Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration

Great challenges still remain to develop drug carriers able to penetrate biological barriers (such as the dense mucus in cystic fibrosis) and for the treatment of bacteria residing in biofilms, embedded in mucus. Drug carrier systems such as nanoparticles (NPs) require proper surface chemistry and small size to ensure their permeability through the hydrogel-like systems. We have employed a microfluidic system to fabricate poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with a muco-penetrating stabilizer (Pluronic), with a tunable hydrodynamic diameter ranging from 40 nm to 160 nm. The size dependence was evaluated by varying different parameters during preparation, namely polymer concentration, stabilizer concentration, solvent nature, the width of the focus mixing channel, flow rate ratio and total flow rate. Furthermore, the influence of the length of the focus mixing channel on the size was evaluated in order to better understand the nucleation–growth mechanism. Surprisingly, the channel length was revealed to have no effect on particle size for the chosen settings. In addition, curcumin was loaded (EE% of ≈68%) very efficiently into the nanoparticles. Finally, the permeability of muco-penetrating PLGA NPs through pulmonary human mucus was assessed; small NPs with a diameter of less than 100 nm showed fast permeation, underlining the potential of microfluidics for such pharmaceutical applications.

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Influence of Albumin in the Microfluidic Synthesis of PEG-PLGA Nanoparticles

Pharmaceutical Nanotechnology ◽

10.2174/2211738507666191023091938 ◽

2019 ◽

Vol 7 (6) ◽

pp. 460-468 ◽

Cited By ~ 1

Author(s):

Bettina Poller ◽

Gavin F. Painter ◽

Greg F. Walker

Keyword(s):

Particle Size ◽

Aqueous Phase ◽

Flow Rate ◽

Coefficient Of Variation ◽

Polymer Concentration ◽

Plga Nanoparticles ◽

Organic Polymer ◽

Flow Rate Ratio ◽

Aqueous Solvent ◽

Average Size

Background: A key challenge in the manufacturing of polymeric colloids is producing nanoparticles with good batch-to-batch consistency. Objective: Develop a robust microfluidics method for the preparation of PEG-PLGA nanoparticles using dimethyl sulfoxide (DMSO) as the organic phase solvent for the encapsulation of DMSO soluble agents. Method: Microfluidic process parameters, total flow rate (10 mL/min), flow rate ratio (1:1) of the aqueous phase and the organic polymer solution, and polymer concentration (5 mg/ml). Polyvinyl alcohol (PVA) or human serum albumin (HSA) was included in the aqueous phase. Dynamic light scattering and transmission electron microscopy were used to investigate the size and morphology of particles. Results: PLGA nanoparticles made using DMSO with the aqueous solvent containing PVA (2%) had an average size of 60 nm while PLGA-PEG nanoparticles made with and without PVA (2%) had an average size of 70 and 100 nm, respectively. PLGA-PEG nanoparticles generated with or without PVA had a high batch-to-batch coefficient of variation for the particle size of 20% while for PLGA nanoparticles with PVA it was 4%. HSA added to the aqueous phase reduced the size and the zeta potential of PEG-PLGA nanoparticles as well the batch-to-batch coefficient of variation for particle size to < 5%. Nanoparticles were stable in solution and after lyophilized in the presence of sucrose. Conclusion: Albumin was involved in the self-assembly of PEG-PLGA nanoparticles altering the physicochemical properties of nanoparticles. Adding protein to the aqueous phase in the microfluidic fabrication process may be a valuable tool for tuning the properties of nanoparticles and improving batch-to-batch consistency.

