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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Research into the delivery of large polar molecules and their detection in the mitochondrial matrix is held back by the lack of a robust and quantitative measure of import. Here, we demonstrate a mitochondrial matrix-specific click reaction, forming a diagnostic product that can be quantified by mass spectrometry.
Kurt Hoogewijs, Andrew M. James, Robin A. J. Smith, Michael J. Gait, Michael P. Murphy, Robert N. Lightowlers
ChemBioChem, May 25, 2016, DOI: 10.1002/cbic.201600188. Read article
Special delivery: The studied surfactants form stable complexes with DNA and RNA oligonucleotides, causing condensation of the nucleic acids while maintaining their native conformation. The surfactants form a micellar phase in solution; however, in the IMI_Gly_n2_C12/DNA system, a hexagonal phase is also formed and the 2,8-dioxanonane surfactant-based systems have a tendency to form a cubic phase and more complex 3D structures, both with RNA and DNA.
Zuzanna Pietralik, Andrzej Skrzypczak, Maciej Kozak
ChemPhysChem, May 23, 2016, DOI: 10.1002/cphc.201600175. Read article
Two Zn-based porous metal-organic frameworks, ZJU-64 and ZJU-64-CH3 sharing the same crystal structure, have been synthesized from zinc ions, biomolecular linker adenine and carboxylates-based ligands, resulting in three-dimensional frameworks with one-dimensional channels (around 1.6 nm × 1.9 nm). The material ZJU-64 and ZJU-64-CH3 exhibit low-toxic natures by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and microscopy photos indicating their potential applications for human health care. The anticancer drug methotrexate (MTX) is successfully loaded into MOFs via a simple impregnation method and the drug payloads reach to about 13.45 wt% and 10.63 wt% for ZJU-64 and ZJU-64-CH3, respectively. Sustainable drug release behaviors of MTX from MTX-loaded ZJU-64 and MTX-loaded ZJU-64-CH3 for several days are detected. The temperature-responsive deliveries of ZJU-64 and ZJU-64-CH3 reveal hyperthermia can control the drug release and open up a new treatment which combines drug therapy and thermal therapy to kill more cancer cells with less side effects, revealing the practical values of ZJU-64 and ZJU-64-CH3 as "smart" drug carriers with more therapeutic efficacy.
Wenxin Lin, Quan Hu, Jiancan Yu, Ke Jiang, Yanyu Yang, Shengchang Xiang, Yuanjing Cui, Yu Yang, Zhiyu Wang, Guodong Qian
ChemPlusChem, May 19, 2016, DOI: 10.1002/cplu.201600142. Read article
Metal–organic gels are capable of storing anticancer drugs within the pores, and then releasing them under acidic pH or in the presence of glutathione. In vitro experiments show a low toxicity of metal–organic gels and confirm the triggered drug release.
Si Yu Tan, Chung Yen Ang, Asif Mahmood, Qiuyu Qu, Peizhou Li, Ruqiang Zou, Yanli Zhao
ChemNanoMat, May 19, 2016, DOI: 10.1002/cnma.201600078. Read article
Biomimetically coated core–shell SiO2@TiO2 nanoparticles with enhanced photocatalytic activity are able to shed their surface erythrocyte membrane coatings by UV-light–triggered degradation of the latter. This approach demonstrates the potential of using biomimetic cell-membrane–coated nanocarriers for controlled drug delivery.
Lang Rao, Qian-Fang Meng, Qinqin Huang, Pei Liu, Lin-Lin Bu, Kiran Kumar Kondamareddy, Shi-Shang Guo, Wei Liu, Xing-Zhong Zhao
Adv. Healthcare Mater., May 18, 2016, DOI: 10.1002/adhm.201600303. Read article
Improving therapeutic efficiency and reducing the side-effects of chemotherapy in patients are attractive issues but still hold a critical challenge. In this work, a novel SiO2-based nanocarrier coated with polylactic acid (PLA) and folate (FA) has been fabricated to destruct the tumor in vivo. FA promotes the targeting intracellular delivery of drug molecules against folate receptor (FR) overexpressed cancer cells, improving the therapy efficiency. PLA layer avoids the premature leakage of drug until the PLA is degraded on the response to low pH and enzyme to realize sustained and on-demand drug release, avoiding the undesired side-effects. Escape of the drug molecules then triggers the SiO2 carrier decomposition, improving its elimination from the biosystem. The strategy of combining the engineering flexibility of inorganic nanocarriers with the stimuli-responsive biodegradability of organic molecules will open new directions in on-demand and sustained drug release for chemotherapy.
