Posters:
New formulation: Encapsulation of insulin in nanoparticles for oral administration
BENAZIZ Ouarda
Département de pharmacie. Universoté SAAD DAHLAB de Blida
The objective of this study was to develop alginate/chitosan nanoparticles to deliver model protein drug insulin to protect it from gastric passage,using ionotropic pre-gelation method of an alginate core with calcium chloride followed by chitosan complexation.
The characterization of different properties of prepared nanoparticles, such as particle size, zeta potential value, morphology, stability, structure, and drug loading was studied. The release of insulin from nanoparticles at acidic and alkaline environment was also evaluated. The results indicate that the insulin loaded mucoadhesive nanoparticles was a key factor in the improvement of its oral absorption.
Proteins are important therapeutic molecules because they have multiple biological functions; however, the development of a drug-based protein is the origin of many difficulties due to their specific properties and their sensitivity to environmental conditions.
Proteins have low oral and transdermal bioavailability, they are usually administered parenterally. However, most proteins have a very short half-life, requiring frequent injections, which is not well tolerated by patients and may limit the extent of therapies based on protein.
Microencapsulation of peptides and proteins and the preparation of sustained-release forms have been widely studied in order to improve the therapeutic efficacy of these bioactive molecules. However, the difficulties mentioned above concerning the properties of the protein, reduce the choice of an encapsulation process and imposing a strict control of operating conditions to ensure the continued integrity of the protein during all stages of production.
To this end, we propose to use an encapsulation technique based on ionic gelation between two oppositely charged polymers at room temperature polymers at room temperature.
The ionotropic gelation method is very simple and mild. In addition, reversible physical crosslinking by electrostatic interaction instead of chemical crosslinking avoids the possible toxicity of reagents and other undesirable effects.
The use of polysaccharides and especially natural biopolymers has attracted particular interest due to their desirable biocompatible, biodegradable, hydrophilic and protective properties. In this study, two polysaccharides, alginate and chitosan were used as polyionic polymers to associate with the model protein drug insulin. The use of chitosan in complex with alginate is a promising strategy if we consider the biocompatibility of two polyelectrolytes.
Engineering single and double droplets for flow cytometry
Shaohua MA 1, Joseph SHERWOOD2, Wilhelm T. S. HUCK 3, Stavroula BALABANI 4,*
1 Chemistry Research Laboratory, University of Oxford, UK
2 Department of Bioengineering, Imperial College London, UK
3 Institute for Molecules and Materials, Radboud University Nijmegen, The Netherlands
4 Department of Mechanical Engineering, University College London, UK
*
Microfluidic droplets have been studied extensively due to their wide applications. Knowledge of the flow field inside the droplets is of paramount importance in order to tailor microdroplets to a specific application: for example, while mixing is desirable for reaction/synthesis applications, a low shear environment is preferred for cell encapsulation. Using micro-particle image velocimetry (µPIV) we have characterized the internal flows and shear environment in w/o and w/o/w droplets generated using different droplet-carrier fluid combinations at intermediate capillary numbers (Ca) ranging from 10-3 to 0.1. The velocity data was used to estimate the distribution of hydrodynamic stresses inside the droplets in order to assess cell viability and hence suitability of the double droplet environment for flow cytometry applications, such as fluorescence activated cell sorting (FACS). We also studied the deformation of the droplets under hydrodynamic focusing conditions mimicking the sheath flows in FACS for different viscosities and surfactants in order to provide useful design guidelines. The study demonstrates that controlling and characterizing droplet flow topology provides a powerful tool towards optimizing droplet microfluidic systems. Droplet systems with higher inner-to-outer viscosity ratio and a less viscous droplet fluid should be adopted when low internal circulation is desired, e.g. in cell screening applications; however, lower viscosity ratio systems with a more viscous droplet phase are preferred when aiming for efficient mixing.
