Available online at www.sciencedirect.com
ScienceDirect Editorial overview: New technologies: How to put everything you need in a tiny pack and track its delivery? Gleb B Sukhorukov Current Opinion in Pharmacology 2014, 18:vii–ix For a complete overview see the Issue Available online 20th October 2014 http://dx.doi.org/10.1016/j.coph.2014.10.005 1471-4892/# 2014 Published by Elsevier Ltd.
Gleb B Sukhorukov Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary, University of London, Mile End Road, London, E1 4NS, United Kingdom e-mail: [email protected] Gleb Sukhorukov holds a Chair in Biopolymers at School of Engineering and Materials Science, Queen Mary University of London (QMUL). He joined QMUL in 2005 after move from Max Planck Institute of Colloids and Interfaces (Potsdam, Germany). Graduated from the Department of Physics, Lomonosov Moscow State University, he received his Ph.D. degree in 1994 in specialty in biophysics. After postdoctoral positions in academia and industry he won in 2001 the Sofja Kovalevskaja Award of Alexander von Humboldt Foundation to build his own research group at Max Planck Institute. He pioneered research on layer-by-layer assembled polyelectrolyte capsules with most research outcome relevant to development of multifunctional drug delivery systems enabling encapsulation of various substances in capsules of defined size with triggered release induced by light, magnetic field and ultrasound. He is author and coauthor of more than 200 papers and coinventor of 12 patents. His research leadership is reflected on high citations of his works (H-factor 74).
www.sciencedirect.com
Nowadays, the methods of encapsulation have been intensively advanced due to demand in area of biomedicine, biotechnology, pharma and cosmetic industries. Generally, despite of vast methodologies used for microencapsulation of active components there is no unique technology for encapsulation wide class of substances. Each encapsulation method is probably to be specific to what, when and how the active substance is to be enclosed and what capsule materials is used for that. That fact remains wide open the exploration of research approaches from materials science in order to make new capsules with novel, much improved properties to fulfil current requirements. Progress in microencapsulation and nanoencapsulation using physical and chemical methods has been tremendous so far, however, there is still the challenges has come over. In this issue we present how these new challenges could be met and what is recent progress in relatively old encapsulation approaches using block-co-polymers, emulsions, gels and nanoparticulation. First of all, new challenges today in delivery systems is multimodality, i.e. the capsule contains different substances or functions and can be smart enough to navigate and/or response to different factors of surrounding media including external physical addressing and any sort of interrogation with remote devices. Ideally the capsule should deliver something upon local environmental request or external signalling and then degrade or leave once ‘their mission is done’. Is it realistic scenario and what modern material science can offer to do that? In order to tackle this challenge various functionality have to be tailored in one entity of capsule. Another challenge in microencapsulation remains once delivery to biological cells and tissues is concerned is capsule compatibility and biodegradability. From this aspect the use of polymers already approved for clinical studies for capsule composition paves a solid way to applications. At this aspect Layer-byLayer assembly has also advantage as it can utilize the wide range of polymers including those with intensively studied compatibility and degradation. It is main advantage of this technology as it avoids chemical modifications. In this issue we illustrate the advances of LbL encapsulation approaches in areas of multifunctional capsule construct fabrication of various size and shape, controlled permeability, various responsiveness, behaviour in biological media. Shchukin and Shchukina review opportunities of LbL assembly method for capsule fabrication in terms to tailor different functions and responsiveness to carriers with encapsulated cargo. Apart of widely used charge alternation during LbL deposition of charged species including synthetic and natural polyelectrolyte, proteins and functional nanoparticles the hydrogen bounding, chemical reaction, hydrogen bounding and stereometric complexes have been applied to construct Current Opinion in Pharmacology 2014, 18:vii–ix
viii
New technologies
