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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Lanthanide oxide nanostructures (Sm2O3 and Gd2O3) with various morphologies (nanoflakes, nanowires, ultrathin nanosheets) were synthesized by a facile wet chemistry method. As a proof-of-concept, the Sm2O3 and Gd2O3 ultrathin nanosheets demonstrate promising pH-controlled anticancer drug-delivery behavior.
Get smart: A smart targeting gene carrier for cancer-specific delivery has been successfully prepared by a “multilayer bricks-and-mortar” strategy. Carriers produced by two different self-assembly schemes were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the most suitable (Method A) material has lower cytotoxicity than 25 kDa bPEI and that transfection efficiency is maintained.
Attractive interactions can arise between a fluorocarbon gas and a C2F5-labeled compound (red triangle with green tail) across a phospholipid monolayer, allowing recruitment and immobilization of the fluorinated compound in the phospholipid layer. This new phenomenon allowed preparation of microbubbles loaded with a C2F5-labeled hypoxia biomarker.
Yolk-shell porous microspheres: Yolk-shell porous microspheres of calcium phosphate were prepared by using calcium L-lactate pentahydrate and adenosine 5'-triphosphate disodium salt by the microwave-assisted hydrothermal method (see figure). The as-prepared yolk-shell porous microspheres have a high protein/drug loading capacity, sustained release behavior, favorable pH-responsive release and high biocompatibility. Thus, they are promising for applications in various biomedical fields such as protein/drug delivery.
Stealth nanocarriers: The blood plasma interactions and targeting properties of PEGylated and mannose-functionalized hydroxyethyl starch (HES) nanocarriers were investigated. They exhibit colloidal stability in human plasma, low protein adsorption, a distinct protein pattern, and highly specific cellular uptake into dendritic cells both before and after contact with human plasma.
Mussel-inspired protein nanoparticles that are capable of pH-responsive drug release were obtained by exploiting the pH-dependent changes in the stoichiometry of iron(III)–DOPA complexes. Such doxorubicin-loaded polymeric nanoparticles were synthesized through a co-electrospraying process and shown to release doxorubicin at acidic pH values. DOPA=3,4-dihydroxyphenylalanine.
Manno, manno! Fluorescent glycoconjugates composed of a peptide epoxysuccinate coupled via a BODIPY dye to oligomannosides (see figure) show mannose-receptor-dependent uptake and ensuing cathepsin inhibition in live dendritic cells. The size of the mannose oligosaccharides proved to influence the amount of inhibition.
Drug release quantified: We have developed a new modular approach for the preparation of theranostic prodrugs with a turn-ON near-infrared (NIR) fluorescence mode of action. The prodrugs release their chemotherapeutic cargo and an active cyanine fluorophore upon reaction with a specific analyte. The release of the drug can be monitored through the produced NIR fluorescence.
Fine-tuning stability: Bis(benzoyloxybenzyl) groups were used to mask two of the negative charges of nucleoside diphosphates to form DiPPro compounds. Modification by different substituents in the 4-positions had a strong impact on the chemical and enzymatic stability. With strong acceptor substituents, the NDPs were released almost exclusively in PBS or in cell extracts.
Linked up: The human Y1 receptor preferring peptide [F7,P34]NPY is coupled to methotrexate through different cleavable linker structures for prospective breast cancer therapy. The toxicity of these novel peptide–drug conjugates is clearly dependent on the linkage type and a new linker is identified.
Get a response! pH-Responsive drug-delivery systems have promising applications because they are “smart” or “intelligent” in overcoming the shortcomings of conventional drug formulations and are able to deliver drugs in a controlled manner at specific sites and times, which results in high therapeutic efficacy. Recent progress obtained for pH-responsive drug-delivery systems and future perspectives is presented.
Nanotherapeutics are designed and constructed from mesoporous silica nanoparticles for the targeted treatment of cancer based on characteristics of tumor tissues. The picture shows drug delivery triggered by the acidic extracellular environment of cancer, endocytosis of the drug carrier, and intracellular release of cargo drugs.
Targeted & Specific: The applications of nucleic acid aptamers in cancer are reviewed. Single-stranded (ss) oligonucleotide (DNA or RNA)-based aptamers conjugated with drugs and nanomaterials are covered in detail, highlighting their therapeutic potential while acknowledging the challenges that remain to be overcome.
Bringing life from cell death: Stimuli-responsive polymeric nanoparticles can respond to the microenvironment of a particular disease and its cells. Internal triggers as well as external devices permit temporally and spatially controlled drug delivery. The development of well-defined nanomedicines is critical for their behavior in vivo.
On the way to nanomedicine: Considerable advances in the development of nanoparticles for cancer therapy have been made in recent years. Nanoparticle-based drug-delivery systems offer advantages with regard to multidrug resistance, systemic delivery, and clearance, and enable for example specific tumor targeting and controlled release of therapeutic agents.
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.
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.
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.