Goran Vladisavljević - Academia.edu (original) (raw)

Papers by Goran Vladisavljević

Chemical Engineering Science, Feb 1, 2019

A novel microfluidic mixing strategy was developed and used to prepare polyvinylpyrrolidone (PVP)... more A novel microfluidic mixing strategy was developed and used to prepare polyvinylpyrrolidone (PVP) capped gold nanoparticles (AuNPs). In this process, 1 mM tetrachloroauric acid (HAuCl4) stream containing 1% (w/v) PVP was injected through the inner capillary tube and mixed with 20 mM L-ascorbic acid solution delivered co-currently through the outer coaxial capillary. The reaction mixture was hydrodynamically flow focused by the environmentally friendly oil Miglyol 840 delivered from the opposite side of the outer capillary, which resulted in the generation of reaction droplets in a tapered collection tube. The reactants were rapidly mixed within droplets by internal circulating flows induced by hydrodynamic interactions of fluids inside the droplets with the carrier oil. The size of the prepared AuNPs was measured by both dynamic light scattering and transmission electron microscopy and was found to decrease with decreasing the droplet size and increasing the difference in velocity between the two reactant streams, which improved mixing efficiency within droplets. The smallest nanoparticles were obtained when the outlet section of the injection tube was positioned at the entry section of the collection tube due to the highest shear at the liquid interface. The carrier oil formed a hydrophobic barrier between the droplets and the reactor walls preventing deposition of the synthesised particles. As a result, the size of the AuNPs was smaller than in the co-flow mixer operated with two continuous reactant streams.

RSC Advances, 2013

Liposomes with a mean size of 59−308 nm suitable for pulmonary drug delivery were prepared by the... more Liposomes with a mean size of 59−308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of 5−40 μm and a pore spacing of 80 or 200 μm. An ethanolic phase containing 20−50 mg/ml phospholipid (1-palmitoyl-2-oleoylsn-glycero-3-phosphocholine (POPC) or Lipoid® E80), 5−12.5 mg/ml stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg/ml vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142−355 l/m 2 /h and a shear stress on the membrane surface of 0.80−16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of prepared liposomes increased with increasing the pore size of the membrane and decreased with increasing the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. A reproducibility of the developed fabrication method was high.

ACS Applied Bio Materials

Monodispersed sirolimus (SRL)-loaded poly(lacticco-glycolic acid) microspheres with a diameter of... more Monodispersed sirolimus (SRL)-loaded poly(lacticco-glycolic acid) microspheres with a diameter of 1.8, 3.8, and 8.5 μm were produced by high-throughput microfluidic step emulsification�solvent evaporation using single crystal silicon chips consisted of 540−1710 terraced microchannels with a depth of 2, 4, or 5 μm arranged in 10 parallel arrays. Uniform sized droplets were generated over 25 h across all channels. Nearly 15% of the total drug was released by the initial burst release during an accelerated drug release testing performed at 37°C using a hydrotropic solution containing 5.8 M N,N-diethylnicotinamide. After 24 h, 71% of the drug was still entrapped in the particles. The internal morphology of microspheres was investigated by fluorescence microscopy using Nile red as a selective fluorescent stain with higher binding affinity toward SRL. By increasing the drug loading from 33 to 50 wt %, the particle morphology evolved from homogeneous microspheres, in which the drug and polymer were perfectly mixed, to patchy particles, with amorphous drug patches embedded within a polymer matrix to anisotropic patchy Janus particles. Janus particles with fully segregated drug and polymer regions were achieved by pre-saturating the aqueous phase with the organic solvent, which decreased the rate of solvent evaporation and allowed enough time for complete phase separation. This approach to manufacturing drug-loaded monodisperse microparticles can enable the development of more effective implantable drug-delivery devices and improved methods for subcutaneous drug administration, which can lead to better therapeutic treatments.

Journal of Colloid and Interface Science, 2022

Double emulsions with many monodispersed internal droplets are required for the fabrication of mu... more Double emulsions with many monodispersed internal droplets are required for the fabrication of multicompartment microcapsules and tissue-like synthetic materials. These double emulsions can also help to optically resolve different coalescence mechanisms contributing to double emulsion destabilization. Up to date microfluidic double emulsions are limited to either core-shell droplets or droplets with eight or less inner droplets. By applying a two-step jet break-up within one setup, double emulsion droplets filled with up to several hundred monodispersed inner droplets can be achieved. Experiments Modular interconnected CNC-milled Lego-inspired blocks were used to create two separated droplet break-up points within coaxial glass capillaries. Inner droplets were formed by countercurrent flow 2 focusing within a small inner capillary, while outer droplets were formed by co-flow in an outer capillary. The size of inner and outer droplets was independently controlled since the two droplet break-up processes were decoupled. Findings With the developed setup W/O/W and O/W/O double emulsions were produced with different surfactants, oils, and viscosity modifiers to encapsulate 25 to 400 inner droplets in each outer drop with a volume percentage of inner phase between 7% and 50%. From these emulsions monodispersed multicompartment microcapsules were obtained. The report offers insights on the relationship between the coalescence of internal droplets and their release.