capsules with defined permeability and responsiveness to pH, temperature, light, magnetic field and enzymatic degradation. Skirtach et al. emphasize the biological applications of multifunctional LbL assembled capsules and capsule interaction with cells and light controlled intracellular trafficking of released cargo while capsules are in biological media. Other stimuli such as mechanic, ultrasound as well as multicompartmental capsules with are also considered in the review. Compatibility plays a key role when coating of entire living cells is under consideration. Fakhrullin et al. describe recent advances on encapsulating living cells aiming to bring resistance for aggressive external factors as well as responsiveness to remote addressing, for instance such as magnetic field. In this review various ways of cell encapsulation and labelling are reviewed. LbL method is proposed as one of most suitable for cell to tolerate its surface modification while the capsule shell is assembled. Incorporation of Magnetic nanoparticles (MNP) in shell can make single biological cells as well as entire LbL encapsulated organisms such as worms to be navigated with magnetic field. Cells encapsulation in inorganic or composite organic/inorganic shell might be realised via cell surface template chemical reaction at the mind condition for cell survival. Considering encapsulation, ones often consider the capsules as round shaped and existing mostly in spherical forms. Indeed, most of the encapsulation techniques based on emulsions, dropping or spray produced spherical capsules. However, exploitation of LbL approach in forming few nanometer thin coating on various surface leads to stable encapsulation of irregular shaped particles or drug crystal and participates of hundred nanometer size. Lvov and colleagues illustrate this approach in encapsulation of single spherical and tubular particles of 50–150 nm in diameter and loaded with drug. The major challenge in such formulation is high particles aggregation coating while aiming required therapeutic dosed of 2–3 mg/mL. The review pays particular attention in proper selection of surface properties of polymers to enable steric stabilisation of nanoparticles. Alternation of PEG derived charged polymers is found to be a good solution to overcome problematic issue of high dose form stability. Direct assembling of shell on drug particulates one can route away from using emulsion and other solvents as intermediate steps in formulation. Nanocarriers remain hot topic in delivery of pharmaceuticals. Ryan and Brayden discuss current state in nanoparticle based developments in relation to cancer and product which either in clinical trial or already approved for practical use as medicine. Various nanoparticles constructs differed by their chemical nature, therapeutic and imaging properties, both targeted and non-targeted are Current Opinion in Pharmacology 2014, 18:vii–ix
discussed in light of their advantages, perspective, challenges and obstacles on their way for clinical use. Apart of magnetically driven navigation of capsules where MNP are used as building blocks to ensure enough susceptibility of entire capsule constructs the other important use of MNP is contrast agents for Magnetic Resonance Imaging. In order to ensure biomedical compatibility, stability in media, long circulation and adequate imaging capacity these MNP have to be encapsulated. Ai et al. describe different methods of surface properties engineering of MNP. Clinical trials with MNPs and these perspective in imaging as well as Therapy using MNP as carriers are also discussed in this review. Current research on MNPs illustrates that new challenges in encapsulation are relevant not only to store, protection and delivery for therapeutic purposes, but also for sensing and diagnostics. So-called ‘Theranostic’ systems can benefit from novel technologies in encapsulation. Sensing elements can be complex and include number of different molecules to be co-localised. Such systems are to be protected, i.e. encapsulated. Alternatively, capsule fabrication approaches provide a tool for increasing sensitivity via confined geometry. In this issue we present two reviews on sensing aspect of encapsulation technologies. Parak et al. describe use of particles and capsules with encapsulated fluorophors to specific quantification pH, ion concentration and prospective other metabolites in biological media including exploring interior of living cells. Co-encapsulation of more than one sensitive fluorophors or combination of enzyme and fluorophor in one capsules paves away to unambiguous quantitative in situ monitoring of biological cells with optically based recording. Gorin et al.1 discuss application of Surface Enhanced Raman Scattering (SERS) for analysis of pharmaceuticals. A key factor in enhanced resolution of SERS platform is combination on close proximity of analyte and so-called ‘hot spots’ with high sensitivity to Raman signalling which are represented with shaped gold or silver nanoparticles. Reviewing several approaches with SERS platform fabrication the review demonstrates use of LbL assembly to for SERS based monitoring inside biological media as well as discusses perspectives on fabrication of SERS platform with feedback principals where release of bioactives could be triggered as response to sensing outcome. This issue reviews progress in already established methods of encapsulation. Self-assembly of block-copolymers has been intensively used for entrapping and delivery for decades. New developments in the area are associated with ways how to entrapped molecules in these 1
The paper by Gorin et al. has been handled by David G Trist, Editor. www.sciencedirect.com
Editorial overview Sukhorukov ix
capsules and triggering cargo release. Battaglia et al. review recent advances in this area including post-preparation loading of polymersomes via electroporation and time specific release using tuneable cross-linker density.
of variable size and shape using electrospinning and electrospraying have been reviewed by Edirisinghe et al. These EHD principals could be combined with microfluidics processes to fabricate microbubbles at various size scales.
