The importance of drug delivery to chemists, medicinal and otherwise, has increased since the advent of integrated drug discovery processes. Physicochemical and biological barriers, pathways for drug delivery, formulation, pharmacokinetic and pharmacodynamic issues, metabolism, and cell culture models used in studying drug delivery are just some of the topics that make drug delivery an exciting field for researchers.
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Selective delivery: Active drug targeting enhances the efficacy and specificity of systemic therapeutics. Aptamers, artificial nucleic acid ligands, represent powerful targeting tools that can act as cell-specific drug carriers. The advancements from the past decade have provided various approaches that open new gateways for drug administration in cancer therapy.
The heat is on: A thermoresponsive drug carrier with self-destruction property has been obtained by a facile one-pot preparation process. Enhanced drug release was achieved owing to the particle decomposition triggered by phase transformation of the copolymer upon temperature manipulation (see figure). The drug-loaded nanoparticles showed faster drug release in an acidic environment than in a neutral one.
Stimuli-responsive drug nanocarriers: Core–shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate (MIO@ACP) were prepared and investigated as drug-delivery systems. Hollow microspheres were prepared by HCl etching of solid microspheres, loaded with drugs, and coated with a protective layer of ACP by using disodium adenosine 5'-triphosphate (ATP) as the stabilizer. At pH 4.5 drug release was fast due to dissolution of the ACP shell.
Undercover double agent: Spindle-like polypyrrole hollow nanocapsules (PPy HNCs) can load and deliver anticancer drugs with high efficiencies; meanwhile, the polypyrrole (PPy) shells are an excellent agent for organic photothermal therapy (see figure; DOX=doxorubicin). Two cancer therapy methods were successfully combined to significantly improve the effect of tumor therapy in vitro and in vivo.
Moving tracks from maleimide: New site-selective protein modification reactions at cysteine have been developed. Unlike conventional maleimide conjugation, which results in a labile thioether succinimide, the new bioconjugation reactions result in stable conjugates and provide opportunities to develop a new generation of homogeneous, stable, and therapeutically useful conjugates.
On target: Carbon-monoxide-releasing molecules (CORMs) are promising agents for the treatment of several diseases. CORMs are particularly good for enabling CO delivery in a controlled manner without affecting oxygen transport by hemoglobin. Significant progress in the methods for CO detection in live cells and the understanding of the reactivity of CORMs in vivo provides insights into CO biology and the design of safer, and more selective and efficient CORMs for clinical use.
Intracellular express: An amphiphilic bicyclic peptide containing two monocyclic peptides was developed. The cellular uptake pathways were determined to be mainly clathrin- and lipid raft-caveolin-dependent endocytosis. The bicyclic peptide enhanced the delivery of a cell-impermeable negatively charged phosphopeptide and improved antiproliferative activity and retention of doxorubicin in human ovarian adenocarcinoma cells.
Smart vesicles: Electro-responsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) were loaded with the antiepileptic drug phenytoin sodium (PHT). The complex ANG-PHT-ERHNPs can easily transport the drug into the brain and a fast release could be achieved by the application of an electric field, leading to a reduction of the severity of the seizure onset.
Maximizing drug release from drug carriers is important to achieve better therapeutic efficiency. Using glutathione (GSH)-triggered drug-release systems as a case study, the effect of the nature of surface functional groups on mesoporous silica nanoparticles on drug-loading and drug-release capabilities was investigated.
Multifunctional nanoparticles: A new class of multifunctional zeolite-L particles has been realized for the simultaneous delivery of foreign DNA and organic molecules into living cells (see figure). Due to the remarkable cellular internalization and release kinetics, this system may open a way towards efficient nucleic acid transfection, drug delivery, and gene therapy applications.
On target: A lipidated cathepsin B (CtsB) inhibitor was incorporated into the envelope of a liposomal nanocarrier. The resulting CtsB-targeted drug delivery system, which can be loaded with diagnostic or therapeutic agents, was selectively internalized by tumor and stromal cells, thus validating CtsB targeting as a promising approach to cancer diagnosis and treatment.
MOF nanocarrier: A new GdIII-based porous metal–organic framework, Gd-pDBI, with an elongated rotatable linker (DBI=(1,4-bis(5-carboxy-1H-benzimidazole-2-yl)benzene) was synthesized. Gd-pDBI is biocompatible, water-stable, and acid/base-tolerant. Mechanical grinding yielded nanocrystals with excellent water dispersibility, and they feature the highest loading of the anticancer drug doxorubicin (DOX) and cancer-cell-specific drug release.
Disulfide-containing IgG-, Fc-, or albumin-based prodrugs that rely on FcRn-trafficking by endothelial cells for prolonged circulation in the body might be hampered by premature bio-reduction processes during FcRn-recycling events. A detailed bio-reduction analysis of redox-sensitive albumin conjugates in two FcRn-expressing cell lines has been performed. New insights are provided to improve the performance of these classes of therapeutics.
