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Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

Authors Kim SR, Ho MJ, Lee E, Lee JW, Choi YW, Kang MJ

Received 11 May 2015

Accepted for publication 8 July 2015

Published 24 August 2015 Volume 2015:10(1) Pages 5263—5271

DOI https://doi.org/10.2147/IJN.S88363

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Thomas J Webster

Sung Rae Kim,1 Myoung Jin Ho,2 Eugene Lee,3 Joon Woo Lee,3 Young Wook Choi,1 Myung Joo Kang2

1
College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 2College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, 3Department of Radiology, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Gyeonggi-do, South Korea

Abstract: Positively surface-charged poly(lactide-co-glycolide) (PLGA)/Eudragit RL nanoparticles (NPs) were designed to increase retention time and sustain release profile in joints after intra-articular injection, by forming micrometer-sized electrostatic aggregates with hyaluronic acid, an endogenous anionic polysaccharide found in high amounts in synovial fluid. The cationic NPs consisting of PLGA, Eudragit RL, and polyvinyl alcohol were fabricated by solvent evaporation technique. The NPs were 170.1 nm in size, with a zeta potential of 21.3 mV in phosphate-buffered saline. Hyperspectral imaging (CytoViva®) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides. NPs loaded with a fluorescent probe (1,1'-dioctadecyl-3,3,3',3' tetramethylindotricarbocyanine iodide, DiR) displayed a significantly improved retention time in the knee joint, with over 50% preservation of the fluorescent signal 28 days after injection. When DiR solution was injected intra-articularly, the fluorescence levels rapidly decreased to 30% of the initial concentration within 3 days in mice. From these findings, we suggest that PLGA-based cationic NPs could be a promising tool for prolonged delivery of therapeutic agents in joints selectively.

Keywords: PLGA, Eudragit RL, hyaluronic acid, cationic nanoparticles, intra-articular injection, electrostatic interaction

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