PMID- 30041028 OWN - NLM STAT- MEDLINE DCOM- 20190726 LR - 20190726 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 123 DP - 2018 Oct 15 TI - Influence of controlled release of resveratrol from electrospun fibers in combination with siRNA on leukemia cells. PG - 173-183 LID - S0928-0987(18)30341-5 [pii] LID - 10.1016/j.ejps.2018.07.043 [doi] AB - In this study, we evaluated the possibility of i) local release of resveratrol from poly(epsilon-caprolactone) (PCL) and gelatin (GT) electrospun fibers and ii) combining (i) with siRNA designed to downregulate BCR-ABL pathway on K562 cancer cells. Initially, K562 cell culture experiments were performed using various bolus doses of resveratrol in combination with siRNA for 3 days using a factorial design of experiments approach. Resveratrol content was analyzed using HPLC and cell viability was assessed using Annexin V (Non-viable), and Propidium Iodide (PI) (Necrotic) based flow cytometry. Coaxial electrospun fibers with resveratrol were made using 1:1 PCL-GT blends in different configurations: single fibers and coaxial fibers with same polymer blends, or with PCL inner core. Loading efficiency and release profile over five days were analyzed. Based on release profile, K562 cell viability with fibers was analyzed over eight days. Dose dependent cell death was observed with bolus resveratrol and siRNA in the culture. However, resveratrol content depleted significantly when added directly to solution. The combination therapy was additive in solution. SEM analysis showed no phase separation of components and resveratrol loading efficiency varied from 77% to 88% in different configurations; 95% of resveratrol was released by day five. Permeability of resveratrol showed no significant dependency on fiber configuration. After 8 days, non-viable cell percentages with controlled release were similar to that at three-day bolus dose of resveratrol. However, siRNA interacted with the fibers, resulting in reduced effect on cells. Loading resveratrol into electrospun fibers provides a localized delivery at therapeutic level, and increased resveratrol's apoptotic effect. Using single fibers is sufficient for controlled release. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Al-Attar, Thikrayat AU - Al-Attar T AD - School of Chemical Engineering, Oklahoma State University, 420 Engineering North, Stillwater, OK 74078, United States of America. Electronic address: tina.al-attar@okstate.edu. FAU - Madihally, Sundararajan V AU - Madihally SV AD - School of Chemical Engineering, Oklahoma State University, 420 Engineering North, Stillwater, OK 74078, United States of America. Electronic address: sundar.madihally@okstate.edu. LA - eng PT - Journal Article DEP - 20180721 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 0 (Drug Carriers) RN - 0 (Polyesters) RN - 0 (RNA, Small Interfering) RN - 24980-41-4 (polycaprolactone) RN - 9000-70-8 (Gelatin) RN - Q369O8926L (Resveratrol) MH - *Drug Carriers MH - Drug Liberation MH - Gelatin/chemistry MH - Humans MH - K562 Cells MH - Leukemia/*drug therapy MH - *Nanofibers MH - Polyesters/chemistry MH - RNA, Small Interfering/*pharmacology MH - Resveratrol/*pharmacology OTO - NOTNLM OT - Apoptosis OT - Electrospinning OT - Leukemia OT - Permeability OT - Polymers OT - Resveratrol OT - siRNA EDAT- 2018/07/25 06:00 MHDA- 2019/07/28 06:00 CRDT- 2018/07/25 06:00 PHST- 2018/03/22 00:00 [received] PHST- 2018/05/23 00:00 [revised] PHST- 2018/07/20 00:00 [accepted] PHST- 2018/07/25 06:00 [pubmed] PHST- 2019/07/28 06:00 [medline] PHST- 2018/07/25 06:00 [entrez] AID - S0928-0987(18)30341-5 [pii] AID - 10.1016/j.ejps.2018.07.043 [doi] PST - ppublish SO - Eur J Pharm Sci. 2018 Oct 15;123:173-183. doi: 10.1016/j.ejps.2018.07.043. Epub 2018 Jul 21.