Fighting cancer: Quercetin surface-functionalized germanium nanoparticles (Qu-GeNPs) with enhanced antioxidant and anticancer activity were synthesized by a simple method (see scheme). In vitro drug release of Qu from Qu-GeNPs indicated that Qu could principally be distributed around tumor tissues, and Qu-GeNPs were internalized by MCF-7 cells.
Taking turns: Inclusion of covalent and copper-free click chemistry in layer-by-layer thin films during assembly generates sequential release behavior without modification of the protein itself. Increasingly thick barrier layers deposited on protein-containing layers delay the onset of protein release, which can be harnessed to generate well-defined sequential protein release with minimal overlap.
Autonomous drug-delivery system: The newly synthesized, pH-triggered, hybrid silica nanoparticles with molecular-recognition sites meet the needs for non-premature drug release (see figure) and allow to significantly decrease the amount of the administered drug camptothecin.
Better together: Two new 8-hydroxyquinoline-appended cyclodextrins are reported (see scheme) and their multifunctional properties are highlighted, including their CuII and ZnII binding abilities, and their capacity to act as antioxidants and antiaggregants.
Three in one: A theranostic nanoplatform based on a conjugated polyelectrolyte covalently linked to an anticancer drug (orange) through a linker (green) cleaved by reactive oxygen species (ROS) had functionalities for image, therapy, and on-demand drug release (see picture). An enhanced therapeutic effect was possible through combined photodynamic therapy and chemotherapy with ROS-triggered drug release upon illumination with a single light switch.
Combined cargo combats cancer: A selective release system was demonstrated with dual-cargo-loaded mesoporous silica nanoparticles (MSNs). When stimulated by different signals (UV or H+; see figure), this system could selectively release different kinds of cargoes in turn. In addition, this system has been used to provide a combination of chemotherapy and biotherapy for cancer treatment.
PCMs on the rise: As a result of their sharp melting points and large heats of fusion during phase transition, phase-change materials (PCMs) have already found commercial use in thermal management. The vast potential of this class of fascinating materials has recently been tapped in a diverse array of high-tech applications such as controlled release, information storage, sensing/detection, and barcoding.
Release on demand: The pH gradients between extra- and intracellular regions can be utilized for the controlled release of drugs and biological cargos from delivery systems. Biocompatible carrier systems with pH-cleavable units must fulfill many other criteria as well, for example, a long blood circulation time. This can be achieved by tailored micro- and nanocarriers based on macromolecular architectures or stable self-assembled systems.
Missing a piece? We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects and to increase drug-delivery efficiency. The unfinished puzzle in the picture shows the Aesculapian snake—the symbol of pharmacy and cure—to remind us that there is still a gap between potent chemotherapeutics and radiotherapy. We hope the emerging research area summarized in this Focus Review can function as the connecting pieces to solve the puzzle of an effective and comprehensive treatment.
Right on target! This concept article presents current research and developments on the application of polymeric micelles as nanocarriers for multidrug delivery and combination therapy. The advances of this concept focus on the targeted drug delivery for cancer, gene, and RNA therapies using systemic administration. Finally, the application of multidrug micelles combined with drug-releasing implants for local delivery based on titania nanotubes is summarized.
Bedknobs and broomsticks: This Focus Review discusses the current status in the development of synthetic procedures, recently explored substrates, innovative applications, and the accompanying challenges of surface-grafted macromolecular assemblies.
What's new under the sun? Hiding, protecting and shielding a photosensitiser in the cavity of a water-soluble arene-ruthenium metallacage (see figure) can provide a solution to eliminate skin photosensitivity, an important limitation to photodynamic treatments.
Fine print: The title technology is a continuous, roll-to-roll, high-resolution molding technology that allows the design and synthesis of precisely defined micro- and nanoparticles. This technology enables researchers to have unprecedented control over particle size, shape, chemical composition, cargo, modulus, and surface properties. Recent work involving the PRINT technology for application in the biomedical and material sciences is described.
The subunit approach: Despite their excellent track record, traditional vaccine approaches have failed for several high priority diseases. Subunit vaccines offer hope for new, safer, highly characterized vaccines. Herein we discuss key components for next-generation subunit vaccine development.
On target: Antibodies have emerged as promising vehicles for the targeted delivery of potent cytotoxic agents to sites of disease. This Review surveys how the use of smaller organic molecules can yield targeted constructs with improved properties and how DNA-encoded library technologies will facilitate the discovery of the necessary ligands (see scheme).
Helices, screws or twists transform rotational motion into translations in soft tissue or fluidic environments. The actuation occurs wirelessly through low-strength rotating magnetic fields. These swimming microrobots can be used for micro-object or microfluidic manipulation tasks or as transport platforms for targeted delivery in medical applications.