Encapsulation of Water-Soluble Compounds by Complex Coacervation and Membrane Emulsification
Alix Barton, Roslyn Holmes, Marijana Dragosavac
Loughborough University
Limited research has been conducted in encapsulating water-soluble compounds using double emulsions along with complex coacervation[1]. This research is investigating a novel way of encapsulating water-soluble compounds, along with finding FDA approved chemicals that work better in the encapsulation process due to the ethical and health issues surrounding the current chemicals used. Complex coacervation is performed predominantly by batch methods (stirring or homogenization). These methods produce droplets with large size distributions. Experiments for this project have been done using a different method, membrane emulsification using a Dispersion Cell (DC)[2,3]. This technique has the ability to produce more uniform droplets as well as having enhanced control over droplet size. A continuous phase mixture of gelatin and gum arabic and a dispersed phase of a W/O emulsion (homogenized at 1200 rpm for 4 minutes) was used. Using 10 µm stainless steel membrane, droplets in the range between 40 - 300µm were produced (Fig1a) supporting shells (Fig1b), by varying stirrer rotation speed and dispersed injection rate. Future work will focus on the control of the shell thickness and ascorbic acid[3,4] will be entrapped within the internal water phase. Scale up of the process will be performed using the azimuthally oscillating membrane emulsification system[4].
[1] Burgess, Diane J. "Complex Coacervation: Microcapsule Formation." In Macromolecular Complexes in Chemistry and Biology, by P Dubin, J Bock, R Davis, D N Schulz and C Thies, 285-300. Springer Berlin Heidelberg, Springer Berlin Heidelberg.
[2] Dragosavac, Marijana, Richard Holdich, Goran Vladisavljevic ́, and Milan Sovilj. "Stirred cell membrane emulsification for multiple emulsions containing unrefined pumpkin seed oil with uniform droplet size." Journal of Membrane Science, 2012: 122–129.
[3] Comunian , Talita, Marcelo Thomazini , Ana Julia Gouvêa Alves , Fernando Eustáquio de Matos Junior , Júlio C. de Carvalho Balieiro , and Carmen S. Favaro-Trindade . "Microencapsulation of ascorbic acid by complex coacervation: Protection and controlled release." Food Research International, 2013: 373–379 .
[4] Silva, Pedro S., Marijana M. Dragosavac, Goran T. Vladisavljević, Hemaka CH Bandulasena, Richard G. Holdich, Mike Stillwell, and Bruce Williams. "Azimuthally oscillating membrane emulsification for controlled droplet production." AIChE Journal 61, 2015, 3607-3615.
Comparison of mechanical properties of microcapsules of different architectures and production scales via micromanipulation
Andrew Gray
University of Birmingham, Procter and Gamble
Relating microcapsule performance to structure is an extremely important consideration to take when developing microcapsules, and a deeper understanding of the interconnectivity of the two areas leads to a more refined approach in creating formulations for consumer applications.
Micromanipulation is a novel technique used to study mechanical properties of microcapsules through compression of individual microcapsules against a plate under a normal force load. The response of the microcapsules to the force application is recorded against displacement, giving information on the stress-strain relationship of the shell material, deformation at rupture and rupture force.
Mechanical properties of melamine formaldehyde microcapsules, formulated through different scales of production, and polyacrylate microcapsules containing different core material were studied using the technique. This provided insight into how changing the production scale and core contents can vary mechanical properties and also afforded comparison of properties of different commercially relevant shell structures.
Controlled adsorption of metallic nanoparticles on polymeric microcapsules with a view to growing secondary continuous metal films
J.Hitchcock1*, O. J. Cayre1, and S. Biggs1
1 Institute of Particle Science, University of Leeds, Leeds, UK
*
Small, volatile actives cannot be micro-encapsulated efficiently over the lifetime of a product using current encapsulation techniques. This is due to the inherent porosity of the polymeric membranes which are used as the capsule shell material. We have developed a method for preventing undesired loss of encapsulated actives which prevents loss of the core into ethanol over 90 days +. Oil core microcapsules are produced using oil-in-water emulsification followed by co-solvent extraction to precipitate a polymeric shell around the oil core. Metallic catalytic nanoparticles are then physically adsorbed onto the microcapsules and used to catalyse the growth of a continuous secondary metallic film via electroless deposition.
