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Advanced Drug Delivery Reviews (v.60, #9)
Materials for advanced drug delivery in the 21st century: a focus area for Advanced Drug Delivery Reviews
by Hamidreza Ghandehari Executive Editor (pp. 956-956).
Design and development strategies of polymer materials for drug and gene delivery applications
by David Oupicky (pp. 957-957).
Efficient construction of therapeutics, bioconjugates, biomaterials and bioactive surfaces using azide–alkyne “click” chemistry by Jean-François Lutz; Zoya Zarafshani (pp. 958-970).
The concept of “click” chemistry, introduced by Sharpless and coworkers a couple of years ago, promotes the use of efficient, selective and versatile chemical reactions in synthetic chemistry. For instance, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) is regarded as a prime example of “click” chemistry. This reaction is regioselective, chemoselective and moreover can be performed in aqueous medium at room or physiological temperature. Thus, CuAAC became lately a very popular ligation tool in biological and medical sciences. Several hundred of articles exploring the synthetic possibilities of CuAAC in biosciences have been published within the last four years. The aim of the present review is to give an overall – non exhaustive – picture of this emerging field of research. The advantages and versatility of CuAAC in scientific disciplines as diverse as drug discovery, biochemistry, bioconjugates synthesis, drug-delivery, gene therapy, bioseparation or diagnostics are presented and discussed in detail.
Keywords: “Click” chemistry; Drug design; Combinatorial chemistry; Polymer–bioconjugates; Drug-delivery; Micelles; Nanoparticles; Nanomedicine; Diagnostics; Biosurfaces; Biochips; Hydrogels; Biopolymers
Combinatorial and rational approaches to polymer synthesis for medicine by Michael Goldberg; Kerry Mahon; Daniel Anderson (pp. 971-978).
High-throughput, combinatorial methods have revolutionized small molecule synthesis and drug discovery. By combining automation, miniaturization, and parallel synthesis techniques, large collections of new compounds have been synthesized and screened. It is becoming increasingly clear that these same approaches can also assist the discovery and development of novel biomaterials for medicine. This review examines combinatorial and rational polymer synthesis for medical applications, including stem cell engineering and nucleic acid drug delivery.
Keywords: Combinatorial; Polymer; Synthesis; Stem cells; Nucleic acid delivery; Rational design; Drug delivery
Multilayered polyelectrolyte assemblies as platforms for the delivery of DNA and other nucleic acid-based therapeutics by Christopher M. Jewell; David M. Lynn (pp. 979-999).
Materials that provide spatial and temporal control over the delivery of DNA and other nucleic acid-based agents from surfaces play important roles in the development of localized gene-based therapies. This review focuses on a relatively new approach to the immobilization and release of DNA from surfaces: methods based on the layer-by-layer assembly of thin multilayered films (or polyelectrolyte multilayers, PEMs). Layer-by-layer methods provide convenient, nanometer-scale control over the incorporation of DNA, RNA, and oligonucleotide constructs into thin polyelectrolyte films. Provided that these assemblies can be designed in ways that permit controlled film disassembly under physiological conditions, this approach can contribute new methods for spatial and/or temporal control over the delivery of nucleic acid-based therapeutics in vitro and in vivo. We describe applications of layer-by-layer assembly to the fabrication of DNA-containing films that can be used to provide control over the release of plasmid DNA from the surfaces of macroscopic objects and promote surface-mediated cell transfection. We also highlight the application of these methods to the coating of colloidal substrates and the fabrication of hollow micrometer-scale capsules that can be used to encapsulate and control the release or delivery of DNA and oligonucleotides. Current challenges, gaps in knowledge, and new opportunities for the development of these methods in the general area of gene delivery are discussed.
Keywords: Gene delivery; Polyelectrolyte; Multilayered films; Layer-by-layer; DNA; Transfection; Capsules
Cyclodextrin-based supramolecular architectures: Syntheses, structures, and applications for drug and gene delivery by Jun Li; Xian Jun Loh (pp. 1000-1017).
The supramolecular structures formed between cyclodextrins (CDs) and polymers have inspired interesting developments of novel supramolecular biomaterials. This review will update the recent progress in studies on supramolecular structures based on CDs and block copolymers, followed by the design and synthesis of CD-based supramolecular hydrogels and biodegradable polyrotaxanes for potential controlled drug delivery, and CD-containing cationic polymers and cationic polyrotaxanes for gene delivery. Supramolecular hydrogels based on the self-assembly of the inclusion complexes between CDs with biodegradable block copolymers could be used as promising injectable drug delivery systems for sustained controlled release of macromolecular drugs. Biodegradable polyrotaxanes with drug-conjugated CDs threaded on a polymer chain with degradable end-caps could be interesting supramolecular prodrugs for controlled and targeting delivery of drugs. CD-containing cationic polymers as gene carriers showed reduced cytotoxicity than non-CD-containing polymer counterparts. More importantly, the polyplexes of CD-containing cationic polymers with DNA could be pegylated through a supramolecular process using inclusion complexation between the CD moieties and a modified PEO. Finally, new cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationic cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector. The development of the supramolecular biomaterials through inclusion complexation has opened up a new approach for designing novel drug and gene delivery systems, which may have many advantages over the systems based on the conventional polymeric materials.