Kakran and Antipina review new developments on widely used emulsification approach for encapsulation. Novel insights in long ago established methods are production of emulgels where emulsion suspension is used in solidlike phase what facilitate its exploitation as stable and durable solid like system combining properties of both hydrogels and emulsions. Another tuning of emulsion based encapsulation could be brought by mentioned above LbL coating of polymers and proteins in order to stabilise and protect emulsion droplets, for instance against oxidation. Particular attention in this review is addressed to current requirements on emulsion based encapsulation in Biomedical, Food and Personal care sectors of applications.
Active substances can be packaged in microcontainers at surfaces. Kiryukhin describes novel approach of fabrication of arrays of enclosed chambers produced by imprinting followed up by thin film assembly over modulated surface. The produced well can be filled with substances of interest and later sealed with films. Incorporation of functional polymers or nanoparticles makes these microchambers responsive to external triggering such as light leading to container rupture and site specific release of active component. This novel technology envisages application in implant coating and other biomedical device where site and time specific release is demanding.
Physical approaches for microencapsulation have been reviewed in two sections. Microfluidic technology to produce double emulsions using devices with co-flow geometry is described by Chu et al. Combination of oil and water-based liquid flows in microfluidics results on capsule fabrication with defined size and payload. Controlled manipulation of emulsion droplets gives unique opportunity for pharmacology to dosage amount of active components in each capsule. Application of electrohydrodynamics (EHD) for production of capsule
Thus, these novel approaches in encapsulation and micropackaging presented in this issue give an overview on how diverse modern methods of polymer and physical chemistry could contribute to design delivery and microsized sensing systems to make them ‘a la carte’ functional and externally addressable. Keeping everything one needs in one tiny backpack and ship it while tracking its delivery becomes a realistic task and could be brought to you by modern advances of Materials Science in microfabrication and nanofabrication.
www.sciencedirect.com
Current Opinion in Pharmacology 2014, 18:vii–ix
ScienceDirect Editorial overview: New technologies: How to put everything you need in a tiny pack and track its delivery? Gleb B Sukhorukov Current Opinion in Pharmacology 2014, 18:vii–ix For a complete overview see the Issue Available online 20th October 2014 http://dx.doi.org/10.1016/j.coph.2014.10.005 1471-4892/# 2014 Published by Elsevier Ltd.
Gleb B Sukhorukov Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary, University of London, Mile End Road, London, E1 4NS, United Kingdom e-mail: [email protected] Gleb Sukhorukov holds a Chair in Biopolymers at School of Engineering and Materials Science, Queen Mary University of London (QMUL). He joined QMUL in 2005 after move from Max Planck Institute of Colloids and Interfaces (Potsdam, Germany). Graduated from the Department of Physics, Lomonosov Moscow State University, he received his Ph.D. degree in 1994 in specialty in biophysics. After postdoctoral positions in academia and industry he won in 2001 the Sofja Kovalevskaja Award of Alexander von Humboldt Foundation to build his own research group at Max Planck Institute. He pioneered research on layer-by-layer assembled polyelectrolyte capsules with most research outcome relevant to development of multifunctional drug delivery systems enabling encapsulation of various substances in capsules of defined size with triggered release induced by light, magnetic field and ultrasound. He is author and coauthor of more than 200 papers and coinventor of 12 patents. His research leadership is reflected on high citations of his works (H-factor 74).