It is important to have good control over the primary nanoparticle adsorption density which requires a good control over and understanding of the original nanoparticle (NP) synthesis. In this work we use Quartz crystal microbalance (QCM) and transmission electron microscopy (TEM) to demonstrate the ability to control NP adsorption densities by varying several parameters such as concentration of polymeric stabiliser used in the original NP dispersion synthesis and NP dispersion concentration. We show that NP films form in seconds and demonstrate good adsorption energies. We also discuss/explain the semi regular hexagonal packing of the NP cores we observe under TEM.
Keywords: nanoparticles, metal shell, catalysts, adsorption, microencapsulation, quartz crystal microbalance.
Enhancing deposition of microcapsules on hair
Javier Marques de Marino1, Pierre Verstraete2, Zhibing Zhang1
- School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT
- Procter & Gamble Brussels innovation Centre (BIC) Temselaan 100, 1853 Strombeek Bever
In the hair care industry, there is interest to improve the performance of its products by delivering “active molecules” onto the hair. Thus, the interaction between microcapsule and hair fibre has to be analysed. The measurements of the adhesive force were carried with an atomic force microscope (AFM) in DI water conditions; different hair types, non-treated and chemically damaged (bleaching process), were used. It has been found the bleaching process reduce a 66% the pulling off force; the removal of 18-MEA (outer layer of the cuticle) during the bleaching process is believed to be the responsible for the decrease.
Polydimethylsiloxane (PDMS) and Amino functional silicone (ADMS) were used to enhance the adhesion of the microcapsules by coating the hair with these chemicals. To determine the new properties of the hair a modified Wilhelmy balance and a scanning electron microscope (SEM) were used. When the hair is coated with PDMS an increase in the adhesive force over 351% (Chemically damaged) and 92.5% (Non-treated) was found, whereas for ADMS it was over 265% (Chemically damaged) and 29% (Non-treated). The different factors that cause this increment are discussed.
Polymeric microparticles produced by Membrane Emulsification for targeted drug and cells delivery
S.Morelli*, R.G.Holdich*, M.M.Dragosavac*
*Chemical Engineering department, Loughborough University, Leicestershire, UK
Targeted drug and cell delivery in specific area of human body is a method to overcome some of the disadvantages typical for the conventional drug administration methods1. Biocompatible polymers can be used for production of advanced formulations able to respond to environmental stimuli (e.g. pH-change). Polymeric formulations represent a promising approach for cells immobilization and delivery2,3. In this work the Dispersion Cell Membrane Emulsification4 with metallic membranes (Micropore Technology Ltd., UK) was used for production of microparticles for targeted drug and cell encapsulation and subsequently delivery. Polymeric droplets produced by the Dispersion Cell were solidified into microparticles. Modifying the operating parameters of the process highly uniform particles in the range between 30 and 160 µm were produced. One set of experiments consisted of loading the microparticles with copper and monitoring the release profile with time at pH 3 and 7 to mimic the stomach and intestine conditions. With the right blend of polymers (PVA & Chitosan) particles would release more in acidic environment; making them suitable for stomach release. In other set of experiments living yeast cells (average size 7 µm) were encapsulated within a polymer matrix and the cells availability was assayed measuring the yeast glucose consumption with time.
Reference:
1. Hillery AM, Lloyd AW, Swarbrick J. Drug Delivery and Targeting: For Pharmacists and Pharmaceutical Scientists. Taylor and. CRC Press; 2002.
2. Raymond MC, Neufeld RJ, Poncelet D. Encapsulation of brewers yeast in chitosan coated carrageenan microspheres by emulsification/thermal gelation. Artif. cells, blood substitutes, Biotechnol. 2004;32(2):275-291.