Molecules, 2021

This article provides a systematic review of the crosslinking strategies used to produce microgel... more This article provides a systematic review of the crosslinking strategies used to produce microgel particles in microfluidic chips. Various ionic crosslinking methods for the gelation of charged polymers are discussed, including external gelation via crosslinkers dissolved or dispersed in the oil phase; internal gelation methods using crosslinkers added to the dispersed phase in their non-active forms, such as chelating agents, photo-acid generators, sparingly soluble or slowly hydrolyzing compounds, and methods involving competitive ligand exchange; rapid mixing of polymer and crosslinking streams; and merging polymer and crosslinker droplets. Covalent crosslinking methods using enzymatic oxidation of modified biopolymers, photo-polymerization of crosslinkable monomers or polymers, and thiol-ene “click” reactions are also discussed, as well as methods based on the sol−gel transitions of stimuli responsive polymers triggered by pH or temperature change. In addition to homogeneous mic...

Monodispersed magnetic Janus particles composed of a porous polystyrene portion and a nonporous p... more Monodispersed magnetic Janus particles composed of a porous polystyrene portion and a nonporous poly(vinyl acetate) portion with embedded oleic acid-coated magnetic nanoparticles were generated using microfluidic emulsification followed by two distinct phase separation events triggered by solvent evaporation. The template droplets were composed of 2 wt% polystyrene, 2 wt% poly(vinyl acetate) and 0.5-2 wt% n-heptane-based magnetic fluid dissolved in dichloromethane (DCM). The porosity of polystyrene compartments was the result of phase separation between a non-volatile non-solvent (n-heptane) and a volatile solvent (DCM) within polystyrene-rich phase. The focused ion beam cross-sectioning and SEM imaging revealed high surface porosity of polystyrene compartments with negligible porosity of poly(vinyl acetate) parts, which can be exploited to increase the wettability contrast between the two polymers and enhance bubble generation in bubble-driven micromotors. The porosity of the polystyrene portion was controlled by varying the fraction of n-heptane in the dispersed phase. The particle composition was confirmed by scanning electron microscopy-energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The fabricated particles were successfully magnetised when subjected to an external magnetic field, which led to their aggregation into regular 2D assemblies. The particle clusters composed of 2-4 individual particles could be rotated with a rotating magnetic field. Microfluidic generation of highly porous Janus particles with compositional, topological, and magnetic asymmetry provides a cost-effective, easy-to-implement yet highly robust and versatile strategy for the manufacturing of multifunctional smart particles.

Chemical Engineering Science, 2019

Journal of the Serbian Chemical Society, 2000

The preparation of fine and monodispersed water-in-oil (W/O) emulsions by utilizing hydrophobic h... more The preparation of fine and monodispersed water-in-oil (W/O) emulsions by utilizing hydrophobic hollow polypropylene fibers with 0.4 mm pores was investigated in this work. The experiments were carried out using demineralized water as the disperse phase, mineral oil Velocite No. 3 as the continuous phase, and polyglycerol polyricinoleate (PGPR 90) in the concentration range of 2.5 - 10 wt % as the oil-soluble emulsifier. The size of the water droplets in the prepared emulsions and the droplet size distribution strongly depend on the content of the disperse phase, the transmembrane pressure difference, and the emulsifier concentration. Stable emulsions with a very narrow droplet size distribution and a mean droplet diameter lower than 0.27 ?m were produced using 10 wt % PGPR 90 at a pressure difference below 30 kPa.

PloS one, 2017

The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global healt... more The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate) using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in t...

Advances in colloid and interface science, Jan 14, 2017

Against a backdrop of global antibiotic resistance and increasing awareness of the importance of ... more Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don't present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, ...

Langmuir : the ACS journal of surfaces and colloids, Jan 30, 2016

Rapamycin loaded polycaprolactone nanoparticles (RAPA-PCL NPs) with a low polydispersity index of... more Rapamycin loaded polycaprolactone nanoparticles (RAPA-PCL NPs) with a low polydispersity index of 0.006-0.073 were produced by anti-solvent precipitation using a ringed stainless steel membrane with 10-μm diameter laser-drilled pores. The organic phase composed of 6 g L(-1) of PCL and 0.6-3.0 g L(-1) of RAPA in acetone was injected through the membrane at 140 L m(-2) h(-1) into 0.2 wt% aqueous polyvinyl alcohol solution stirred at 1300 rpm, resulting in a Z-average mean of 189-218 nm, a drug encapsulation efficiency of 98.8-98.9 % and a drug loading in the NPs of 9-33 %. The encapsulation of RAPA was confirmed by UV-Vis spectroscopy, XRD, DSC, and ATR-FTIR. The disappearance of sharp characteristic peaks of crystalline RAPA in the XRD pattern of RAPA-PCL NPs revealed that the drug was molecularly dispersed in the polymer matrix or present in individual amorphous domains. The rate of drug release in pure water was negligible due to low aqueous solubility of RAPA. RAPA-PCL NPs release...

