Comparison of bulk and microfluidics methods for the formulation of poly-lactic-co-glycolic acid (PLGA) nanoparticles modified with cell-penetrating peptides of different architectures

Streck, Sarah; Neumann, Henriette; Nielsen, Hanne Mørck; Rades, Thomas; McDowell, Arlene

doi:10.1016/j.ijpx.2019.100030

Cited by 32 publications

(45 citation statements)

References 49 publications

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“…Nanoprecipitation, as a formulation method for NPs, is impressive with its simplicity and efficiency [ 17 ] and was, therefore, applied as the first technique for the encapsulation of BRP-187 ( Figure 1 B) into PLGA particles [ 9 ]. However, the bulk procedure is often limited with respect to increasing the polymer concentration and drug loading without increasing the particle sizes and distributions as well as stability problems [ 9 , 15 ]. To overcome the lack of control and precision during particle formation by bulk preparation, the formulation of BRP-187 in PLGA particles was investigated within a herringbone staggered mixing chip ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…Improved stability, bioavailability, and efficiency of the BRP-187-loaded NPs compared to the free compound in suppressing 5-LO product formation and PGE 2 biosynthesis in intact cells were observed and underlined the promising perspective for the use of this substance/class of substances in the near future [ 9 ]. In view of upcoming in vivo studies or clinical applications, the formulation still lacks control and precision, particularly in terms of higher LC values and scale-up possibilities [ 15 , 16 , 17 ]. Thus, in order to eliminate the drawback of the conventional bulk nanoprecipitation method [ 15 ] and to increase the final drug loading capacity while the size and dispersity of the particles remain similar, the preparation of the PLGA(BRP-187) NPs was transferred from batch nanoprecipitation to a microfluidic approach in the presented study.…”

Section: Introductionmentioning

confidence: 99%

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Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

et al. 2020

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The dual inhibitor of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E2 synthase-1 (mPGES-1), named BRP-187, represents a promising drug candidate due to its improved anti-inflammatory efficacy along with potentially reduced side effects in comparison to non-steroidal anti-inflammatory drugs (NSAIDs). However, BRP-187 is an acidic lipophilic drug and reveals only poor water solubility along with a strong tendency for plasma protein binding. Therefore, encapsulation in polymeric nanoparticles is a promising approach to enable its therapeutic use. With the aim to optimize the encapsulation of BRP-187 into poly(lactic-co-glycolic acid) (PLGA) nanoparticles, a single-phase herringbone microfluidic mixer was used for the particle preparation. Various formulation parameters, such as total flow rates, flow rate ratio, the concentration of the poly(vinyl alcohol) (PVA) as a surfactant, initial polymer concentration, as well as presence of a co-solvent on the final particle size distribution and drug loading, were screened for best particle characteristics and highest drug loading capacities. While the size of the particles remained in the targeted region between 121 and 259 nm with low polydispersities (0.05 to 0.2), large differences were found in the BRP-187 loading capacities (LC = 0.5 to 7.29%) and drug crystal formation during the various formulations.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

et al. 2020

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“…Taking into account the successfulness of PLGA in DDS, the rapidly developing microfluidic technology was quickly introduced into the formulation of PLGA micor-and nanoparticles. Different chip geometries, formulation compounds and PLGA conjugates were explored, demonstrating improved control over the particle properties and resulting in various sophisticated PLGA-based nanocarrier systems [64][65][66].…”

Section: Introductionmentioning

confidence: 99%

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

et al. 2021

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Amphiphilic block co-polymer nanoparticles are interesting candidates for drug delivery as a result of their unique properties such as the size, modularity, biocompatibility and drug loading capacity. They can be rapidly formulated in a nanoprecipitation process based on self-assembly, resulting in kinetically locked nanostructures. The control over this step allows us to obtain nanoparticles with tailor-made properties without modification of the co-polymer building blocks. Furthermore, a reproducible and controlled formulation supports better predictability of a batch effectiveness in preclinical tests. Herein, we compared the formulation of PLGA-PEG nanoparticles using the typical manual bulk mixing and a microfluidic chip-assisted nanoprecipitation. The particle size tunability and controllability in a hydrodynamic flow focusing device was demonstrated to be greater than in the manual dropwise addition method. We also analyzed particle size and encapsulation of fluorescent compounds, using the common bulk analysis and advanced microscopy techniques: Transmission Electron Microscopy and Total Internal Reflection Microscopy, to reveal the heterogeneities occurred in the formulated nanoparticles. Finally, we performed in vitro evaluation of obtained NPs using MCF-7 cell line. Our results show how the microfluidic formulation improves the fine control over the resulting nanoparticles, without compromising any appealing property of PLGA nanoparticle. The combination of microfluidic formulation with advanced analysis methods, looking at the single particle level, can improve the understanding of the NP properties, heterogeneities and performance.

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“…Poly (lactic-co-glycolic acid) (PLGA)-based particles is one of the most effective biodegradable polymeric particles and the only FDA-approved IA delivery system ( 42 ). However, due to their negative surface charge ( 43 ), the PLGA-based drug delivery systems are not effective for targeting middle and deep cartilage unless extremely high drug doses are used ( 39, 44 ). Compared to the above nanoparticles, phospholipid micelles we used here for loading sPLA 2 i have several advantages.…”

Section: Discussionmentioning

confidence: 99%

Phospholipase A₂inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

Wei

Yan

Luo

et al. 2021

Preprint

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Treating osteoarthritis (OA) remains a major clinical challenge. Despite recent advances in drug discovery and development, no disease-modifying drug for knee OA has emerged with any significant clinical success, in part due to the lack of valid and responsive therapeutic targets and poor drug delivery within knee joints. In this work, we show that the amount of secretory phospholipase A2 (sPLA2) enzyme increases in articular cartilage in human and mouse OA cartilage tissues. We hypothesize that inhibition of sPLA2 activity may be an effective treatment strategy for OA. To develop a sPLA2-responsive and nanoparticle (NP)-based interventional platform for OA management, we incorporated a sPLA2 inhibitor (sPLA2i) into the phospholipid membrane of micelles. The engineered sPLA2i-loaded micellar nanoparticles (sPLA2i-NPs) were able to penetrate deep into the cartilage matrix, prolong retention in the joint space, and mitigate OA progression. These findings suggest that sPLA2i-NPs can be promising therapeutic agents for OA treatment.

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Comparison of bulk and microfluidics methods for the formulation of poly-lactic-co-glycolic acid (PLGA) nanoparticles modified with cell-penetrating peptides of different architectures

Abstract: Graphical abstract

Cited by 32 publications

References 49 publications

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Phospholipase A₂inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

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Comparison of bulk and microfluidics methods for the formulation of poly-lactic-co-glycolic acid (PLGA) nanoparticles modified with cell-penetrating peptides of different architectures

Abstract: Graphical abstract

Cited by 32 publications

References 49 publications

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics

Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Phospholipase A2inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression

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Product

Resources

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Phospholipase A₂inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression