Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate

Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate Publisher Pubmed

Rezaie Shirmard L¹ ; Ghofrani M² ; Bahari Javan N² ; Bayrami S² ; Tavassoli A³ ; Rezaie A⁴ ; Amini M^{5, 6} ; Kebriaeezadeh A⁷ ; Rouini MR⁸ ; Dinarvand R² ; Rafieetehrani M² ; Dorkoosh FA^{2, 9}

Show Affiliations

1. Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
2. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Analytical chemistry, University of Mazandaran, Babolsar, Iran
4. School of Dentistry, Ardabil University of Medical Sciences, Ardabil, Iran
5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
6. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Pharmacoeconomy and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
8. Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, University of Medical Sciences, Tehran, Iran
9. Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran

Source: Drug Development and Industrial Pharmacy Published:2020

Abstract

Uncontrolled distribution of nanoparticles (NPs) within the body can significantly decrease the efficiency of drug therapy and is considered among the main restrictions of NPs application. The aim of this study was to develop a depot combination delivery system (CDS) containing fingolimod loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) NPs dispersed into a matrix of oleic acid-grafted-aminated alginate (OA-g-AAlg) to minimize the nonspecific biodistribution (BD) of PHBV NPs. OA-g-AAlg was synthesized in two step; First, Alg was aminated by using adipic dihydrazide (ADH). The degree of hyrazide group substitution of Alg was determined by trinitro-benzene-sulfonic acid (TNBS) assay. Second, OA was attached to AAlg through formation of an amide bond. Chemical structure of OA-g-AAlg was confirmed with FTIR and HNMR spectroscopy. Furthermore, rheological properties of OA-g-AAlg with different grafting ratios were evaluated. In-vitro release studies indicated that 47% of fingolimod was released from the CDS within 28 days. Blood and tissue samples were analyzed using liquid chromatography/tandem mass spectrometry following subcutaneous (SC) injection of fingolimod-CDS into Wistar rats. The elimination phase half-life of CDS-fingolimod was significantly higher than that of fingolimod (∼32 d vs. ∼20 h). To investigate the therapeutic efficacy, lymphocyte count was assessed over a 40 day period in Wistar rats. Peripheral blood lymphocyte count decreased from baseline by 27 ± 8% in 2 days after injection. Overall, the designed CDS represented promising results in improving the pharmacokinetic properties of fingolimod. Therefore, we believe that this sustained release formulation has a great potential to be applied to delivery of various therapeutics. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

2. Preparation, Statistical Optimisation and in Vitro Characterisation of Poly (3-Hydroxybutyrate-Co-3-Hydroxyvalerate)/Poly (Lactic-Co-Glycolic Acid) Blend Nanoparticles for Prolonged Delivery of Teriparatide, Journal of Microencapsulation (2016)

3. Nanoparticulate Fingolimod Delivery System Based on Biodegradable Poly (3-Hydroxybutyrate-Co-3-Hydroxyvalerate) (Phbv): Design, Optimization, Characterization and In-Vitro Evaluation, Pharmaceutical Development and Technology (2017)

4. Preparation and in Vitro Release Profiling of Plga Microspheres Containing Bsa As a Model Protein, Brazilian Journal of Pharmaceutical Sciences (2020)

5. Bmj Open Effect of Fty720 (Fingolimod) on Graft Survival in Renal Transplant Recipients: A Systematic Review Protocol, BMJ Open (2016)

6. Prolonged Injectable Formulation of Nafarelin Using in Situ Gel Combination Delivery System, Pharmaceutical Development and Technology (2018)

7. Clinical Applications of Nanomedicine in Cancer Therapy, Drug Discovery Today (2020)

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Farid Dorkoosh (4)

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Style	Citing Format
MLA	Rezaie Shirmard L, et al.. "Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate." Drug Development and Industrial Pharmacy, vol. 46, no. 2, 2020, pp. 318-328.
APA	Rezaie Shirmard L, Ghofrani M, Bahari Javan N, Bayrami S, Tavassoli A, Rezaie A, Amini M, Kebriaeezadeh A, Rouini MR, Dinarvand R, Rafieetehrani M, Dorkoosh FA (2020). Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate. Drug Development and Industrial Pharmacy, 46(2), 318-328.
Chicago	Rezaie Shirmard L, Ghofrani M, Bahari Javan N, Bayrami S, Tavassoli A, Rezaie A, Amini M, et al.. "Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate." Drug Development and Industrial Pharmacy 46, no. 2 (2020): 318-328.
Harvard	Rezaie Shirmard L et al. (2020) 'Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate', Drug Development and Industrial Pharmacy, 46(2), pp. 318-328.
Vancouver	Rezaie Shirmard L, Ghofrani M, Bahari Javan N, Bayrami S, Tavassoli A, Rezaie A, et al.. Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate. Drug Development and Industrial Pharmacy. 2020;46(2):318-328.
BibTex	@article{ author = {Rezaie Shirmard L and Ghofrani M and Bahari Javan N and Bayrami S and Tavassoli A and Rezaie A and Amini M and Kebriaeezadeh A and Rouini MR and Dinarvand R and Rafieetehrani M and Dorkoosh FA}, title = {Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate}, journal = {Drug Development and Industrial Pharmacy}, volume = {46}, number = {2}, pages = {318-328}, year = {2020} }
RIS	TY - JOUR AU - Rezaie Shirmard L AU - Ghofrani M AU - Bahari Javan N AU - Bayrami S AU - Tavassoli A AU - Rezaie A AU - Amini M AU - Kebriaeezadeh A AU - Rouini MR AU - Dinarvand R AU - Rafieetehrani M AU - Dorkoosh FA TI - Improving the In-Vivo Biological Activity of Fingolimod Loaded Phbv Nanoparticles by Using Hydrophobically Modified Alginate JO - Drug Development and Industrial Pharmacy VL - 46 IS - 2 SP - 318 EP - 328 PY - 2020 ER -

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