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Characterization and Aerosolization Performance of HydroxyPropyl-Beta-Cyclodextrin Particles Produced Using Supercritical Assisted Atomization

Polymers ◽

10.3390/polym13142260 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2260

Author(s):

Hsien-Tsung Wu ◽

Yao-Hsiang Chuang ◽

Han-Cyuan Lin ◽

Liang-Jung Chien

Keyword(s):

Carbon Dioxide ◽

Flow Rate ◽

Rate Ratio ◽

Aqueous Ethanol ◽

Drug Carriers ◽

Ethanol Solution ◽

Spherical Particles ◽

Flow Rate Ratio ◽

Beta Cyclodextrin ◽

Hydroxypropyl Beta Cyclodextrin

In this study, hydroxypropyl-beta-cyclodextrin (HP-β-CD) particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium or co-solute and aqueous ethanol solution as the solvent. The effects of several key factors on the morphology and size of the HP-β-CD particles were investigated. These factors included the solvent effect, temperatures of the precipitator and saturator, concentration of the HP-β-CD solution, and flow rate ratio of carbon dioxide to the HP-β-CD solution. The conducive conditions for producing fine spherical particles were 54.2% (w/w) aqueous ethanol as the solvent; precipitator and saturator temperatures of 373.2 K and 353.2 K, respectively; a flow rate ratio of carbon dioxide to HP-β-CD solution of 1.8; and low concentrations of HP-β-CD solution. The addition of leucine (LEU) enhanced the aerosol performance of the HP-β-CD particles, and the fine particle fraction (FPF) of the HP-β-CD particles with the addition of 13.0 mass% LEU was 1.8 times higher than that of the HP-β-CD particles without LEU. This study shows that LEU can act as a dispersion enhancer and that HP-β-CD particles produced using SAA can be used as pulmonary drug carriers.

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Swelling characterization of photo-cross-linked gelatin methacrylate spherical microgels for bioencapsulation

e-Polymers ◽

10.1515/epoly-2014-0025 ◽

2014 ◽

Vol 14 (3) ◽

pp. 161-168 ◽

Cited By ~ 3

Author(s):

Jinmu Jung ◽

Jonghyun Oh

Keyword(s):

Flow Rate ◽

Rate Ratio ◽

Axial Flow ◽

Microfluidic System ◽

Low Flow ◽

Flow Rate Ratio ◽

Swelling Characteristics ◽

Irradiation Apparatus ◽

Proportional Relationship

AbstractThe swelling behavior of biocompatible and biodegradable polymers is important for the delivery and release of cells and drugs in biomedical applications. This study reported the swelling characteristics of photo-cross-linked gelatin methacrylate (GelMa) spherical microgels. Spherical microgels were generated in a microfluidic system consisting of a co-axial flow-focusing device for microdroplet generation and an ultraviolet (UV) irradiation apparatus for polymerization. At a low flow rate ratio (<0.14), the 9 wt.% GelMa spherical microgels were smaller than the 6 wt.% ones. In contrast, at a high flow rate ratio (>0.14), the results were reversed. Overall, a proportional relationship was observed between the flow rate ratio and the droplet size. The increased GelMa concentration improved the mechanical properties and increased the swelling ratios. The possibility of bioencapsulation was demonstrated, with good viability of 3T3 cells encapsulated in the spherical microgels.

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

Polymers ◽

10.3390/polym12112751 ◽

2020 ◽

Vol 12 (11) ◽

pp. 2751

Author(s):

Mira Behnke ◽

Antje Vollrath ◽

Lea Klepsch ◽

Baerbel Beringer-Siemers ◽

Steffi Stumpf ◽

...

Keyword(s):

Drug Loading ◽

Polymer Concentration ◽

Plga Nanoparticles ◽

Flow Rate Ratio ◽

Poly Vinyl Alcohol ◽

Drug Candidate ◽

Crystal Formation ◽

Dual Inhibitor ◽

Final Particle ◽

Anti Inflammatory

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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Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170911170104 ◽

2018 ◽

Vol 18 (2) ◽

pp. 302-311

Author(s):

Shulin Dai ◽

Yucheng Feng ◽

Shuyi Li ◽

Yuxiao Chen ◽

Meiqing Liu ◽

...

