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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.


Related in: MedlinePlus

In vitro release of the fluorescent probe from the cationic NPs and NPs/HAs aggregates in 10 mM PBS with 1% (w/v) SLS at 37°C.Note: Vertical bars represent mean ± SD (n=3).Abbreviations: NP, nanoparticle; HA, hyaluronic acid; PBS, phosphate-buffered saline; SLS, sodium lauryl sulfate; SD, standard deviation.
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f4-ijn-10-5263: In vitro release of the fluorescent probe from the cationic NPs and NPs/HAs aggregates in 10 mM PBS with 1% (w/v) SLS at 37°C.Note: Vertical bars represent mean ± SD (n=3).Abbreviations: NP, nanoparticle; HA, hyaluronic acid; PBS, phosphate-buffered saline; SLS, sodium lauryl sulfate; SD, standard deviation.

Mentions: Hyperspectral imaging was further utilized to investigate the morphology of the cationic NP/HA aggregates and the distribution of DiR-loaded NPs in these aggregates (Figure 3). The concentration of HA in aqueous medium was set to 2.0 mg/mL because the concentration of HA in synovial fluid was reduced from 3.5 to below 2.2 mg/mL in osteoarthritic conditions.30Figure 4A displays representative optical micrographs of the filamentous NP/HA aggregates. Immediately upon mixing DiR-loaded NPs with HA under gentle agitation, discontinuous and filamentous aggregates ranging in diameter from 5 to 50 μm were precipitated without additional treatment (Figure 3A). DiR-loaded NPs were visualized in red using HyperVisual Software (Exelis Visual Information Solutions) to determine the distribution of NPs in the aggregates (Figure 3B). From the merged image of Figure 3A and B, we see that DiR-loaded NPs are localized homogeneously on the surface and/or inside of the aggregates (Figure 3C), which indicates that the electrostatic interaction of the cationic PLGA NP with the anionic polymer could be attributed to the formation of ionically cross-linked clusters. From these data, we expected that the construction of micrometer-sized NP/HA structures in synovial cavity restrict diffusion through the interstitium and across capillary walls in joints after IA injection of NP suspension. Also, the steric hindrance effect of the endogenous HA polysaccharides around the surface of the NP would help to avoid uptake by the reticuloendothelial system, thereby prolonging the retention of NP in the joint tissue. Mizrahy et al35 reported that the attachment of HA ranging from 6.4 to 1,500 kDa on the NP surface acts as a steric barrier to reduce clearance of the NPs by macrophages in the liver and promotes enhanced permeation and retention.


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)

In vitro release of the fluorescent probe from the cationic NPs and NPs/HAs aggregates in 10 mM PBS with 1% (w/v) SLS at 37°C.Note: Vertical bars represent mean ± SD (n=3).Abbreviations: NP, nanoparticle; HA, hyaluronic acid; PBS, phosphate-buffered saline; SLS, sodium lauryl sulfate; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-5263: In vitro release of the fluorescent probe from the cationic NPs and NPs/HAs aggregates in 10 mM PBS with 1% (w/v) SLS at 37°C.Note: Vertical bars represent mean ± SD (n=3).Abbreviations: NP, nanoparticle; HA, hyaluronic acid; PBS, phosphate-buffered saline; SLS, sodium lauryl sulfate; SD, standard deviation.
Mentions: Hyperspectral imaging was further utilized to investigate the morphology of the cationic NP/HA aggregates and the distribution of DiR-loaded NPs in these aggregates (Figure 3). The concentration of HA in aqueous medium was set to 2.0 mg/mL because the concentration of HA in synovial fluid was reduced from 3.5 to below 2.2 mg/mL in osteoarthritic conditions.30Figure 4A displays representative optical micrographs of the filamentous NP/HA aggregates. Immediately upon mixing DiR-loaded NPs with HA under gentle agitation, discontinuous and filamentous aggregates ranging in diameter from 5 to 50 μm were precipitated without additional treatment (Figure 3A). DiR-loaded NPs were visualized in red using HyperVisual Software (Exelis Visual Information Solutions) to determine the distribution of NPs in the aggregates (Figure 3B). From the merged image of Figure 3A and B, we see that DiR-loaded NPs are localized homogeneously on the surface and/or inside of the aggregates (Figure 3C), which indicates that the electrostatic interaction of the cationic PLGA NP with the anionic polymer could be attributed to the formation of ionically cross-linked clusters. From these data, we expected that the construction of micrometer-sized NP/HA structures in synovial cavity restrict diffusion through the interstitium and across capillary walls in joints after IA injection of NP suspension. Also, the steric hindrance effect of the endogenous HA polysaccharides around the surface of the NP would help to avoid uptake by the reticuloendothelial system, thereby prolonging the retention of NP in the joint tissue. Mizrahy et al35 reported that the attachment of HA ranging from 6.4 to 1,500 kDa on the NP surface acts as a steric barrier to reduce clearance of the NPs by macrophages in the liver and promotes enhanced permeation and retention.

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.


Related in: MedlinePlus