Zhifang Ma, Xiaolei Li, Xiaodan Jia, Jing Bai, Xiue Jiang
ChemPlusChem, May 11, 2016, DOI: 10.1002/cplu.201600100. Read article
Give me some space! We report a systematic investigation of the interactions between PEG and DNA aptamer strands with spacer molecules of different sizes and compositions on the surface of liposomal doxorubicin. A spacer of appropriate length was critical to overcome the shielding of surrounding PEG molecules in order to achieve the best targeting effect.
Hang Xing, Ji Li, Weidong Xu, Kevin Hwang, Peiwen Wu, Qian Yin, Zhensheng Li, Jianjun Cheng, Yi Lu
ChemBioChem, May 11, 2016, DOI: 10.1002/cbic.201600092. Read article
The latest advances in the utilization of versatile peptides for surface functionalization of mesoporous silica nanoparticles (MSNs) to achieve site-specific targeting, fluorescence imaging, and intracellular diagnosis, especially controlled release of drugs or genes for tumor treatment are highlighted.
Jing-Jing Hu, Dong Xiao, Xian-Zheng Zhang
Small, May 06, 2016, DOI: 10.1002/smll.201600325. Read article
Azide-bearing poly(ethylene glycol)-polycarbonate block copolymer (mPEG-b-P(DTC-ADTC)) self-assembles to form micelles in water. The micelle cores are crosslinked with a disulfide-containing dialkynyl compound (SS-Linker) via the azide-alkyne click reaction to enhance the stability of the micelles and endow the micelles with redox-responsive ability.
Xiaojin Zhang, Hui Dong, Shuangli Fu, Zhenlin Zhong, Renxi Zhuo
Macromol. Rapid Commun., May 06, 2016, DOI: 10.1002/marc.201600049. Read article
Molecular polymer brushes present an emerging class of polymer nanostructures with the potential to address persevering problems in nanomedicine. Recent improvements in the synthesis of these polymeric architectures allowed the tailoring of sophisticated nanomaterials for applications in drug and gene delivery, as well as the design of new imaging probes and prototype nanomaterials.
Macromol. Chem. Phys., May 06, 2016, DOI: 10.1002/macp.201600086. Read article
Polysaccharides are ideal candidates for drug delivery and biomedical applications as they are easily obtained from natural sources. Furthermore, they can be subjected to a wide range of chemical and enzymatic reactions, have biocompatible and biodegradable properties and are inherently low in immunogenicity. Polysaccharides are potentially the materials of choice for the development of "smart" delivery systems which are capable of releasing, at the appropriate time and site of action, the encapsulated drugs. In this review, we will look at various aspects of crosslinking a polysaccharide either for a single polysaccharide or mixtures and also a hybrid natural/synthetic combination. We also focus on strategies of using these biodegradable polymers for controlled drug delivery. We further look at polysaccharide drug conjugates, the encapsulation of drug in hydrogels and aerogels and the formation of polysaccharide drug loaded nanoparticles by self-assembly.
Pushpa Janarthanan, Anand Kumar Veeramachineni, Cally Owh, Xian Jun Loh
ChemPlusChem, May 04, 2016, DOI: 10.1002/cplu.201600112. Read article
The facile synthesis of low dispersity photocleavable polymers are demonstrated for the first time using a novel photopolymerization approach. Under a visible light stimulus (530–655 nm), poly(o-nitrobenzyl methacrylate) polymers are readily synthesized using a metal-based or organic photoredox catalyst with good polymerization control.
Ali Bagheri, Jonathan Yeow, Hamidreza Arandiyan, Jiangtao Xu, Cyrille Boyer, May Lim
Macromol. Rapid Commun., April 28, 2016, DOI: 10.1002/marc.201600127. Read article
Inhibiting the crowd: Cyclodextrins are assayed as antiaggregant agents, and a number of data show their capability to inhibit the aggregation of proteins. This review aims to be a stimulus to the design of new cyclodextrin derivatives with antiaggregant activities.