Keyword(s):

Glutamic Acid ◽

Drug Carrier ◽

Drug Loading ◽

Drug Carriers ◽

Cancer Drug ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Anti Cancer ◽

Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

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Absorption of oxygen into solutions of polymers

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19862127 ◽

1986 ◽

Vol 51 (10) ◽

pp. 2127-2134 ◽

Cited By ~ 1

Author(s):

František Potůček ◽

Jiří Stejskal

Keyword(s):

Mass Transfer ◽

Aqueous Solutions ◽

Transfer Coefficient ◽

Mass Transfer Coefficient ◽

Flow Rate ◽

Liquid Flow ◽

Flow Curve ◽

Liquid Flow Rate ◽

Polymer Concentration ◽

Newtonian Liquids

Absorption of oxygen into water and aqueous solutions of poly(acrylamides) was studied in an absorber with a wetted sphere. The effects of changes in the liquid flow rate and the polymer concentration on the liquid side mass transfer coefficient were examined. The results are expressed by correlations between dimensionless criteria modified for non-Newtonian liquids whose flow curve can be described by the Ostwald-de Waele model.

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Semi-Crystalline Copolymer Hydrogels as Smart Drug Carriers: In Vitro Thermo-Responsive Naproxen Release Study

Pharmaceutics ◽

10.3390/pharmaceutics13020158 ◽

2021 ◽

Vol 13 (2) ◽

pp. 158

Author(s):

Snežana Ilić-Stojanović ◽

Ljubiša Nikolić ◽

Vesna Nikolić ◽

Slobodan Petrović ◽

Violeta Oro ◽

...

Keyword(s):

Drug Carrier ◽

Drug Carriers ◽

Xrd Analysis ◽

Hplc Method ◽

Potential Candidate ◽

Swelling Kinetic ◽

Model Drug ◽

Xrd Techniques ◽

Responsive Hydrogels

In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of application as a thermo-responsive carrier for prolonged naproxen release in order to evaluate as a potential candidate for drug carrier in future pharmaceutical applications.

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Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation

Nanomaterials ◽

10.3390/nano11010152 ◽

2021 ◽

Vol 11 (1) ◽

pp. 152

Author(s):

Iulia Pinzaru ◽

Cristian Sarau ◽

Dorina Coricovac ◽

Iasmina Marcovici ◽

Crinela Utescu ◽

...

Keyword(s):

Antitumor Activity ◽

Betulinic Acid ◽

Water Solubility ◽

Physicochemical Characterization ◽

A549 Cells ◽

Drug Carriers ◽

Biological Evaluation ◽

Correlation Spectroscopy ◽

Hydrodynamic Diameter

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models—hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

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Continuous Flow Controlled Synthesis of Gold Nanoparticles Using Pulsed Mixing Microfluidic System

Advances in Materials Science and Engineering ◽

10.1155/2015/160819 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Guojun Liu ◽

Xuhao Yang ◽

Yan Li ◽

Zhigang Yang ◽

Wen Hong ◽

...

Keyword(s):

Gold Nanoparticles ◽

Flow Rate ◽

Research Work ◽

Microfluidic System ◽

Noble Metal Nanoparticles ◽

Controlled Synthesis ◽

Entrance Angle ◽

Section Size ◽

Pulsed Mixing ◽

Entrance Flow

To prepare the gold nanoparticles (AuNPs) with uniform sizes, fine morphology, and good monodispersity, a pulsed mixing microfluidic system based on PZT actuation was presented. The system includes PZT micropump and Y type micromixer. By adjusting voltage (entrance flow rate), pulsed frequency, phase, and other parameters, a variety of mixing modes can be achieved, so as to realize the controllable synthesis of nanoparticles in a certain range. By numerical simulation and analysis, the channel section size, entrance angle, and pulse frequency were optimized. Based on the optimized structure and working parameters, the test prototype has been manufactured in lab, and the related synthesis tests of AuNPs were carried out. The test results indicate that AuNPs with uniform morphology and good monodispersity can be synthesized using the system with the section size (0.4 mm × 0.4 mm), the entrance channel angle (60°) under condition of the pulsed frequency (300 Hz), and the entrance flow rate (4 mL/min). The average diameter and its standard deviation of AuNPs synthesized were 21.6 nm, 4.83 nm, respectively. The research work above can be applied to the fields such as the controlled synthesis of noble metal nanoparticles, biomedicine, and microchemical system.

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