Encyclopedia of Membranes, 2016

Quite often during the operation of a system for the treatment of gases, it is necessary to expan... more Quite often during the operation of a system for the treatment of gases, it is necessary to expand it for treating greater streams. In some cases, future expansion is contemplated even during the initial phase of a project. In other cases, it could be a necessity not foreseen during system design phase (Miller and Stöcker 1989; Brunetti et al. 2010). Membrane system expansion is very easy, since this only requires the addition of identical modules. This is the advantage offered by the modularity of membrane units and the reduced equipment and control systems required for operating it. In comparison, considering the other reference technologies for gas separation, PSA and absorption systems can also be expanded, but it requires additional design considerations and adds cost in the initial phase of the project. The cryogenic units cannot be expanded if it is not foreseen during the design phase. Generally they can be over-dimensioned, and a capacity increase is often obtained without modification to the cold box itself through addition of a tail gas compressor. References Brunetti A, Bernardo P, Drioli E, Barbieri G (2010) Membrane engineering progresses and potentialities in gas separations. In: Yampolskii Y, Freeman B (eds) Membrane gas separation. Wiley, New York, pp 281-312 Miller GQ, Stöcker J (1989) Selection of a hydrogen separation process NPRA annual meeting, 19

Chemical Engineering Journal, 2016

Highlights  Size-tuneable NPs were formed by nanoprecipitation using microenginered membrane  A... more Highlights  Size-tuneable NPs were formed by nanoprecipitation using microenginered membrane  A good micromixing favoured nucleation and led to a reduction in the particle size  The minimum particle size was 159 nm with a polydispersity index (PDI) of 0.107  Membrane with ringed operating area provided better performance than full membrane  Laser-drilled pores led to smaller NPs than conical nickel electroformed pores *Highlights (for review)

Physical Sciences Reviews, 2016

Encyclopedia of Membranes, 2014

Contemporary Food Engineering, 2015

This chapter deals with the production, properties, and macrofluidic applications of Shirasu Poro... more This chapter deals with the production, properties, and macrofluidic applications of Shirasu Porous Glass (SPG) membrane. The first section provides an overview of the membrane microfluidic processes used for production and modification of liquid-liquid and gas-liquid micro-and nano-dispersions, such as direct and premix membrane emulsification with and without phase inversion, membrane demulsification, membrane micromixing / direct precipitation and micro-and nano-bubbling. In the last section of this chapter, SPG membranes are compared with conventional homogenisers and microfluidic drop generators in terms of production rate, droplet size uniformity, and applied shear stresses. The second section deals with the fabrication of SPG membrane by spinodal decomposition in Na 2 O-CaO-Al 2 O 3-B 2 O 3-SiO 2 type glass and morphological, mechanical, and hydrodynamic properties of SPG membrane. This chapter also covers modification of surface charge, contact angle and porosity of SPG membrane using different physical and chemical methods, such as deposition of silica nanoparticles onto membrane surface, coating with silicon resin, filling the pores with solvent-responsive polymer chains and chemical modification with silane coupling agents. The fourth section is focused on the effects of physical properties of the dispersed and continuous phase, operating parameters and membrane properties on the droplet size in direct and premix SPG membrane emulsification. In addition, the most common classes of micro-and nano-particles fabricated using SPG membrane were reviewed and their fabrication routes were discussed. It was concluded that a broad variety of different chemical and physicochemical processes can be combined with SPG membrane emulsification to convert droplets into uniform particle. The last section briefly discusses the generation of micro-and nano-bubbles using SPG membrane.

Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014

Food-grade water-in-oil-in-water (W/O/W) multiple emulsions with a volume median diameter of oute... more Food-grade water-in-oil-in-water (W/O/W) multiple emulsions with a volume median diameter of outer droplets of 50−210 μm were produced by injecting a water-in-oil (W/O) emulsion at the flux of 30 L m −2 h −1 through a 10-μm pore electroplated nickel membrane oscillating at 10−90 Hz frequency and 0.1−5 mm amplitude in 2 wt% aqueous Tween ® 20 (polyoxyethylene sorbitan monolaurate) solution. The oil phase in the primary W/O emulsion was 5 wt% PGPR (polyglycerol polyricinoleate) dissolved in sunflower oil and the content of water phase in the W/O emulsion was 30 vol%. The size of outer droplets was precisely controlled by the amplitude and frequency of membrane oscillation. Only 3−5 % of the inner droplets with a mean diameter of 0.54 µm were released into the outer aqueous phase during membrane emulsification. A sustained release of 200 ppm copper (II) loaded in the inner aqueous phase was investigated over 7 days. 95% of Cu(II) initially present in the inner water phase was released in the first 2 days from 56-µm diameter multiple emulsion droplets and less than 15 % of Cu(II) was released over the same interval from 122 µm droplets. The release rate of Cu(II) decreased with increasing the size of outer droplets and followed nonzero-order kinetics with a release exponent of 0.3−0.5. The prepared multiple emulsions can 2 be used for controlled release of hydrophilic actives in the pharmaceutical, food, and cosmetic industry.