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

2019 ◽  
Vol 7 (6) ◽  
pp. 460-468 ◽  
Author(s):  
Bettina Poller ◽  
Gavin F. Painter ◽  
Greg F. Walker

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.

2019 ◽  
Vol 10 ◽  
pp. 2280-2293 ◽  
Author(s):  
Nashrawan Lababidi ◽  
Valentin Sigal ◽  
Aljoscha Koenneke ◽  
Konrad Schwarzkopf ◽  
Andreas Manz ◽  
...  

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.


2017 ◽  
Vol 9 (4) ◽  
pp. 1921-1925
Author(s):  
Harshavardhan D. Joshi ◽  
V. K. Tiwari ◽  
Rupam Sharma ◽  
Subodh Gupta ◽  
W. S. Lakra ◽  
...  

The aim of present work was to develop a new Fadrozole (FDZ)-loaded Poly (D,L-lactide-co– glycolide) lactide:glycolide (50:50)(PLGA) nanoparticles for effective delivery of the masculinization drug, Fadrozole, as an alternative to commercially available masculinization agents like testosterone (dietary supplementation of 17 α- methyltestosterone) which are steroids and banned in most EU countries. The FDZ-loaded PLGA NPs were pre-pared by solvent displacement technique. The particle size of FDZ-loaded PLGA NPs was analyzed using LICOMP particle size analyser. It was found to be in the range of 60±66.7 nm to 560±66.7 nm with average size of 201.4±66.7 nm, where the Zeta potential was estimated to be about -20.82 mV, a series of experiments were carried out to induce masculinization using FDZ-loaded PLGA nanoparticles during the sex differentiation period. Tilapia, Oreochromis niloticus fry were treated with FTZ-loaded PLGA nanoparticles at dosages 5, 25, 50 and 100ppm/kg diet for 10, 15 and 30 days. The results indicated an increase in the proportion of males with dosage and duration of treatment. The male percentage was 92.35±0.86 for T7(50 ppm) at 10 days, 97.76±1.12 for T7 (100 ppm) at 15 days and 100 % for both T6 (50ppm) and T7 (100 ppm) at 30 days. This is first time done by using nanotechnology efficiently in Tilapia species which is very important Fresh water aquaculture species in present era. Which showed increase the male population with lesser dose of nano-encapsulated Fadrozole (FDZ) loaded PLGA nanoparticles drug as compared with naked control Fadrozole (FDZ) drug delivery.


1981 ◽  
Vol 103 (3) ◽  
pp. 586-590 ◽  
Author(s):  
Ruth Letan

The function performed by a direct contact heat exchanger is by definition a heat interaction between two media without an interfering wall between them. The direct contact heat exchanger analyzed herein refers to the restricted definition of systems in which temperatures of the contacted media vary without change of phase. This class involves the particulate systems of immiscible liquids, solid particles in fluids, gas bubbles in liquids, and droplets in gases. The applicability of direct contact heat exchangers has been considered for use in fouling and crystallizing systems, sea-water heating, geothermal brines, as well as in nuclear and MHD power plants. An analytic way to evaluate the performance of a direct contact heat exchanger is applied to examine the effects of operational variables upon length and diameter of a heat exchanger. The heat exchanger becomes shorter as the particle size decreases, and heat capacity ratio, flow rate ratio and approach temperature increase. The diameter of the column decreases with the particle size, and the density ratio of the contacted media. It increases with the flow rate ratio. All the evaluations made, correspond to the laminar bulk flow in the heat exchanger, and to particle Reynolds numbers in the range of 20–500.