3. Park JK, Chang HN. Microencapsulation of microbial cells. Biotechnol. Adv. 2000;18(4):303-319.
4. Stillwell MT, Holdich RG, Kosvintsev SR, Gasparini G, Cumming IW. Stirred Cell Membrane Emulsification and Factors Influencing Dispersion Drop Size and Uniformity. Ind. Eng. Chem. Res. 2007;46(3):965-972.
New formulation: Encapsulation of insulin in nanoparticles for oral administration
BENAZIZ Ouarda
Département de pharmacie. Universoté SAAD DAHLAB de Blida
The objective of this study was to develop alginate/chitosan nanoparticles to deliver model protein drug insulin to protect it from gastric passage,using ionotropic pre-gelation method of an alginate core with calcium chloride followed by chitosan complexation.
The characterization of different properties of prepared nanoparticles, such as particle size, zeta potential value, morphology, stability, structure, and drug loading was studied. The release of insulin from nanoparticles at acidic and alkaline environment was also evaluated. The results indicate thatthe insulin loaded mucoadhesive nanoparticles was a key factor in the improvement of its oral absorption.
Proteins are important therapeutic molecules because they have multiple biological functions; however, the development of a drug-based protein is the origin of many difficulties due to their specific properties and their sensitivity to environmental conditions.
Proteins have low oral and transdermal bioavailability, they are usually administered parenterally. However, most proteins have a very short half-life, requiring frequent injections, which is not well tolerated by patients and may limit the extent of therapies based on protein.
Microencapsulation of peptides and proteins and the preparation of sustained-release forms have been widely studied in order to improve the therapeutic efficacy of these bioactive molecules. However, the difficulties mentioned above concerning the properties of the protein, reduce the choice of an encapsulation process and imposing a strict control of operating conditions to ensure the continued integrity of the protein during all stages of production.
To this end, we propose to use an encapsulation technique based on ionic gelation between two oppositely charged polymers at room temperature polymers at room temperature.
The ionotropic gelation method is very simple and mild. In addition, reversible physical crosslinking by electrostatic interaction insteas of chemical crosslinking avoids the possible toxicity of reagents and other undesirable effects.
The use of polysaccharides and especially natural biopolymers has attracted particular interest due to their desirable biocompatible, biodegradable, hydrophilic and protective properties. In this study, two polysaccharides, alginate and chitosan were used as polyionic polymers to associate with the model protein drug insulin. The use of chitosan in complex with alginate is a promising strategy if we consider the biocompatibility of two polyelectrolytes.
Milling-Induced Changes in Surface Energy and Aspect Ration for Mannitol
Authors: Nektaria Servi1,Majid Naderi1, Raimundo Ho1 Adam Keith2 and Greg Thiele3
1Surface Measureme
nt Systems Ltd., 2125 28th Street SW, Suite 1, Allentown, PA 18103, USA
2Micromeritics Pharmaceutical Services, Norcross, GA, USA
3Micromeritics Analytical Services, Norcross, GA, USA
Contact e-mail
Crystalline materials can be energetically anisotropic, meaning the surface chemistry is not homogeneous or different crystal planes can exhibit different chemistry. Therefore, even for crystalline materials, it is important to treat them as energetically heterogeneous materials, and their surface energy may not be adequately described by a single value. Finite concentration Inverse Gas Chromatography (IGC) experiments allow for the determination of surface energy distributions which more accurately describe the anisotropic surface energy for real materials. Previous studies have investigated the anisotropic nature of mannitol. In this study, we investigate the affects of milling on the heterogeneity of crystalline β D-mannitol. In addition, the particle aspect ratio as a function of milling will be correlated to the surface energy heterogeneity and different crystal planes.
