| 1. |
- Edlund, Ulrica, et al.
(author)
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Polyesters based on diacid monomers
- 2003
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In: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 55:4, s. 585-609
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Research review (peer-reviewed)abstract
- Polymers with ester linkages in their main chain comprise a family of polymers with immense diversity and versatility. This review deals with the preparation of such polymers from dicarboxylic acid monomers, and the result in terms of properties and applicability. Polyesters alone, and their copolymers with amides, anhydrides, urethanes, imides, ethers or other functional groups, offer countless opportunities to tune the properties of the resulting material within a broad range. Of particular interest is the inherent biodegradability of the ester linkage. Biodegradability is sought after in a wide range of applications, above all in the preparation of environmentally friendly polymers and biomedical materials for temporary surgical use and in drug delivery.
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| 2. |
- Albertsson, Ann-Christine, et al.
(author)
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Recent developments in enzyme-catalyzed ring-opening polymerization
- 2008
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In: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 60:9, s. 1077-1093
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Research review (peer-reviewed)abstract
- An exponential growth has been observed in the last decade where enzymes were used as catalysts for polymerization of different monomers and due to enzyme's origin from natural sources they have been taken as a substitute for the metal-based catalytic systems. Mild polymerization conditions, high enantio- and regio-selectivity and recyclability of enzymes give them an extra edge over the use of organo-metallic catallysts. Though the enzyme-catalyzed polymerizations are environmentally highly advantageous, the high cost, large quantity of enzymes required for polymerization and formation of relatively low molecular weight polymers obstruct their employment in the industry. Due to these reasons, this technique is still at die stage of infancy to generate polymeric materials which can be converted to any useful physical form. In this article enzyme-catalyzed ring-opening polymerization of lactones, lactides, cyclic carbonates and depsipeptides has been reviewed with special focus on the molecular weight of the polymers synthesized hitherto using enzyme catalysis. It is necessary to obtain polymers of sufficient molecular weight from enzyme catalysis to withstand the specific requirements of their end applications if this technique is desired to be escalated to commercial level.
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| 3. |
- Artursson, Per, et al.
(author)
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Caco-2 monolayers in experimental and theoretical predictions of drug transport
- 2012
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In: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 64:S, s. 280-289
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Research review (peer-reviewed)abstract
- This review examines the use of Caco-2 monolayers in the prediction of intestinal drug absorption. First, the different routes of drug transport in Caco-2 monolayers are compared with those seen in vivo. Second, the prediction of drug absorption in vivo from transport experiments in cell monolayers is discussed for different classes of drugs. Finally, the use of Caco-2 monolayers as a reference model in physico-chemical and theoretical predictions of drug absorption is discussed. We conclude that Caco-2 monolayers can be used to identify drugs with potential absorption problems, and possibly also to select drugs with optimal passive absorption characteristics from series of pharmacologically active molecules generated in drug discovery programs.
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| 4. |
- Bergström, Christel A. S., et al.
(author)
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Computational prediction of formulation strategies for beyond-rule-of-5 compounds
- 2016
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In: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 101, s. 6-21
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Research review (peer-reviewed)abstract
- The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity. These physicochemical properties move the compounds towards beyond rule-of-5 (B-r-o-5) chemical space and often result in lower water solubility. For such B-r-o-5 compounds non-traditional delivery strategies (i.e. those other than conventional tablet and capsule formulations) typically are required to achieve adequate exposure after oral administration. In this review, we present the current status of computational tools for prediction of intestinal drug absorption, models for prediction of the most suitable formulation strategies for B-r-o-5 compounds and models to obtain an enhanced understanding of the interplay between drug, formulation and physiological environment. In silico models are able to identify the likely molecular basis for low solubility in physiologically relevant fluids such as gastric and intestinal fluids. With this baseline information, a formulation scientist can, at an early stage, evaluate different orally administered, enabling formulation strategies. Recent computational models have emerged that predict glass-forming ability and crystallisation tendency and therefore the potential utility of amorphous solid dispersion formulations. Further, computational models of loading capacity in lipids, and therefore the potential for formulation as a lipid-based formulation, are now available. Whilst such tools are useful for rapid identification of suitable formulation strategies, they do not reveal drug localisation and molecular interaction patterns between drug and excipients. For the latter, Molecular Dynamics simulations provide an insight into the interplay between drug, formulation and intestinal fluid. These different computational approaches are reviewed. Additionally, we analyse the molecular requirements of different targets, since these can provide an early signal that enabling formulation strategies will be required. Based on the analysis we conclude that computational biopharmaceutical profiling can be used to identify where non-conventional gateways, such as prediction of 'formulate-ability' during lead optimisation and early development stages, are important and may ultimately increase the number of orally tractable contemporary targets.
