Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint.
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.
College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, South Korea.
Sung Rae
SR
Kim
College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, South Korea.
Myoung Jin
MJ
Ho
Department of Radiology, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Gyeonggi-do, South Korea.
Eugene
E
Lee
Department of Radiology, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Gyeonggi-do, South Korea.
Joon Woo
JW
Lee
College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, South Korea.
Young Wook
YW
Choi
College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, South Korea.
Myung Joo
MJ
Kang
D000818:Animals; D002412:Cations / Q000737:chemistry; D005456:Fluorescent Dyes; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D055672:Static Electricity; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000187:drug effects
D002412:Cations; D005456:Fluorescent Dyes; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; C058665:Eudragit RL; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid
Eudragit RL; PLGA; cationic nanoparticles; electrostatic interaction; hyaluronic acid; intra-articular injection