A Comparative Study of Orally Delivered PBCA and ApoE Coupled BSA Nanoparticles for Brain Targeting of Sumatriptan Succinate in Therapeutic Management of Migraine
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).
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.
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).
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.
KEY WORDSapolipoprotein brain targeting BSA PBCA sumatriptan succinate
Dummy Apolipoprotein E coupled bovine serum albumin nanoparticles (without drug)
Blood Brain Barrier
Bovine Serum Albumin
Bovine Serum Albumin covalently linked with Apolipoprotein E
Differential Scanning Calorimetry
Sumatriptan succinate loaded polysorbate 80 coated chitosan solid lipid nanoparticles
Sumatriptan succinate loaded polysorbate 80 coated optimized Poly (butyl cyanoacrylate) nanoparticles
Fourier-Transform Infrared Spectroscopy
High-Performance Liquid Chromatography
Poly (butyl cyanoacrylate) (PBCA)
Powder X-Ray Diffraction
Sumatriptan succinate loaded apolipoprotein E coupled BSA nanoparticles
Solid lipid nanoparticles
Transmission Electron Microscopy
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.
- 8.Alonso MJ, Csaba NS. Nanostructured biomaterials for overcoming biological barriers. RSC Publishing; 2012.Google Scholar
- 9.Gao S, Xu Y, Asghar S, Chen M, Zou L, Eltayeb S, et al. Poly butylcyanoacrylate nanocarriers as promising targeted drug delivery systems. J Drug Target. 2015;4:1–16.Google Scholar
- 15.Alyautdin R, Gothier D, Petrov V, Kharkevich D, Kreuter J. Analgesic activity of the hexapeptide dalargin adsorbed on the surface of polysorbate 80-coated poly (butyl cyanoacrylate) nanoparticles. Eur J Pharm Biopharm. 1995;41:44–8.Google Scholar
- 20.Wu LS. Product testing with consumers for research guidance. ASTM Int. 1989;1035:48–50.Google Scholar
- 26.Girotra PH, Singh SK, Kumar G. Reversed phase HPLC method development and validation for the quantification of sumatriptan succinate nanoparticles in rat plasma and brain homogenate. Inventi Impact: Biomed Anal. 2016;1:1–5.Google Scholar