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| 5. |
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| 6. |
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| 7. |
- Bysell, Helena, et al.
(author)
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Microgels and microcapsules in peptide and protein drug delivery
- 2011
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In: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 63:13, s. 1172-1185
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Research review (peer-reviewed)abstract
- The present review focuses on the interaction of microgels and microcapsules with biological macromolecules, particularly peptides and proteins, as well as drug delivery applications of such systems. Results from recent studies on factors affecting peptide/protein binding to, and release from, microgels and related systems are discussed, including effects of network properties, as well as protein aggregation, peptide length, hydrophobicity and charge (distributions), secondary structure, and cyclization. Effects of ambient conditions (pH, ionic strength, temperature, etc.) are also discussed, all with focus on factors of importance for the performance of microgel and microcapsule delivery systems for biomacromolecular drugs.
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| 8. |
- Colombo, Stefano, et al.
(author)
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Transforming nanomedicine manufacturing toward Quality by Design and microfluidics
- 2018
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In: Advanced Drug Delivery Reviews. - : Elsevier. - 0169-409X .- 1872-8294. ; 128, s. 115-131
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Research review (peer-reviewed)abstract
- Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doi ng so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field. (C) 2018 Elsevier B.V. All rights reserved.
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| 9. |
- Daly, Norelle, et al.
(author)
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Discovery, structure and biological activities of cyclotides
- 2009
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In: Advanced Drug Delivery Reviews. - : Advanced Drug Delivery Reviews. - 0169-409X .- 1872-8294. ; 61, s. 918-930
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Research review (other academic/artistic)abstract
- Cyclotides are small disulfide-rich peptides that are characterized by a head-to-tail cyclized peptide backbone and a knotted arrangement of three conserved disulfide bonds. They are present in many plants from the Violaceae, Rubiaceae and Cucurbitaceae families, with individual plants expressing a suite of dozens of cyclotides. So far > 140 sequences and 15 three-dimensional structures have been determined but it is estimated that the family probably comprises many thousands of members. Their primary function in plants is thought to be as defense agents, based on their potent insecticidal activity, but they also have a range of other biological activities, including anti-HIV, antimicrobial and cytotoxic activities. Because of their exceptional stability they have attracted interest as templates for protein engineering and drug design applications. This article gives an overview of the discovery of cyclotides, describes their unique structural features and range of bioactivities, and discusses their applications in drug design.
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| 10. |
- de la Rica, Roberto, et al.
(author)
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Enzyme-responsive nanoparticles for drug release and diagnostics
- 2012
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In: Advanced Drug Delivery Reviews. - : Elsevier. - 0169-409X .- 1872-8294. ; 64:11, s. 967-978
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Research review (peer-reviewed)abstract
- Enzymes are key components of the bionanotechnology toolbox that possess exceptional biorecognition capabilities and outstanding catalytic properties. When combined with the unique physical properties of nanomaterials, the resulting enzyme-responsive nanoparticles can be designed to perform functions efficiently and with high specificity for the triggering stimulus. This powerful concept has been successfully applied to the fabrication of drug delivery schemes where the tissue of interest is targeted via release of cargo triggered by the biocatalytic action of an enzyme. Moreover, the chemical transformation of the carrier by the enzyme can also generate therapeutic molecules, therefore paving the way to design multimodal nanomedicines with synergistic effects. Dysregulation of enzymatic activity has been observed in a number of severe pathological conditions, and this observation is useful not only to program drug delivery in vivo but also to fabricate ultrasensitive sensors for diagnosing these diseases. In this review, several enzyme-responsive nanomaterials such as polymer-based nanoparticles, liposomes, gold nanoparticles and quantum dots are introduced, and the modulation of their physicochemical properties by enzymatic activity emphasized. When known, toxicological issues related to the utilization nanomaterials are highlighted. Key examples of enzyme-responsive nanomaterials for drug delivery and diagnostics are presented, classified by the type of effector biomolecule, including hydrolases such as proteases, lipases and glycosidases, and oxidoreductases.
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