227 research outputs found
Biodegradation-resistant multilayers coated with gold nanoparticles. Toward a tailor-made artificial extracellular matrix
Polymer multicomponent coatings such as multilayers mimic extracellular matrix (ECM) that attracts significant attention for their use as functional supports for advanced cell culture and tissue engineering. Herein, biodegradation and molecular transport in hyaluronan/polylysine multilayers coated with gold nanoparticles was described. Nanoparticle coating acts as semipermeable barrier that governs molecular transport into/from the multilayers and makes them biodegradation resistant. Model protein lysozyme (mimics of ECM soluble signals) diffuses in the multilayers as fast and slow diffusing populations existing in an equilibrium. Such composite system may have high potential to be exploited as degradation-resistant drug delivery platforms suitable for cell-based applications. The extracellular matrix (ECM) provides not only a structural support for cell-based applications
Hybrids of polymer multilayers, lipids, and nanoparticles: mimicking the cellular microenvironment
Here we address research directions and trends developed following novel concepts in 2D/3D self-assembled polymer structures established in the department led by Helmuth Möhwald. These functional structures made of hybrids of polymer multilayers, lipids, and nanoparticles stimulated research in the design of the cellular microenvironment. The composition of the extracellular matrix (ECM) and dynamics of biofactor presentation in the ECM can be recapitulated by the hybrids. Proteins serve as models for protein-based biofactors such as growth factors, cytokines, hormones, and so forth. A fundamental understanding of complex intermolecular interactions and approaches developed for the externally IR-light-triggered release offers a powerful tool for controlling the biofactor presentation. Pure protein beads made via a mild templating on vaterite CaCO3 crystals can mimic cellular organelles in terms of the compartmentalization of active proteins. We believe that an integration of the approaches developed and described here offers a strong tool for engineering and mimicking both extra- and intracellular microenvironments
Hybrids of polymeric capsules, lipids, and nanoparticles: thermodynamics and temperature rise at the nanoscale and emerging applications
The importance of thermodynamics does not need to be emphasized. Indeed, elevated temperature processes govern not only industrial scale production, but also self-assembly, chemical reaction, interaction between molecules, etc. Not surprisingly, biological processes take typically place at defined temperature. Here, we look at possibilities to raise the localized temperature by a laser around noble metal nanoparticles incorporated into shells of layer-bylayer (LbL) polyelectrolyte microcapsules â freely suspended delivery vehicles in aqueous solution, developed in the Department of Interfaces, Max-Planck Institute of Colloids and Interfaces headed by Helmuth Möhwald. Understanding the mechanisms around localized temperature rise is essential, that is why we analyze thermodynamics at the nanoscale, the influence of incident intensity, nanoparticle size, their distribution and aggregation state. This leads us to scrutinize "global" (used for thermal encapsulation) versus "local" (used for release of encapsulated materials) temperature around nanoparticles. Similar analysis is extended to the lipid membrane system of vesicles and cells, on which nanoparticles are adsorbed. Insights are provided into the mechanisms of physico-chemical and biological effects, the nature of which has always been profoundly, interactively, and engagingly discussed in the Department. This analysis is combined with recent developments providing outlook and highlighting a broad range of emerging applications
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Naturally derived nano- and micro-drug delivery vehicles: halloysite, vaterite and nanocellulose
Recent advances in drug delivery and controlled release had a great impact on bioscience, medicine and tissue engineering. Consequently, a variety of advanced drug delivery vehicles either have already reached the market or are approaching the phase of commercial production. Progressive growth of the drug delivery market has led to the necessity to earnestly concern about economically viable, up-scalable and sustainable technologies for a large-scale production of drug delivery carriers. We have identified three attractive natural sources of drug carriers: aluminosilicate clays, minerals of calcium carbonate, and cellulose. Three classes of drug delivery carriers derived from these natural materials are halloysite nanotubes, vaterite crystals and nanocellulose. These carriers can be produced using âgreenâ technologies from some of the most abundant sources on the Earth and have extremely high potential to meet all criteria applied for the manufacture of modern delivery carriers. We provide an up-to-date snapshot of these drug delivery vehicles towards their use for bioapplications, in particular for drug delivery and tissue engineering. The following research topics are addressed: (i) the availability, sources and methodologies used for production of these drug delivery vehicles, (ii) the drug loading and release mechanisms of these delivery vehicles, (iii) in vitro, in vivo, and clinical studies on these vehicles, and (iv) employment of these vehicles for tissue engineering. Finally, the prospects for vehiclesâ further development and industrialisation are critically assessed, highlighting most attractive future research directions such as the design of third generation active biomaterials
Binding mechanism of the model charged dye carboxyfluorescein to hyaluronan/polylysine multilayers
Biopolymer-based multilayers become more and more attractive due to the vast span of biological application they can be used for, e.g., implant coatings, cell culture supports, scaffolds. Multilayers have demonstrated superior capability to store enormous amounts of small charged molecules, such as drugs, and release them in a controlled manner; however, the binding mechanism for drug loading into the multilayers is still poorly understood. Here we focus on this mechanism using model hyaluronan/polylysine (HA/PLL) multilayers and a model charged dye, carboxyfluorescein (CF). We found that CF reaches a concentration of 13 mM in the multilayers that by far exceeds its solubility in water. The high loading is not related to the aggregation of CF in the multilayers. In the multilayers, CF molecules bind to free amino groups of PLL; however, intermolecular CFâCF interactions also play a role and (i) endow the binding with a cooperative nature and (ii) result in polyadsorption of CF molecules, as proven by fitting of the adsorption isotherm using the BET model. Analysis of CF mobility in the multilayers by fluorescence recovery after photobleaching has revealed that CF diffusion in the multilayers is likely a result of both jumping of CF molecules from one amino group to another and movement, together with a PLL chain being bound to it. We believe that this study may help in the design of tailor-made multilayers that act as advanced drug delivery platfor
