PMID- 32504798 OWN - NLM STAT- MEDLINE DCOM- 20210209 LR - 20210209 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 153 DP - 2020 Aug TI - Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats. PG - 1-13 LID - S0939-6411(20)30157-0 [pii] LID - 10.1016/j.ejpb.2020.05.032 [doi] AB - Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm(2). Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Haidar, Mohammad Karim AU - Haidar MK AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Erzincan Binali Yildirim University, 24100 Erzincan, Turkey. FAU - Timur, Selin Seda AU - Timur SS AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. FAU - Kazanci, Atilla AU - Kazanci A AD - Department of Neurosurgery Faculty of Medicine, Ankara Yildirim Beyazit University, 06810 Ankara, Turkey. FAU - Turkoglu, Omer Faruk AU - Turkoglu OF AD - Department of Neurosurgery, City Hospital, Turkish Republic Ministry of Health, 06810 Ankara, Turkey. FAU - Gursoy, R Neslihan AU - Gursoy RN AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. FAU - Nemutlu, Emirhan AU - Nemutlu E AD - Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. FAU - Sargon, Mustafa Fevzi AU - Sargon MF AD - Department of Anatomy, School of Medicine, Atilim University, 06830 Ankara, Turkey. FAU - Bodur, Ebru AU - Bodur E AD - Department of Biochemistry, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey. FAU - Gok, Muslum AU - Gok M AD - Department of Biochemistry, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey. FAU - Ulubayram, Kezban AU - Ulubayram K AD - Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University 06100 Ankara, Turkey. FAU - Oner, Levent AU - Oner L AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. FAU - Eroglu, Hakan AU - Eroglu H AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: ehakan@hacettepe.edu.tr. LA - eng PT - Journal Article DEP - 20200603 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 0 (Neuroprotective Agents) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 73Y7P0K73Y (Thioctic Acid) RN - A0JWA85V8F (Atorvastatin) SB - IM MH - Animals MH - Atorvastatin/*chemistry/*pharmacology MH - Mice MH - Nanofibers/*chemistry MH - Nerve Regeneration/drug effects MH - Neuroprotection/drug effects MH - Neuroprotective Agents/*chemistry/*pharmacology MH - Peripheral Nerve Injuries/*drug therapy MH - Polyethylene Glycols/chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/drug effects MH - Sciatic Nerve/drug effects MH - Sciatic Neuropathy/drug therapy MH - Thioctic Acid/*chemistry OTO - NOTNLM OT - Alpha lipoic acid OT - Atorvastatin OT - Composite nanofibers OT - Neuroprotection OT - Peripheral nerve injury EDAT- 2020/06/07 06:00 MHDA- 2021/02/10 06:00 CRDT- 2020/06/07 06:00 PHST- 2020/04/05 00:00 [received] PHST- 2020/05/25 00:00 [revised] PHST- 2020/05/31 00:00 [accepted] PHST- 2020/06/07 06:00 [pubmed] PHST- 2021/02/10 06:00 [medline] PHST- 2020/06/07 06:00 [entrez] AID - S0939-6411(20)30157-0 [pii] AID - 10.1016/j.ejpb.2020.05.032 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2020 Aug;153:1-13. doi: 10.1016/j.ejpb.2020.05.032. Epub 2020 Jun 3.