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A Comparative Study of Orally Delivered PBCA and ApoE Coupled BSA Nanoparticles for Brain Targeting of Sumatriptan Succinate in Therapeutic Management of Migraine

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ABSTRACT

Purpose

The present investigation aimed at brain targeting of sumatriptan succinate (SS) for its optimal therapeutic effect in migraine through nanoparticulate drug delivery system using poly (butyl cyanoacrylate) (PBCA) and bovine serum albumin linked with apolipoprotein E3 (BSA-ApoE).

Method

The study involved formulation optimization of PBCA nanoparticles (NPs) using central composite design for achieving minimum particle size, maximum entrapment efficiency along with sustained drug release. SS incorporated in BSA-ApoE NPs (S-AA-NP) were prepared by desolvation technique and compared with SS loaded polysorbate 80 coated optimized PBCA NPs (FPopt) in terms of their brain uptake potential, upon oral administration in male Wistar rats. The NPs were characterized by FTIR, thermal, powder XRD and TEM analysis.

Results

The in vivo studies of FPopt and S-AA-NP on male Wistar rats demonstrated a fairly high brain/plasma drug ratio of 9.45 and 12.67 respectively 2 h post oral drug administration. The behavioural studies on male Swiss albino mice affirmed the enhanced anti-migraine potential of S-AA-NP than FPopt (P < 0.001).

Conclusion

The results of this work, therefore, indicate that BSA-ApoE NPs are significantly better than polysorbate 80 coated PBCA NPs for brain targeting of SS (P < 0.05) and also offer an improved therapeutic strategy for migraine management.

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Abbreviations

AA-NP:

Dummy Apolipoprotein E coupled bovine serum albumin nanoparticles (without drug)

ApoE:

Apolipoprotein E

BBB:

Blood Brain Barrier

BSA:

Bovine Serum Albumin

BSA-ApoE:

Bovine Serum Albumin covalently linked with Apolipoprotein E

DSC:

Differential Scanning Calorimetry

FCopt :

Sumatriptan succinate loaded polysorbate 80 coated chitosan solid lipid nanoparticles

FPopt :

Sumatriptan succinate loaded polysorbate 80 coated optimized Poly (butyl cyanoacrylate) nanoparticles

FTIR:

Fourier-Transform Infrared Spectroscopy

HPLC:

High-Performance Liquid Chromatography

mmol:

Millimoles

nBCA:

n-Butyl-2-cyanoacrylate

NPs:

Nanoparticles

PBCA:

Poly (butyl cyanoacrylate) (PBCA)

pXRD:

Powder X-Ray Diffraction

S-AA-NP:

Sumatriptan succinate loaded apolipoprotein E coupled BSA nanoparticles

SLN:

Solid lipid nanoparticles

SS:

Sumatriptan Succinate

TEM:

Transmission Electron Microscopy

TGA:

Thermogravimetric analysis

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors acknowledge the Coordinator, DST FIST, Department of Pharmaceutical Sciences (GJU S&T, Hisar) and SAIF, Panjab University (Chandigarh) for providing particle size analysis and TEM analysis facility respectively. The authors are thankful to Department of Science & Technology, New Delhi for providing DST-INSPIRE fellowship as financial assistance. The contribution of Dr. Tikva Vogel in providing the gift sample of ApoE is gratefully acknowledged. The authors also wish to thank Dr. A.K. Mohanty, (Animal Biotechnology Centre, National Dairy Research Institute, Karnal, India) for kindly helping in the thiolation of apolipoprotein E. The authors report no conflict of interest and are solely responsible for the content and writing of the paper.

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  1. Department of Pharmaceutical Sciences, G. J. University of Sci. & Tech., Hisar, 125001, India

    Priti Girotra & Shailendra Kumar Singh

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  1. Priti Girotra
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  2. Shailendra Kumar Singh
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Correspondence to Shailendra Kumar Singh.

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Girotra, P., Singh, S.K. A Comparative Study of Orally Delivered PBCA and ApoE Coupled BSA Nanoparticles for Brain Targeting of Sumatriptan Succinate in Therapeutic Management of Migraine. Pharm Res 33, 1682–1695 (2016). https://doi.org/10.1007/s11095-016-1910-8

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