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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.


Effect of formulation variables on size distribution and surface charge of PLGA/Eudragit RL NPs.Notes: Influence of (A) PVA concentration and (B) organic phase and aqueous phase ratio on the particle diameter and surface charge of PLGA/Eudragit RL (50:50) NPs. Influence of PLGA and Eudragit RL ratio on particle size and surface charge with (C) 0.1% PVA and (D) 1.0% PVA aqueous phase.Abbreviations: PLGA, poly(lactide-co-glycolide); NP, nanoparticle; PVA, polyvinyl alcohol.
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f1-ijn-10-5263: Effect of formulation variables on size distribution and surface charge of PLGA/Eudragit RL NPs.Notes: Influence of (A) PVA concentration and (B) organic phase and aqueous phase ratio on the particle diameter and surface charge of PLGA/Eudragit RL (50:50) NPs. Influence of PLGA and Eudragit RL ratio on particle size and surface charge with (C) 0.1% PVA and (D) 1.0% PVA aqueous phase.Abbreviations: PLGA, poly(lactide-co-glycolide); NP, nanoparticle; PVA, polyvinyl alcohol.

Mentions: The particle preparation process was studied by assessing PVA concentration in external phase, PLGA and Eudragit RL ratios, and phase ratio to clarify the influence of these factors on particle size and surface charge of blank NPs (Figure 1). The effect of PVA content on the physical properties of the PLGA/Eudragit RL (50:50) NPs is shown in Figure 1A. There was a decrease in particle size from 250 to 150 nm when the PVA concentration in the external aqueous phase was increased from 0% to 1% (w/v). On the other hand, the surface charge of the NPs was rapidly decreased and neutralized with PVA concentration above 0.3%. The internal/external phase ratio did not significantly influence the droplet size and zeta potential of PLGA/Eudragit RL (50:50) NPs (Figure 1B). The effect of PLGA and Eudragit RL ratio was further investigated, and the results are shown in Figure 1C and D. In the PLGA/Eudragit RL NPs with 0.1% PVA, as the proportion of the cationic polymer was increased, surface charge of NPs increased and they reached a plateau at 10% Eudragit RL, with a particle size below 200 nm (Figure 1C). However, in the case of the NPs with 1.0% PVA, the particle size was affixed to 140–180 nm with a neutral surface charge, regardless of PLGA/Eudragit RL ratio (Figure 1D). Therefore, the PLGA/Eudragit RL ratio was determined to weight ratio of 70:30, and the PVA concentration in external phase was determined to 0.1% to formulate positively surface-charged NPs. This optimized NP composition provides appropriate particle size below 200 nm, with a surface potential of over 20 mV, and was used for further in vitro and in vivo studies.


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)

Effect of formulation variables on size distribution and surface charge of PLGA/Eudragit RL NPs.Notes: Influence of (A) PVA concentration and (B) organic phase and aqueous phase ratio on the particle diameter and surface charge of PLGA/Eudragit RL (50:50) NPs. Influence of PLGA and Eudragit RL ratio on particle size and surface charge with (C) 0.1% PVA and (D) 1.0% PVA aqueous phase.Abbreviations: PLGA, poly(lactide-co-glycolide); NP, nanoparticle; PVA, polyvinyl alcohol.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-5263: Effect of formulation variables on size distribution and surface charge of PLGA/Eudragit RL NPs.Notes: Influence of (A) PVA concentration and (B) organic phase and aqueous phase ratio on the particle diameter and surface charge of PLGA/Eudragit RL (50:50) NPs. Influence of PLGA and Eudragit RL ratio on particle size and surface charge with (C) 0.1% PVA and (D) 1.0% PVA aqueous phase.Abbreviations: PLGA, poly(lactide-co-glycolide); NP, nanoparticle; PVA, polyvinyl alcohol.
Mentions: The particle preparation process was studied by assessing PVA concentration in external phase, PLGA and Eudragit RL ratios, and phase ratio to clarify the influence of these factors on particle size and surface charge of blank NPs (Figure 1). The effect of PVA content on the physical properties of the PLGA/Eudragit RL (50:50) NPs is shown in Figure 1A. There was a decrease in particle size from 250 to 150 nm when the PVA concentration in the external aqueous phase was increased from 0% to 1% (w/v). On the other hand, the surface charge of the NPs was rapidly decreased and neutralized with PVA concentration above 0.3%. The internal/external phase ratio did not significantly influence the droplet size and zeta potential of PLGA/Eudragit RL (50:50) NPs (Figure 1B). The effect of PLGA and Eudragit RL ratio was further investigated, and the results are shown in Figure 1C and D. In the PLGA/Eudragit RL NPs with 0.1% PVA, as the proportion of the cationic polymer was increased, surface charge of NPs increased and they reached a plateau at 10% Eudragit RL, with a particle size below 200 nm (Figure 1C). However, in the case of the NPs with 1.0% PVA, the particle size was affixed to 140–180 nm with a neutral surface charge, regardless of PLGA/Eudragit RL ratio (Figure 1D). Therefore, the PLGA/Eudragit RL ratio was determined to weight ratio of 70:30, and the PVA concentration in external phase was determined to 0.1% to formulate positively surface-charged NPs. This optimized NP composition provides appropriate particle size below 200 nm, with a surface potential of over 20 mV, and was used for further in vitro and in vivo studies.

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.