PMID- 31976771
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20201116
IS  - 1520-5762 (Electronic)
IS  - 0363-9045 (Linking)
VI  - 46
IP  - 2
DP  - 2020 Feb
TI  - Improving the in-vivo biological activity of fingolimod loaded PHBV nanoparticles 
      by using hydrophobically modified alginate.
PG  - 318-328
LID - 10.1080/03639045.2020.1721524 [doi]
AB  - 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 ( approximately 32 d vs. 
       approximately 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.
FAU - Rezaie Shirmard, Leila
AU  - Rezaie Shirmard L
AD  - Department of Pharmaceutics, School of Pharmacy, Ardabil University of Medical 
      Sciences, Ardabil, Iran.
FAU - Ghofrani, Mahdieh
AU  - Ghofrani M
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Bahari Javan, Nika
AU  - Bahari Javan N
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Bayrami, Samane
AU  - Bayrami S
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Tavassoli, Abdollah
AU  - Tavassoli A
AD  - Department of Analytical chemistry, University of Mazandaran, Babolsar, Iran.
FAU - Rezaie, Amir
AU  - Rezaie A
AD  - School of Dentistry, Ardabil University of Medical Sciences, Ardabil, Iran.
FAU - Amini, Mohsen
AU  - Amini M
AD  - Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of 
      Medical Sciences, Tehran, Iran.
AD  - Drug Design and Development Research Center, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Kebriaee-Zadeh, Abbas
AU  - Kebriaee-Zadeh A
AD  - Department of Pharmacoeconomy and Pharmaceutical Administration, Faculty of 
      Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
FAU - Rouini, Mohammad-Reza
AU  - Rouini MR
AD  - Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, 
      Faculty of Pharmacy, University of Medical Sciences, Tehran, Iran.
FAU - Dinarvand, Rassoul
AU  - Dinarvand R
AUID- ORCID: 0000-0003-0694-7556
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Rafiee-Tehrani, Morteza
AU  - Rafiee-Tehrani M
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Dorkoosh, Farid Abedin
AU  - Dorkoosh FA
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical 
      Sciences, Tehran, Iran.
AD  - Medical Biomaterial Research Centre (MBRC), Tehran University of Medical 
      Sciences, Tehran, Iran.
LA  - eng
PT  - Journal Article
DEP - 20200206
PL  - England
TA  - Drug Dev Ind Pharm
JT  - Drug development and industrial pharmacy
JID - 7802620
RN  - 0 (Alginates)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Carriers)
RN  - 0 (Polyesters)
RN  - 0 (poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate))
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Alginates/*chemistry
MH  - Animals
MH  - Delayed-Action Preparations/chemistry/pharmacokinetics/pharmacology
MH  - Drug Carriers/chemistry
MH  - Drug Delivery Systems/methods
MH  - Fingolimod Hydrochloride/*chemistry/pharmacokinetics/pharmacology
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Male
MH  - Nanoparticles/*chemistry
MH  - Polyesters/*chemistry
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Combination delivery system
OT  - PHBV nanoparticles
OT  - alginate
OT  - fingolimod
OT  - prolonged release
EDAT- 2020/01/25 06:00
MHDA- 2020/11/18 06:00
CRDT- 2020/01/25 06:00
PHST- 2020/01/25 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/01/25 06:00 [entrez]
AID - 10.1080/03639045.2020.1721524 [doi]
PST - ppublish
SO  - Drug Dev Ind Pharm. 2020 Feb;46(2):318-328. doi: 10.1080/03639045.2020.1721524. 
      Epub 2020 Feb 6.