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Release from polyelectrolyte multilayer capsules in solution and on polymeric surfaces
Release from polyelectrolyte multilayer microcapsules represents one of the most important steps enabling practical use of the microcapsules. A number of biological and non-biological applications are envisaged by proper encapsulation of molecules of interest and their release performance. Since the invention of the microcapsules at the Max-Planck Institute of Colloids and Interfaces in 1998 the work towards microcapsule assistant release has undergone tremendous progress. Almost simultaneously with development of release approaches an extensive base of applications has been advanced. In this progress report the release from the capsules in a solution and those immobilized on the surface of polymeric films is addressed
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Inter-protein interactions govern protein loading into porous vaterite CaCO3 crystals
The fast development of protein therapeutics has resulted in a high demand for advanced delivery carriers that can effectively host therapeutic proteins, preserve their bioactivity and release them on demand. Accordingly, vaterite CaCO3 crystals have attracted special attention as sacrificial templates for protein encapsulation in micro- and nanoparticles (capsules and beads, respectively) under mild biofriendly conditions. This study aimed to better understand the mechanism of protein loading into crystals as a primary step for protein encapsulation. The loading of three therapeutic proteins (250 kDa catalase, 5.8 kDa insulin, and 6.5 kDa aprotinin) was investigated for crystals with different porosities. However, unexpectedly, the protein loading capacity was not consistent with the protein molecular weight. It solely depends on the inter-protein interactions in the bulk solution in the presence of crystals and that inside the crystals. The smallest protein aprotinin aggregates in the bulk (its aggregate size is about 100 nm), which prohibits its loading into the crystals. Insulin forms hexamers in the bulk, which can diffuse into the crystal pores but tend to aggregate inside the pores, suppressing protein diffusion inward. Catalase, the largest protein tested, does not form any aggregates in the bulk and diffuses freely into the crystals; however, its diffusion into small pores is sterically restricted. These findings are essential for the encapsulation of protein therapeutics by means of templating based on CaCO3 crystals and for the engineering of protein-containing microparticles having desired architectures
The mechanism of catalase loading into porous vaterite CaCO3 crystals by co-synthesis
Porous vaterite CaCO3 crystals are nowadays extensively used as high-capacity bio-friendly sacrificial templates for the fabrication of such protein-containing nano- and micro-particles as capsules and beads. The first step in the protein encapsulation is performed through loading of the protein molecules into the crystals. Co-synthesis is one of the most useful and simple methods proven to effectively load crystals with proteins; however, the loading mechanism is still unknown. To understand the mechanism, in this study, we focus on the loading of a model protein catalase into the crystals by means of adsorption into pre-formed crystals (ADS) and co-synthesis (COS). Analysis of the physico-chemical characteristics of the protein in solution and during the loading and simulation of the protein packing into the crystals are performed. COS provides more effective loading than ADS giving protein contents in the crystals of 20.3 and 3.5 w/w%, respectively. Extremely high loading for COS providing a local protein concentration of about 550 mg mLâ1 is explained by intermolecular protein interactions, i.e. formation of protein aggregates induced by CaCl2 during the co-synthesis. This is supported by a lower equilibrium constant obtained for COS (5 Ă 105 Mâ1) than for ADS (23 Ă 105 Mâ1), indicating a higher affinity of single protein molecules rather than aggregates to the crystal surface. Fitting the adsorption isotherms by classical adsorption models has shown that the Langmuir and BET models describe the adsorption phenomenon better than the Freundlich model, proving the aggregation in solution followed by adsorption of the aggregates into the crystals. We believe that this study will be useful for protein encapsulation through CaCO3 crystals using the COS method
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Porous alginate scaffolds assembled using vaterite CaCO3 crystals
Formulation of multifunctional biopolymer-based scaffolds is one of the major focuses in modern tissue engineering and regenerative medicine. Besides proper mechanical/chemical properties, an ideal scaffold should: (i) possess a well-tuned porous internal structure for cell seeding/growth and (ii) host bioactive molecules to be protected against biodegradation and presented to cells when required. Alginate hydrogels were extensively developed to serve as scaffolds, and recent advances in the hydrogel formulation demonstrate their applicability as âidealâ soft scaffolds. This review focuses on advanced porous alginate scaffolds (PAS) fabricated using hard templating on vaterite CaCO3 crystals. These novel tailor-made soft structures can be prepared at physiologically relevant conditions offering a high level of control over their internal structure and high performance for loading/release of bioactive macromolecules. The novel approach to assemble PAS is compared with traditional methods used for fabrication of porous alginate hydrogels. Finally, future perspectives and applications of PAS for advanced cell culture, tissue engineering, and drug testing are discussed
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PNIPAM coated biopolymer multilayers for temperature-mediated drug release
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