Valentina Oliveri, Graziella Vecchio
Chem. Asian J., April 28, 2016, DOI: 10.1002/asia.201600259. Read article
In this work, a strategy to explore nanoscale metal-organic frameworks (nano-MOFs) as templates for the layer-by-layer (LbL) assembly of polyelectrolytes was developed. As small-molecule drugs or imaging agents cannot be efficiently encapsulated by polyelectrolyte nanocapsules, two promising and biocompatible polymers (i.e., comb-shaped polyethylene glycol (PEG) and hyperbranched polyglycerol-based PEG) were exploited for the conjugation of model drugs and imaging agents, which were then encapsulated into the nano-MOF-templated nanocapsules. Moreover, we systemically explored the release kinetics of the encapsulated conjugates, and examined how the encapsulation and/or release processes can be controlled by varying the composition and architectures of the polymers. We envision that our nano-MOFs-templated nanocapsules, through combining with small molecule-polymer conjugates, would represent a new type of delivery systems which might open new opportunities for biomedicine applications.
Chuanliu Wu, Shuo Liu, Jianbin Chen, Xiaojia Bao, Tao Li, Yunyang Ling, Chunxiang Li, Yibing Zhao
Chem. Asian J., April 28, 2016, DOI: 10.1002/asia.201600250. Read article
Critical β-cell mass: Pancreas-specific delivery of a β-cell proliferation agent, aminopyrazine (AP), was achieved by attaching it onto (+)-dihydrotetrabenazine (DTBZ) through a non-cleavable linker. This is the first demonstration of enhanced delivery of β-cell-proliferating molecules to the pancreas by leveraging the intrinsic tissue specificity of a β-cell imaging agent.
Xueshi Hao, Qihui Jin, Porino Va, Chun Li, Weijun Shen, Bryan Laffitte, Tom Y.-H. Wu
ChemMedChem, April 20, 2016, DOI: 10.1002/cmdc.201600116. Read article
Unlocking molecule release: A dual-responsive lyotropic liquid crystal system for the controlled release of molecules is reported.
Dong Wang, Yueying Cao, Meiwen Cao, Yawei Sun, Jiqian Wang, Jingcheng Hao
ChemPhysChem, April 08, 2016, DOI: 10.1002/cphc.201600066. Read article
This account describes our recent progress in the development of pillararene-based stimuli-responsive supramolecular nanostructures constructed by reversible noncovalent host–guest interactions with the aim of creating smart and functional supramolecular drug delivery systems for controllable anticancer drug delivery. The potential applications and fundamental questions of these supramolecular drug carriers in cancer treatment are also discussed.
Xuan Wu, Lei Gao, Xiao-Yu Hu, Leyong Wang
The Chemical Record, April 07, 2016, DOI: 10.1002/tcr.201500265. Read article
Micelles formed by weakly amphiphilic poly(2-oxazoline) triblock copolymers have a very high loading capacity for the cancer drug Paclitaxel. The aggregation behavior of the micelles is investigated in dependence on Paclitaxel concentration using small-angle neutron scattering and is compared to the aggregation of strongly amphiphilic poly(2-oxazoline) triblock copolymers.
Sebastian Jaksch, Anita Schulz, Zhenyu Di, Robert Luxenhofer, Rainer Jordan, Christine M. Papadakis
Macromol. Chem. Phys., April 04, 2016, DOI: 10.1002/macp.201500465. Read article
Express delivery: A novel decorated liposome (L) was developed for selective artemisinin (ART) delivery and activation in cancer tissues, given their overexpression of transferrin (Tf) receptors (PEG: polyethylene glycol). Liposomes were characterized for size, drug-entrapment efficiency, transferrin coupling moieties, and stability. Cell uptake and cytotoxicity were tested in the HCT-8 cell line. We found enhanced selectivity and improved cytotoxicity, resulting in concomitant synergism.
Isabella Leto, Marcella Coronnello, Chiara Righeschi, Maria Camilla Bergonzi, Enrico Mini, Anna Rita Bilia
ChemMedChem, March 21, 2016, DOI: 10.1002/cmdc.201500586. Read article
Mesoporous silica nanocarriers with pH-switchable antifouling zwitterionic surface, enzyme responsive drug release properties and blue fluorescence are reported. Prolonged circulation in the blood system with zero premature release as well as efficient cellular uptake and intracellular drug release in tumor tissue are achieved.
