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

Kim SR, Ho MJ, Lee E, Lee JW, Choi YW, Kang MJ - Int J Nanomedicine (2015)

Bottom Line: Hyperspectral imaging (CytoViva(®)) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 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.

No MeSH data available.


Representative in vivo fluorescence images of (A) DiR-loaded cationic NPs and (B) free DiR solution after IA injection in mice knee at various time points. Notes: The scale bar range is (A) 0.5–2×108 and (B) 0.5–1.5×108 in fluorescence intensity.Abbreviations: DiR, 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide; NP, nanoparticle; IA, intra-articular.
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f5-ijn-10-5263: Representative in vivo fluorescence images of (A) DiR-loaded cationic NPs and (B) free DiR solution after IA injection in mice knee at various time points. Notes: The scale bar range is (A) 0.5–2×108 and (B) 0.5–1.5×108 in fluorescence intensity.Abbreviations: DiR, 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide; NP, nanoparticle; IA, intra-articular.

Mentions: The retention profile of the DiR-loaded cationic PLGA/Eudaragit RL NPs in the knee joint was investigated by fluorescence imaging after IA injection in mice. There were no abnormal clinical signs indicative of an adverse effect arising from the IA administration of either DiR-loaded NPs or DiR solution. Representative images for solution and cationic NPs after IA injection are shown in Figure 5. In addition, the relative fluorescent intensity profiles of cationic NPs versus a fluorescence probe solution are plotted in Figure 6. IA injection of the probe in solution displayed a rapid decline in fluorescence levels to 30% of the initial concentration within 3 days. The average half-life of the probe in the joint determined was approximately 22 hours, indicating the rapid efflux from the joint. The retention time of the probe in the joint was fairly longer than those of small molecules previously reported, due to its extreme hydrophobicity and high molecular weight (1,013 g/mol). The mean half-lives of the nonsteroidal anti-inflammatory agents such as paracetamol, salicylate, and diclofenac were 1.1, 2.4, and 5.2 hours, respectively, after IA injection in human patients with knee rheumatoid arthritis.37


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

Kim SR, Ho MJ, Lee E, Lee JW, Choi YW, Kang MJ - Int J Nanomedicine (2015)

Representative in vivo fluorescence images of (A) DiR-loaded cationic NPs and (B) free DiR solution after IA injection in mice knee at various time points. Notes: The scale bar range is (A) 0.5–2×108 and (B) 0.5–1.5×108 in fluorescence intensity.Abbreviations: DiR, 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide; NP, nanoparticle; IA, intra-articular.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554397&req=5

f5-ijn-10-5263: Representative in vivo fluorescence images of (A) DiR-loaded cationic NPs and (B) free DiR solution after IA injection in mice knee at various time points. Notes: The scale bar range is (A) 0.5–2×108 and (B) 0.5–1.5×108 in fluorescence intensity.Abbreviations: DiR, 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide; NP, nanoparticle; IA, intra-articular.
Mentions: The retention profile of the DiR-loaded cationic PLGA/Eudaragit RL NPs in the knee joint was investigated by fluorescence imaging after IA injection in mice. There were no abnormal clinical signs indicative of an adverse effect arising from the IA administration of either DiR-loaded NPs or DiR solution. Representative images for solution and cationic NPs after IA injection are shown in Figure 5. In addition, the relative fluorescent intensity profiles of cationic NPs versus a fluorescence probe solution are plotted in Figure 6. IA injection of the probe in solution displayed a rapid decline in fluorescence levels to 30% of the initial concentration within 3 days. The average half-life of the probe in the joint determined was approximately 22 hours, indicating the rapid efflux from the joint. The retention time of the probe in the joint was fairly longer than those of small molecules previously reported, due to its extreme hydrophobicity and high molecular weight (1,013 g/mol). The mean half-lives of the nonsteroidal anti-inflammatory agents such as paracetamol, salicylate, and diclofenac were 1.1, 2.4, and 5.2 hours, respectively, after IA injection in human patients with knee rheumatoid arthritis.37

Bottom Line: Hyperspectral imaging (CytoViva(®)) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides.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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 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.

No MeSH data available.