title

بهبود عملکرد بیولوژیکی فینگولیمود بارگزاری شده در نانوپارتیکلهای پلی هیدروکسی بوتیرات والرات با استفاده از مشتقات لیوفیل آلژینات سدیم

رضایی شیرمرد, لیلا and غفرانی, مهدیه and بهاری جوان, نیکا and بایرامی, سمانه and توسلی, عبدالله and رضایی, امیر and امینی, محسن and کبریایی زاده, عباس and رویینی, محمدرضا and دیناروند, رسول and رفیعی تهرانی, مرتضی and درکوش, فرید (1399) بهبود عملکرد بیولوژیکی فینگولیمود بارگزاری شده در نانوپارتیکلهای پلی هیدروکسی بوتیرات والرات با استفاده از مشتقات لیوفیل آلژینات سدیم. Drug Development and Industrial Pharmacy ــ 46 (2). pp. 318-328. شاپا 0363-9045

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Title

Improving the in-vivo biological activity of fingolimod loaded PHBV nanoparticles by using hydrophobically modified alginate

English 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.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :لیلا رضایی شیرمرد
نویسنده :مهدیه غفرانی
نویسنده :نیکا بهاری جوان
نویسنده :سمانه بایرامی
نویسنده :عبدالله توسلی
نویسنده :امیر رضایی
نویسنده :محسن امینی
نویسنده :عباس کبریایی زاده
نویسنده :محمدرضا رویینی
نویسنده :رسول دیناروند
نویسنده :مرتضی رفیعی تهرانی
نویسنده مسئول :فرید درکوش
Additional Information:IF: 2.367 Indexed in: ISI, Scopus, PubMed, Embase
Uncontrolled Keywords:دارورسانی ترکیبی، نانوپارتیکل، آلژینات، دارورسانی آهسته رهش، فینگولیمود
کلیدواژه ها (انگلیسی):Combination Delivery System, PHBV Nanoparticles, Alginate, Prolonged release, fingolimod
Subjects:QV pharmacology > QV 704 Pharmaceutics
Divisions:School of Pharmacy > Department of Pharmaceutics
ID Code:13905
Deposited By: Dr Leila Rezaie Shirmard
Deposited On:05 Nov 1399 12:45
Last Modified:05 Nov 1399 12:45

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