Author(s):  
Gambhire Makarand ◽  
Vaishali Gambhire ◽  
Bhalekar Mangesh

The preparation and physico-chemical evaluation of rifam-picinloaded poly-(lactic-co-glycolic) acid (PLGA) nanoparticles as per 32 Factorial Design are presented. PLGA (X1) and PVA (Polyvinyl alcohol) solution (X2) as a stabilizing agent were used as independent variables where Particle size (PS) (Y1), Entrapment Efficiency (EE) (Y2) and % Drug Release at 12th h (REL)(Y3) were taken as dependant variables. Rifampicin nanoparticles were prepared by multiple emulsion solvent evaporation method. The results showed the method as reproducible, easy and efficient is the entrapment of drug as well as formation of spherical nanoparticles. Effect of polymer concentration was also evaluated with respect to their % drug entrapment efficiency. The in vitro release studies indicated the rifampicin-loaded PLGA nanoparticles provide sustained drug release over a period of 12h. The optimum batch was R3 which shown particle size 326 nm, 61.70 % EE and 57. 50% drug release at 12th h. Infrared spectroscopy analysis revealed that there was no known chemical interaction between drug and polymer. Hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of rifampicin nanoparticles.


2010 ◽  
Vol 7 (suppl_4) ◽  
Author(s):  
M. Enayati ◽  
Z. Ahmad ◽  
E. Stride ◽  
M. Edirisinghe

In this investigation, biodegradable polycaprolactone polymeric particles (300–4500 nm in diameter) were prepared by jetting a solution in an electric field. An extensive study has been carried out to determine how the size and size distribution of the particles generated can be controlled by systematically varying the polymer concentration in solution (and thereby its viscosity and electrical conductivity), and also the selected flow rate (2–50 µl min −1 ) and applied voltage (0–15 kV) during particle generation. Change in these parameters affects the mode of jetting, and within the stable cone-jet mode window, an increase in the applied voltage (approx. 15 kV) resulted in a reduction in particle size and this was more pronounced at high flow rates (such as; 30, 40 and 50 µl min −1 ) in the same region. The carrier particles were more polydisperse at the peripheral regions of the stable cone-jet mode, as defined in the applied voltage-flow rate parametric map. The effect of loading a drug on the particle size, size distribution and encapsulation efficiency was also studied. Release from drug-loaded particles was investigated using UV spectrophotometry over 45 days. This work demonstrates a powerful method of generating drug-loaded polymeric particles, with the ability to control size and polydispersivity, which has great potential in several categories of biotechnology requiring carrier particles, such as drug delivery and gene therapy.


Materials ◽  
2020 ◽  
Vol 13 (13) ◽  
pp. 2925 ◽  
Author(s):  
Cristina Yus ◽  
Manuel Arruebo ◽  
Silvia Irusta ◽  
Victor Sebastián

The objective of the present work was to produce gastroresistant Eudragit® RS100 nanoparticles by a reproducible synthesis approach that ensured mono-disperse nanoparticles under the size of 100 nm. Batch and micromixing nanoprecipitation approaches were selected to produce the demanded nanoparticles, identifying the critical parameters affecting the synthesis process. To shed some light on the formulation of the targeted nanoparticles, the effects of particle size and homogeneity of fluid dynamics, and physicochemical parameters such as polymer concentration, type of solvent, ratio of solvent to antisolvent, and total flow rate were studied. The physicochemical characteristics of resulting nanoparticles were studied applying dynamic light scattering (DLS) particle size analysis and electron microscopy imaging. Nanoparticles produced using a micromixer demonstrated a narrower and more homogenous distribution than the ones obtained under similar conditions in conventional batch reactors. Besides, fluid dynamics ensured that the best mixing conditions were achieved at the highest flow rate. It was concluded that nucleation and growth events must also be considered to avoid uncontrolled nanoparticle growth and evolution at the collection vial. Further, rifampicin-encapsulated nanoparticles were prepared using both approaches, demonstrating that the micromixing-assisted approach provided an excellent control of the particle size and polydispersity index. Not only the micromixing-assisted nanoprecipitation promoted a remarkable control in the nanoparticle formulation, but also it enhanced drug encapsulation efficiency and loading, as well as productivity. To the best of our knowledge, this was the very first time that drug-loaded Eudragit® RS100 nanoparticles (NPs) were produced in a continuous fashion under 100 nm (16.5 ± 4.3 nm) using microreactor technology. Furthermore, we performed a detailed analysis of the influence of various fluid dynamics and physicochemical parameters on the size and uniformity of the resulting nanoparticles. According to these findings, the proposed methodology can be a useful approach to synthesize a myriad of nanoparticles of alternative polymers.


