1,721,006 research outputs found
Recoverable Thermo-Responsive Polymeric Surfactants for the Synthesis of Bulk Plastics from Latexes
Full text linkFree-radical emulsion polymerization (eFRP) is widely adopted in industries due to the great advantages that this technique offers in terms of a high polymerization rate, good heat management, and conduction in a non-toxic solvent like water. On the other hand, eFRP requires surfactants to stabilize the produced polymer nanoparticles (NPs). At the same time, the recovery of a bulk material from a NP suspension needs the addition of salts or alkali for the destabilization of the emulsion and the precipitation of the polymer. These can contaminate the final product and affect its properties. For this reason, alternative strategies able to coagulate the NP latex avoiding the addition of exogenous compounds are needed. In this work, we synthesized thermo-responsive polymeric surfactants that are able to promote the NP formation during the eFRP and to allow the recovery of the bulk polymer by simply increasing the environment temperature. Surfactants with a tunable hydrophilic–lipophilic balance were produced through reversible-addition fragmentation chain transfer (RAFT) emulsion polymerization by chain-extending a polyethylene glycol-based macromolecular chain transfer agent with butyl methacrylate, in order to obtain a series of block copolymers with high blocking efficiency, controlled molecular weight distribution, and well-defined thermo-responsive behavior. Then, the RAFT agent was removed to avoid the further extension of the block copolymers, and the surfactants were tested in the eFRP of different monomers (i.e., butyl methacrylate, methyl methacrylate, and styrene) to produce stable NP latexes. Finally, the possibility of triggering the NP aggregation and of guaranteeing the recovery of both surfactants and bulk material by simply changing the temperature of the system was assessed
Thermo-responsive polymers: Applications of smart materials in drug delivery and tissue engineering
No full textSynthetic polymers are attracting great attention in the last decades for their use in the biomedical field as nanovectors for controlled drug delivery, hydrogels and scaffolds enabling cell growth. Among them, polymers able to respond to environmental stimuli have been recently under growing consideration to impart a “smart” behavior to the final product, which is highly desirable to provide it with a specific dynamic and an advanced function. In particular, thermo-responsive polymers, materials able to undergo a discontinuous phase transition or morphological change in response to a temperature variation, are among the most studied. The development of the so-called controlled radical polymerization techniques has paved the way to a high degree of engineering for the polymer architecture and properties, which in turn brought to a plethora of sophisticated behaviors for these polymers by simply switching the external temperature. These can be exploited in many different fields, from separation to advanced optics and biosensors. The aim of this review is to critically discuss the latest advances in the development of thermo-responsive materials for biomedical applications, including a highly controlled drug delivery, mediation of cell growth and bioseparation. The focus is on the structural and design aspects that are required to exploit such materials for cutting-edge applications in the biomedical field
Integration and digitalization in the manufacturing of therapeutic proteins
No full textThe biopharmaceutical market has experienced a tremendous growth in the last years. However, this growth should be balanced considering the difficulty in bioproduct development and the associated high manufacturing costs. These limitations are pushing towards process intensification, stimulated by the Quality by Design (QbD) initiative. Integrated continuous biomanufacturing has emerged as a promising approach towards high throughputs and reliable product quality attributes. At the same time, to face the increased management complexity and compensate fluctuations at the level of the different unit operations, model-based digitalization stands as a fundamental element. In this review, we discuss the state of the art in integrated biomanufacturing and digitalization to highlight their potential towards process intensification. The continuous technologies adopted in the upstream and downstream processing are first reviewed, with a focus on perfusion bioreactors and continuous chromatography. Then, model-based digitalization and its potential in the monitoring and control of integrated bioprocesses are discussed
Evolution and design of continuous bioreactors for the production of biological products
No full textThe bioprocessing industry is undergoing a crucial change from batch to continuous processes, backed by possible cost reductions and advantages in terms of stable product quality. Initially in this chapter, the concepts related to the birth of biotechnology are brought forward as well as some considerations related to selection of a suitable cell line depending on product type. Then, the three basic process modes for stirred tank bioreactors (i.e., batch, fed-batch and chemostat/CSTR) are exposed, including the mathematical expressions which can be used to model these processes. Perfusion-based continuous bioreactors are introduced as a way for achieving higher cell densities and therefore increasing productivities. Strategies for the development of these processes are explained, including the use of scale-down models. Finally, two case studies are brought forward. Firstly, the extracellular production of monoclonal antibodies, a rapidly expanding class of biopharmaceuticals. Secondly, the production of intracellular products via perfusion is exemplified with the case of bioplastics, specifically polyhydroxyalkanoates, one of the most researched biodegradable biopolymer
Poly(HPMA)-based copolymers with biodegradable side chains able to self assemble into nanoparticles
Full text linkN-(2-Hydroxypropyl)methacrylamide (HPMA) is a water soluble monomer used in the synthesis of
biocompatible and non-immunogenic polymers. In particular, poly(HPMA) can be exploited to sterically
stabilize nanoparticles (NPs) suitable for the delivery of lipophilic therapeutics without the concerns
related to the use of the polyethylene glycol (PEG), such as allergic reactions and the accelerated blood
clearance effect. In addition, the use of the ring opening polymerization (ROP) of a lactone in the
presence of an initiator that bears a double bond and a hydroxyl group is a promising way (the so called
“macromonomer method”) to produce oligoester-based monomers and, in turn, to obtain biodegradable
NPs via free radical polymerization. However, HPMA cannot be used as initiator being a secondary
alcohol and thus hampering the control over the polymer molecular weight (MW). For this reason, in this
work, a novel class of amphiphilic block copolymers that consists of a poly(HPMA) backbone and several
short oligo(3-caprolactone) side chains were produced via the adoption of the reversible addition–
fragmentation chain transfer (RAFT) polymerization and the “inversion” of the macromonomer method.
