Improving the in-vivo biological activity of fingolimod loaded PHBV nanoparticles by using hydrophobically modified alginate. (1st February 2020)

• Record Type: Journal Article
• Authors: Rezaie Shirmard, Leila; Ghofrani, Mahdieh; Bahari Javan, Nika; Bayrami, Samane; Tavassoli, Abdollah; Rezaie, Amir; Amini, Mohsen; Kebriaee-zadeh, Abbas; Rouini, Mohammad-Reza; Dinarvand, Rassoul; Rafiee-Tehrani, Morteza; Dorkoosh, Farid Abedin
• Is Part Of: Drug development and industrial pharmacy. Volume 46:Number 2(2020)
• Page Start: 318
• Page End: 328
• Publication Date: 2020-02-01
• Subjects: Combination delivery system -- PHBV nanoparticles -- alginate -- prolonged release -- fingolimod; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2020.1721524
• Languages: English
• ISSNs: 0363-9045

Abstract

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.