Author(s):  
Ana Valiente ◽  
José A. Medrano ◽  
Miriam Oliva ◽  
Joaquin Ruiz ◽  
Lucía García ◽  
...  

The present work is focused on the aqueous-phase reforming of ethylene glycol at 500 K. The influence of the system pressure (27 to 36 bar) and the catalyst weight/ethylene glycol flow rate ratio has been studied using a Pt/Al2O3 research catalyst. A comparison of the latter with a Ni/Al coprecipitated catalyst showed a significant influence on hydrogen and alkane selectivities.


Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2751
Author(s):  
Mira Behnke ◽  
Antje Vollrath ◽  
Lea Klepsch ◽  
Baerbel Beringer-Siemers ◽  
Steffi Stumpf ◽  
...  

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.


2015 ◽  
Vol 7 (1) ◽  
pp. 394-399 ◽  
Author(s):  
Harshavardhan D. Joshi ◽  
Gajanan S. Ghode ◽  
Sandeep B. Gore

Males of Poecilia reticulata showed extreme diversity in color, particularly of their fins, while the females lack the bright colors and are largely whitish. Such extreme variability of color and finnage lead to demand of males in the markets. The aim of present work was to develop a new Letrozole (LTZ)-loaded PLGA nanoparticles for effective delivery of the masculinization drug, letrozole, as an alternative to commercially available masculinization agents. The LTZ-loaded PLGA NPs were prepared by solvent displacement technique. The particle size of LTZ-loaded PLGA NPs was analyzed using LICOMP particle size analyzer and was found to be in the range of 72 nm to 520 nm with average size of 221.5±63.3 nm. Zeta potential was estimated to be about 21.35 mV with loading efficiency of 43.63±4.63 %. In the present study, a series of experiments were carried out to induce masculinization using LTZ-loaded PLGA nanoparticles during the sex differentiation period. Guppy (P. reticulate) fry were treated with LTZ-loaded PLGA nanoparticles at dosages 5, 25, 50 and 100 ppm/kg diet for 10, 15 and 30 days. The gonopodium index and GSI showed increasing order in male and female respectively with dose of LTZ-loaded nanoparticles. The results indicated an increase in the proportion of males with dosage and duration of treatment. This has been done for the first time using nanotechnology efficiently which has shown an increase in the male population of Poecilia reticulata with lesser dose of nano-encapsulated Letrozole (LTZ)-loaded PLGA nanoparticles drug as compared with naked control Letrozole (LTZ) drug delivery.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ching-Min Cheng ◽  
Shang-Pang Yu ◽  
Tun-Ping Teng

This study designed an efficient one-step method for synthesizing carbon-based nanofluids (CBNFs). The method employs the vortex trap method (VTM) and an oxygen-acetylene flame, serving as a carbon source, in a manufacturing system of the VTM (MSVTM). The flow rate ratio of O2 and C2H2 was adjusted to form suitable combustion conditions for the reduced flame. Four flow rate ratios of O2 and C2H2 were used: 1.5 : 2.5 (V1), 1.0 : 2.5 (V2), 0.5 : 2.5 (V3), and 0 : 2.5 (V4). The morphology, structure, particle size, stability, and basic physicochemical characteristics of the obtained carbon-based nanomaterials (CBNMs) and CBNFs were investigated using transmission electron microscopy, field-emission scanning electron microscopy, X-ray diffraction, Raman spectrometry, ultraviolet–visible–near-infrared spectrophotometry, and a particle size-zeta potential analyzer. The static positioning method was utilized to evaluate the stability of the CBNFs with added EP dispersants. The evaluation results revealed the morphologies, compositions, and concentrations of the CBNFs obtained using various process parameters, and the relation between processing time and production rate was determined. Among the CBNMs synthesized, those obtained using the V4-0 flow rate ratio had the highest stability when no EP dispersant was added. Moreover, the maximum enhancement ratios of the viscosity and thermal conductivity were also obtained for V4-0: 4.65% and 1.29%, respectively. Different types and concentrations of dispersants should be considered in future research to enhance the stability of CBNFs for further application.


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