Zhongning Liu, Xin Chen, Xiaojin Zhang, John Justin Gooding, Yongsheng Zhou
Adv. Healthcare Mater., March 14, 2016, DOI: 10.1002/adhm.201600002. Read article
A unique formulation of choline, geranate, and geranic acid eutectic solvent (CAGE) holds promise as a transformative platform for the prevention and treatment of microbial infections.
Michael Zakrewsky, Amrita Banerjee, Sanjana Apte, Theresa L. Kern, Mattie R. Jones, Rico E. Del Sesto, Andrew T. Koppisch, David T. Fox, Samir Mitragotri
Adv. Healthcare Mater., March 09, 2016, DOI: 10.1002/adhm.201600086. Read article
Coming together: Human serum albumin nanoparticles (NPs) were prepared through two different cross-linking methods. The NPs were optimized in terms of size, homogeneity, and stability in order to generate carriers able to cross the blood–brain barrier. Their capacity to do so was evaluated after systemic administration in healthy rats. The distribution, cellular uptake, and fate were investigated in vivo. Toxicity was estimated by behavioral tests.
Maria C. Bergonzi, Clizia Guccione, Cristina Grossi, Vieri Piazzini, Andrea Torracchi, Ilaria Luccarini, Fiorella Casamenti, Anna R. Bilia
ChemMedChem, March 07, 2016, DOI: 10.1002/cmdc.201600080. Read article
Self-assembled metallocages of the type Pd2L4 are promising delivery vehicles for the anticancer drug cisplatin. Drug encapsulation was proven by different methods, and the biological properties were investigated in cancer cells also with the aid of fluorescence microscopy. The host–guest systems possess improved toxic effects in ovarian cancer cells compared to cisplatin while having limited toxicity in liver tissues (see scheme).
Andrea Schmidt, Viviana Molano, Manuela Hollering, Alexander Pöthig, Angela Casini, Fritz E. Kühn
Chem. Eur. J., January 12, 2016, DOI: 10.1002/chem.201504930. Read article.
Messenger of death: A new drug-delivery system based in mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid (poly(I:C)) for targeting breast carcinoma cells is reported (see figure).
Amelia Ultimo, Cristina Giménez, Pavel Bartovsky, Elena Aznar, Félix Sancenón, M. Dolores Marcos, Pedro Amorós, Ana R. Bernardo, Ramón Martínez-Máñez, Ana M. Jiménez-Lara, José R. Murguía
Chem. Eur. J., January 7, 2016, DOI: 10.1002/chem.201504629. Read article.
It’s all in the delivery: The inhibitor shown here is a nanomolar, dendron-based divalent sulfonamide that can bind gelatinase (MMP-9), the most important MMP on the ocular surface, and the transmembrane human carbonic anhydrase XII, present in eyes and considered an antiglaucoma target. In an animal model of a dry eye, no evidence of corneal desiccation was observed in eyes treated with our inhibitor.
B. Richichi, V. Baldoneschi, S. Burgalassi, M. Fragai, D. Vullo, A. Akdemir, E. Dragoni, A. Louka, M. Mamusa, D. Monti, D. Berti, E. Novellino, G. De Rosa, C. T. Supuran, C. Nativi
Chem. Eur. J., December 22, 2015, DOI: 10.1002/chem.201504355. Read article.
Through the barricades: Controlled multi-functionalization of nanoparticles with a cytotoxic drug, a glycan ligand for the cell surface receptor CD22, and an imaging moiety led to a remarkable 60-fold enhancement in cytotoxicity of CD22 (+) lymphoma cells compared to non-targeted nanoparticles.
Manish S. Hudlikar, Xiuru Li, Ivan A. Gagarinov, Nagesh Kolishetti, Margreet A. Wolfert, Geert-Jan Boons
Chem. Eur. J., December 18, 2015, DOI: 10.1002/chem.201503999. Read article.
Coordinated functions: A series of MnII-based coordination polymers were derived from different non-steroidal anti-inflammatory drugs (NSAIDs), which showed excellent cell imaging, in vitro anti-inflammatory and drug delivery properties (see figure).
Mithun Paul, Parthasarathi Dastidar
Chem. Eur. J., December 11, 2015, DOI: 10.1002/chem.201503706. Read article.