No: NIPER A/IAEC/2018/006 under CPCSEA, Delhi, India), and studies were performed adhering to the guidelines at National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, India.

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The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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Katdare, A., Khunt, D., Thakkar, S. et al. Comparative evaluation of fish oil and butter oil in modulating delivery of galantamine hydrobromide to brain via intranasal route: pharmacokinetic and oxidative stress studies. Drug Deliv. and Transl. Res. 10, 1136–1146 (2020). https://doi.org/10.1007/s13346-020-00739-y

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