www.sciencedirect.com
Nowadays, the methods of encapsulation have been intensively advanced due to demand in area of biomedicine, biotechnology, pharma and cosmetic industries. Generally, despite of vast methodologies used for microencapsulation of active components there is no unique technology for encapsulation wide class of substances. Each encapsulation method is probably to be specific to what, when and how the active substance is to be enclosed and what capsule materials is used for that. That fact remains wide open the exploration of research approaches from materials science in order to make new capsules with novel, much improved properties to fulfil current requirements. Progress in microencapsulation and nanoencapsulation using physical and chemical methods has been tremendous so far, however, there is still the challenges has come over. In this issue we present how these new challenges could be met and what is recent progress in relatively old encapsulation approaches using block-co-polymers, emulsions, gels and nanoparticulation. First of all, new challenges today in delivery systems is multimodality, i.e. the capsule contains different substances or functions and can be smart enough to navigate and/or response to different factors of surrounding media including external physical addressing and any sort of interrogation with remote devices. Ideally the capsule should deliver something upon local environmental request or external signalling and then degrade or leave once ‘their mission is done’. Is it realistic scenario and what modern material science can offer to do that? In order to tackle this challenge various functionality have to be tailored in one entity of capsule. Another challenge in microencapsulation remains once delivery to biological cells and tissues is concerned is capsule compatibility and biodegradability. From this aspect the use of polymers already approved for clinical studies for capsule composition paves a solid way to applications. At this aspect Layer-byLayer assembly has also advantage as it can utilize the wide range of polymers including those with intensively studied compatibility and degradation. It is main advantage of this technology as it avoids chemical modifications. In this issue we illustrate the advances of LbL encapsulation approaches in areas of multifunctional capsule construct fabrication of various size and shape, controlled permeability, various responsiveness, behaviour in biological media. Shchukin and Shchukina review opportunities of LbL assembly method for capsule fabrication in terms to tailor different functions and responsiveness to carriers with encapsulated cargo. Apart of widely used charge alternation during LbL deposition of charged species including synthetic and natural polyelectrolyte, proteins and functional nanoparticles the hydrogen bounding, chemical reaction, hydrogen bounding and stereometric complexes have been applied to construct Current Opinion in Pharmacology 2014, 18:vii–ix
viii
New technologies
capsules with defined permeability and responsiveness to pH, temperature, light, magnetic field and enzymatic degradation. Skirtach et al. emphasize the biological applications of multifunctional LbL assembled capsules and capsule interaction with cells and light controlled intracellular trafficking of released cargo while capsules are in biological media. Other stimuli such as mechanic, ultrasound as well as multicompartmental capsules with are also considered in the review. Compatibility plays a key role when coating of entire living cells is under consideration. Fakhrullin et al. describe recent advances on encapsulating living cells aiming to bring resistance for aggressive external factors as well as responsiveness to remote addressing, for instance such as magnetic field. In this review various ways of cell encapsulation and labelling are reviewed. LbL method is proposed as one of most suitable for cell to tolerate its surface modification while the capsule shell is assembled. Incorporation of Magnetic nanoparticles (MNP) in shell can make single biological cells as well as entire LbL encapsulated organisms such as worms to be navigated with magnetic field. Cells encapsulation in inorganic or composite organic/inorganic shell might be realised via cell surface template chemical reaction at the mind condition for cell survival. Considering encapsulation, ones often consider the capsules as round shaped and existing mostly in spherical forms. Indeed, most of the encapsulation techniques based on emulsions, dropping or spray produced spherical capsules. However, exploitation of LbL approach in forming few nanometer thin coating on various surface leads to stable encapsulation of irregular shaped particles or drug crystal and participates of hundred nanometer size. Lvov and colleagues illustrate this approach in encapsulation of single spherical and tubular particles of 50–150 nm in diameter and loaded with drug. The major challenge in such formulation is high particles aggregation coating while aiming required therapeutic dosed of 2–3 mg/mL. The review pays particular attention in proper selection of surface properties of polymers to enable steric stabilisation of nanoparticles. Alternation of PEG derived charged polymers is found to be a good solution to overcome problematic issue of high dose form stability. Direct assembling of shell on drug particulates one can route away from using emulsion and other solvents as intermediate steps in formulation. Nanocarriers remain hot topic in delivery of pharmaceuticals. Ryan and Brayden discuss current state in nanoparticle based developments in relation to cancer and product which either in clinical trial or already approved for practical use as medicine. Various nanoparticles constructs differed by their chemical nature, therapeutic and imaging properties, both targeted and non-targeted are Current Opinion in Pharmacology 2014, 18:vii–ix