Keywords: Cyclodextrin; Polymers; Supramolecular structures; Inclusion complex; Polypseudorotaxane; Polyrotaxane; Hydrogels; Cationic polymers; Drug delivery; Gene delivery
Advances in the synthesis of amphiphilic block copolymers via RAFT polymerization: Stimuli-responsive drug and gene delivery by Adam W. York; Stacey E. Kirkland; Charles L. McCormick (pp. 1018-1036).
Controlled/‘living’ radical polymerization methods, including the versatile reversible addition–fragmentation chain transfer (RAFT) polymerization process, are rapidly moving to the forefront in construction of drug and gene delivery vehicles. The RAFT technique allows an unprecedented latitude in the synthesis of water soluble or amphiphilic architectures with precise dimensions and appropriate functionality for attachment and targeted delivery of diagnostic and therapeutic agents. This review focuses on the chemistry of the RAFT process and its potential for preparing well-defined block copolymers and conjugates capable of stimuli-responsive assembly and release of bioactive agents in the physiological environment. Recent examples of block copolymers with designed structures and segmental compositions responsive to changes in pH or temperature are reviewed and hurdles facing further development of these novel systems are discussed.
Keywords: Water soluble polymers; Controlled release; Targeted delivery; Bioconjugation; Interpolyelectrolyte complexes; Cross-linked micelles; Stimuli-responsive polymers
Therapeutic and diagnostic applications of dendrimers for cancer treatment by Jesse B. Wolinsky; Mark W. Grinstaff (pp. 1037-1055).
Dendrimers are prepared with a level of control not attainable with most linear polymers, leading to nearly monodisperse, globular macromolecules with a large number of peripheral groups. As a consequence, dendrimers are an ideal delivery vehicle candidate for explicit study of the effects of polymer size, charge, composition, and architecture on biologically relevant properties such as lipid bilayer interactions, cytotoxicity, internalization, blood plasma retention time, biodistribution, and tumor uptake. Over the last several years, substantial progress has been made towards the use of dendrimers for therapeutic and diagnostic purposes for the treatment of cancer, including advances in the delivery of anti-neoplastic and contrast agents, neutron capture therapy, photodynamic therapy, and photothermal therapy. The focus of this review is on dendrimer developments from the last four years for oncological applications, with emphasis on distinct architectures and the biological responses these structures elicit.
Keywords: Dendrimer; Local Therapy; Nanoparticle; Cancer Treatment; Drug-conjugates; Drug Delivery
Recent advances in the synthesis of aliphatic polyesters by ring-opening polymerization by Christine Jérôme; Philippe Lecomte (pp. 1056-1076).
Advanced drug delivery systems rely on the availability of biocompatible materials. Moreover, biodegradability is highly desirable in the design of those systems. Consequently, aliphatic polyesters appear as a class of promising materials since they combine both properties. Nevertheless, their use in practical biomedical systems relies on clinical approval which not only depends on the material itself but also on its reproducible synthesis with the absence of residual toxics. The first sections of this review aim at reporting on the evolution of the initiators/catalytic systems and of the synthesis conditions (particularly the use of supercritical CO2 as polymerization medium) in order to produce aliphatic polyesters with controlled macromolecular parameters by still “greener” ways. In addition, the further development of delivery systems also depends on the synthesis of materials exhibiting novel properties, such as amphiphilicity or pH-sensitivity that are emerging from the active research in macromolecular engineering. Functionalizing aliphatic polyesters is quite tedious due to their sensitivity towards hydrolytic degradation. The last section of this review is discussing several strategies to obtain functional (co)polyesters of various architectures providing them with novel properties.
Keywords: Aliphatic polyesters; Ring-opening polymerization; Enzymatic polymerization; Supercritical carbon dioxide
Recent developments in enzyme-catalyzed ring-opening polymerization by Ann-Christine Albertsson; Rajiv K. Srivastava (pp. 1077-1093).
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 catalysts. 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 the 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.
Keywords: Lipase; Lactone; Lactide; Molecular weight; Catalysis; Aliphatic polyester; Aliphatic polycarbonates