The oligoester was first synthesized via the ROP of 3-caprolactone in the presence of a primary alcohol
and then attached to HPMA using a succinic acid unit as spacer. The NPs obtained via the self-assembly
of these novel block copolymers are designed to degrade into completely water soluble poly(HPMA)
chains with a MW lower than the threshold value for the renal excretion. The cytotoxicity of these novel
carriers and their ability to load trabectedin, a hydrophobic anticancer therapeutic, were assessed
Influence of the catalytic system on the methanolysis of polyethylene terephthalate at mild conditions: A systematic investigation
Full text linkPlastic disposal is becoming a threat to our environment because of the severe lack of technologies producing high-quality polymers from scraps at a competitive cost compared to the virgin versions. Regarding polyethylene terephthalate (PET), different recycling technologies have been proposed, but they have several disadvantages in terms of cost, process flexibility, and safety. This work systematically investigates the efficiency of different catalytic systems in the methanolysis of PET, operated at mild temperature. High-performance liquid chromatography was adopted to assess the depolymerization efficacy and the product distribution, allowing a quantitative comparison between the different catalytic systems. Potassium carbonate and dichloromethane proved to be the best performing catalyst/cosolvent pair, leading to almost complete depolymerization of PET from bottle flakes and high yield to dimethyl terephthalate. On the other side, when treating PET/cotton fabrics, the hydrolysis catalyzed by hydroxyl groups in the cotton hampered the complete PET depolymerization, leaving room for further research
Health care-associated infections: Controlled delivery of cationic antiseptics from polymeric excipients
Full text linkNowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented
110th Anniversary: Fast and Easy-to-Use Method for Coating Tissue Culture Polystyrene Surfaces with Nonfouling Copolymers to Prevent Cell Adhesion
No full textSynthetic substrates able to prevent the adhesion of cells, commonly referred to as nonfouling surfaces, are useful in a wide range of applications, including the culture of multicellular spheroids and the engineering of complex cell sheets. Nonfouling properties are commonly conferred to surfaces through superhydrophilic polymer-based coatings. At the same time, this type of treatment requires difficult, expensive, and time-consuming procedures, leading to high prices of the final product. In this perspective, the development of quick single-step methods to coat surfaces with nonfouling polymers would dramatically reduce the costs and increase the flexibility of such products. Moreover, this strategy would enable the process to be carried out directly by the end user. In this work, we report a fast and easy-to-use coating method to prevent the nonspecific adhesion of cells on tissue culture polystyrene (TCPS) surfaces. Our approach is based on the adsorption of poly(styrene-co-3-sulfopropyl methacrylate) copolymers comprising nonfouling hydrophilic moieties as well as functionalities that enhance the polymer adhesion to the substrate. The polymer adsorption is obtained from an aqueous mixture with a procedure that can be conveniently performed in short time. The kinetic of polymer adsorption as well as the effect of the polymer concentration was studied in order to reduce the time and cost of the entire procedure. Additionally, the polymer composition and the polymer density were optimized to completely avoid the adhesion of three different adherent cell lines, that is, CHO, A375-P, and HFF-1 cells
Free-radical polymerization of methacrylic acid: From batch to continuous using a stirred tank reactor
Full text linkIn the last years important efforts have been made to convert the traditional batch polymer production to continuous. This transition allows to overcome most of the limitations of discontinuous or semi-continuous processes, such as environmental and safety issues and inadequate product quality. In this work we propose a model–based strategy to convert the solution free-radical polymerization of non-ionized methacrylic acid (MAA) from semibatch to continuous while preserving the product average molecular weight and polymer content. First, a purely kinetic model for the polymerization of MAA was validated for batch, semibatch and continuous stirred tank reactors (CSTR). Then, a basic optimization approach was applied to guide the transition of a selected semibatch process to a CSTR. This strategy results in a substantial productivity increase (5.1 times higher than in the original semibatch) while preserving the selected polymer average molecular weight and dry content. Finally, in order to reduce the residual monomer in the product leaving the CSTR, we simulated the addition of a tubular reactor. This was modelled introducing a small plug flow reactor in series to the CSTR. This approach represents an effective and robust tool for polymer manufacturers to assist switching their productions to continuous preserving their product portfolio
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