Nanocapsules for Self-Healing Coatings
Dmitry Shchukin
Stephenson Institute for Renewable Energy, University of Liverpool, L69 7ZF, Liverpool, UK
Nanocapsules possessing the ability to release encapsulated corrosion inhibitor in a controlled way can be employed to develop a new family of self-repairing multifunctional coatings for corrosion protection of steel, magnesium and aluminium. The release of the encapsulated inhibitor occurs only when triggered, which prevents leakage of the corrosion inhibitor out of the coating and increases coating durability. This report covers principles and recent developments in the fabrication of the nanocapsules with good compatibility with the coating components, the possibility to encapsulate and upkeep active material, and permeability properties of the shell controlled by external stimuli. The corrosion protection performance is demonstrated employing several commercially available paint formulations as coating matrices for hosting nanocontainers with the use of both laboratory-scale tests (Electrochemical Impedance, SVET) and industrial-scale tests (neutral salt spray tests, weathering tests). Besides the incorporation of the single nanocapsule-inhibitor combination into the coating host, the efficiency of the use of nanocapsule mixtures was demonstrated, especially for different types of the inhibitors.
Hyaluronic acid based nanoparticles encapsulating small RNAs to target cancer cells
A. Tirella1,*, J.M. Rios de la Rosa1, E Lallana-Ozores2, N. Tirelli1,2
1School of Pharmacy, University of Manchester, Oxford Road, M13 9PT, Manchester, UK
2North-West Centre for Advance Drug Delivery (NoWCADD), University of Manchester, Oxford Road, M13 9PT, Manchester, UK
*
Innumerable cases of cancer are diagnosed every day, being responsible for more than 68% of deaths worldwide. Despite the increasing efficacy of treatments and important advances in understanding the molecular basis of the disease, the targeting and delivery of chemotherapeutics is still one of the major issues.
In the context of nucleic acids delivery, an ideal carrier should: 1) be highly targeted i.e. preferentially accumulated in disease tissue, 2) protect the activity of the payloads by limiting their exposure to harmful agents leading to either physical or enzymatic degradation, and 3) release such payloads in the cytoplasm of target cells.
We report here the development of nanoparticles designed to target CD44; which is a membrane protein overexpressed in many tumours, while also being the major receptor of hyaluronic acid (HA) on cell membrane. The described nanoparticles present a positively charged core (chitosan) used to complex with negatively-charged small RNAs sequences e.g. siRNA, miRNA. The HA surface decoration not only promotes the nanoparticle uptake by CD44-expressing cells, but also guarantees nanoparticle stability and payload protection.
To confirm the measured biological effect with the intracellular release of RNAs, the kinetics of uptake and the intracellular localisation of nanoparticles were tracked using fluorescently labeled components i.e. siRNA, chitosan.
Emulsion microgels: a novel approach for delivery of lipophilic molecules
Ophelie Torres, Trang Duong, Shantanu Das, Brent Murray, Anwesha Sarkar
University of Leeds, School of Food Science and Nutrition,
Goodman Fielder Limited, New Zealand
Lipophilic molecules are difficult to deliver in food matrices owing to their limited solubility and rapid oxidation. Furthermore, they pose challenges for site-dependent delivery due to their degradation during physiological transit. Our work addresses these challenges by designing emulsion microges using a facile processing route. The objective of this study was to design and characterize these microgels. This processing route involved three steps: preparation of 20 wt% sunflower oil-in-water emulsion stabilized by whey protein isolate (WPI) (8-10 wt%) using a two-stage valve high pressure homogenizer, protein denaturation by thermal treatment (70-85°C / 5-40 minutes) and then cold ionic gelation by extruding the denatured emulsion through 150-300 µm nozzles into 100 mM CaCl2 using a Buchi Encapsulator®. The resulting soft emulsion microgels were characterized using static light scattering, small deformation rheology in the linear viscoelastic region and microscopy. Emulsion gels prepared using 10 wt% WPI and Ca2+ ions had the typical rheological behaviour of a strong gel (G’ > G”). Microstructural characterization revealed spherical shaped particles. Particle size was influenced by the initial emulsion droplet size, encapsulator nozzle size, denaturation temperature, Ca2+ concentration and emulsion viscosity. These preliminary results show that WPI-based emulsion microgels are potential vehicles for delivering lipophilic molecules.