discussed in light of their advantages, perspective, challenges and obstacles on their way for clinical use. Apart of magnetically driven navigation of capsules where MNP are used as building blocks to ensure enough susceptibility of entire capsule constructs the other important use of MNP is contrast agents for Magnetic Resonance Imaging. In order to ensure biomedical compatibility, stability in media, long circulation and adequate imaging capacity these MNP have to be encapsulated. Ai et al. describe different methods of surface properties engineering of MNP. Clinical trials with MNPs and these perspective in imaging as well as Therapy using MNP as carriers are also discussed in this review. Current research on MNPs illustrates that new challenges in encapsulation are relevant not only to store, protection and delivery for therapeutic purposes, but also for sensing and diagnostics. So-called ‘Theranostic’ systems can benefit from novel technologies in encapsulation. Sensing elements can be complex and include number of different molecules to be co-localised. Such systems are to be protected, i.e. encapsulated. Alternatively, capsule fabrication approaches provide a tool for increasing sensitivity via confined geometry. In this issue we present two reviews on sensing aspect of encapsulation technologies. Parak et al. describe use of particles and capsules with encapsulated fluorophors to specific quantification pH, ion concentration and prospective other metabolites in biological media including exploring interior of living cells. Co-encapsulation of more than one sensitive fluorophors or combination of enzyme and fluorophor in one capsules paves away to unambiguous quantitative in situ monitoring of biological cells with optically based recording. Gorin et al.1 discuss application of Surface Enhanced Raman Scattering (SERS) for analysis of pharmaceuticals. A key factor in enhanced resolution of SERS platform is combination on close proximity of analyte and so-called ‘hot spots’ with high sensitivity to Raman signalling which are represented with shaped gold or silver nanoparticles. Reviewing several approaches with SERS platform fabrication the review demonstrates use of LbL assembly to for SERS based monitoring inside biological media as well as discusses perspectives on fabrication of SERS platform with feedback principals where release of bioactives could be triggered as response to sensing outcome. This issue reviews progress in already established methods of encapsulation. Self-assembly of block-copolymers has been intensively used for entrapping and delivery for decades. New developments in the area are associated with ways how to entrapped molecules in these 1
The paper by Gorin et al. has been handled by David G Trist, Editor. www.sciencedirect.com
Editorial overview Sukhorukov ix
capsules and triggering cargo release. Battaglia et al. review recent advances in this area including post-preparation loading of polymersomes via electroporation and time specific release using tuneable cross-linker density.
of variable size and shape using electrospinning and electrospraying have been reviewed by Edirisinghe et al. These EHD principals could be combined with microfluidics processes to fabricate microbubbles at various size scales.
Kakran and Antipina review new developments on widely used emulsification approach for encapsulation. Novel insights in long ago established methods are production of emulgels where emulsion suspension is used in solidlike phase what facilitate its exploitation as stable and durable solid like system combining properties of both hydrogels and emulsions. Another tuning of emulsion based encapsulation could be brought by mentioned above LbL coating of polymers and proteins in order to stabilise and protect emulsion droplets, for instance against oxidation. Particular attention in this review is addressed to current requirements on emulsion based encapsulation in Biomedical, Food and Personal care sectors of applications.
Active substances can be packaged in microcontainers at surfaces. Kiryukhin describes novel approach of fabrication of arrays of enclosed chambers produced by imprinting followed up by thin film assembly over modulated surface. The produced well can be filled with substances of interest and later sealed with films. Incorporation of functional polymers or nanoparticles makes these microchambers responsive to external triggering such as light leading to container rupture and site specific release of active component. This novel technology envisages application in implant coating and other biomedical device where site and time specific release is demanding.
Physical approaches for microencapsulation have been reviewed in two sections. Microfluidic technology to produce double emulsions using devices with co-flow geometry is described by Chu et al. Combination of oil and water-based liquid flows in microfluidics results on capsule fabrication with defined size and payload. Controlled manipulation of emulsion droplets gives unique opportunity for pharmacology to dosage amount of active components in each capsule. Application of electrohydrodynamics (EHD) for production of capsule
Thus, these novel approaches in encapsulation and micropackaging presented in this issue give an overview on how diverse modern methods of polymer and physical chemistry could contribute to design delivery and microsized sensing systems to make them ‘a la carte’ functional and externally addressable. Keeping everything one needs in one tiny backpack and ship it while tracking its delivery becomes a realistic task and could be brought to you by modern advances of Materials Science in microfabrication and nanofabrication.
www.sciencedirect.com
Current Opinion in Pharmacology 2014, 18:vii–ix
