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Drug Delivery

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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A Strain-Regulated, Refillable Elastic Patch for Controlled Release

A Strain‐Regulated, Refillable Elastic Patch for Controlled Release

A refillable, elastic drug release patch that is responsive to external strain is suggested. The response is predicted by finite element method modeling. The release behavior is finely controlled by the attached microchannel. Systematic designs for on/off release and various controlled releases are realized.

[Full Paper]
Bongsoo Kim, SangHyuk Yoo, Yong-Jin Kim, Jaeyoon Park, Byunghoon Kang, Seungjoo Ham, Sun-Woong Kang, Keonwook Kang, Unyong Jeong
Adv. Mater. Interfaces, February 08, 2016, DOI: 10.1002/admi.201500803. Read article

Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins

Drug delivery: A novel polymeric nanoparticle platform that is capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside was developed by self-assembly. The surface coating with transferrin drastically changed the cellular behavior of the nanoparticles and enhanced the transepithelial transport by transcytosis.

[Communication]
Xi Zhu, Jun Wu, Wei Shan, Wei Tao, Lili Zhao, Jong-Min Lim, Mathew D'Ortenzio, Rohit Karnik, Yuan Huang, Jinjun Shi, Omid C. Farokhzad
Angew. Chem. Int. Ed., February 05, 2016, DOI: 10.1002/anie.201509183. Read article

A Telomerase-specific Doxorubicin-releasing Molecular Beacon for Cancer Theranostics

A Telomerase‐specific Doxorubicin‐releasing Molecular Beacon for Cancer Theranostics

Telomerase beacons: A molecular-beacon-based drug delivery system was designed for both detection of telomerase activity in living cells and telomerase-triggered drug release. This molecular beacon could specifically distinguish tumor cells and normal cells on the basis of telomerase activity, release doxorubicin, and avoid toxicity in healthy organs.

[Communication]
Yi Ma, Zhaohui Wang, Min Zhang, Zhihao Han, Dan Chen, Qiuyun Zhu, Weidong Gao, Zhiyu Qian, Yueqing Gu
Angew. Chem. Int. Ed., February 05, 2016, DOI: 10.1002/anie.201509182. Read article

Smart Ferrofluid with Quick Gel Transformation in Tumors for MRI-Guided Local Magnetic Thermochemotherapy

Smart Ferrofluid with Quick Gel Transformation in Tumors for MRI‐Guided Local Magnetic Thermochemotherapy

A biocompatible smart ferrofluid that transforms into a gel immediately after injection into tumors has the potential to facilitate a combination of magnetic hyperthermia and chemotherapy, under the guidance of magnetic resonance imaging. Magnetic thermochemotherapy using the smart ferrofluid shows significantly greater therapeutic efficacy than chemotherapy alone or magnetic hyperthermia alone.

[Full Paper]
Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo
Adv. Funct. Mater., February 05, 2016, DOI: 10.1002/adfm.201504215. Read article

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image‐Guided Approaches

Magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. An overview of recent advances in development and application of MNPs for drug delivery is provided with a focus on strategies for targeted and image-guided drug delivery. MNP carrier fabrication, delivery mechanisms, active targeting approaches, and image-guided drug deliveries are reviewed. Concluding remarks and future perspectives for MNP drug delivery are presented.

[Feature Article]
Jing Huang, Yuancheng Li, Anamaria Orza, Qiong Lu, Peng Guo, Liya Wang, Lily Yang, Hui Mao
Adv. Funct. Mater., February 05, 2016, DOI: 10.1002/adfm.201504185. Read article

Externally Controlled Nanomachines on Mesoporous Silica Nanoparticles for Biomedical Applications

Many machines (including nanomachines) consist of a solid support with moving parts that can undergo large amplitude motion to carry out specific tasks. In this review, we will describe nanomachines that are supported on mesoporous silica nanoparticles that are typically 50-100 nanometers in diameter and have an array of open, readily accessible pores with an average width of a few nanometers. For triggering a large amplitude motion of the moving parts, we will focus primarily on external stimuli such as heat or light. As for the specific task the machines are carrying out, this review will focus on the controlled release of pharmaceutically active agents in biomedical applications. We will discuss examples of how nanomachines can be used for remotely controlled cargo release and how existing machines that were originally designed to respond to internal physiological stimuli could be reconfigured to respond to external stimuli instead.

[Minireview]
Bastian Ruehle, Philippe Saint-Cricq, Jeffrey I. Zink
ChemPhysChem, February 03, 2016, DOI: 10.1002/cphc.201501167. Read article

Biomaterial-Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

Advances in cell and drug delivery platforms comprise the use of a biomaterial depot which can be delivered in a minimally invasive fashion. These materials can be delivered site specifically and can permit the controlled release of biotherapeutics in a multimodal fashion.

[Review]
Hugh S. O'Neill, Laura B. Gallagher, Janice O'Sullivan, William Whyte, Clive Curley, Eimear Dolan, Aamir Hameed, Joanne O'Dwyer, Christina Payne, Daniel O'Reilly, Eduardo Ruiz-Hernandez, Ellen T. Roche, Fergal J O'Brien, Sally Ann Cryan, Helena Kelly, Bruce Murphy, Garry P. Duffy
Adv. Mater., February 03, 2016, DOI: 10.1002/adma.201505349. Read article

DNA Origami: Folded DNA-Nanodevices That Can Direct and Interpret Cell Behavior

DNA Origami: Folded DNA‐Nanodevices That Can Direct and Interpret Cell Behavior

DNA origami can exploit the natural spatial addressability of DNA to create precise nanoscale shapes that can carry cargoes. This flexible design potential makes it an excellent candidate to direct or probe cell behavior. Here, the history and design principles of DNA origami and the recent advances and future challenges for these structures in biomedical applications including drug delivery are described.

[Progress Report]
Cathal J. Kearney, Christopher R. Lucas, Fergal J. O'Brien, Carlos E. Castro
Adv. Mater., February 03, 2016, DOI: 10.1002/adma.201504733. Read article

An Intrinsically Disordered Peptide Facilitates Non-Endosomal Cell Entry

An Intrinsically Disordered Peptide Facilitates Non‐Endosomal Cell Entry

Disorder imparts order: CLIP6, an intrinsically disordered peptide, mediates cellular entry through non-endosomal physical translocation across the membrane. This activity, defined by its unstructured state, facilitates the delivery of membrane-impermeable cargo to the interior of cells.

[Communication]
Scott H. Medina, Stephen E. Miller, Allison I. Keim, Alexander P. Gorka, Martin J. Schnermann, Joel P. Schneider
Angew. Chem. Int. Ed., February 02, 2016, DOI: 10.1002/anie.201510518. Read article

Protocells: Modular Mesoporous Silica Nanoparticle-Supported Lipid Bilayers for Drug Delivery

Protocells: Modular Mesoporous Silica Nanoparticle‐Supported Lipid Bilayers for Drug Delivery

Targeted drug delivery poses challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. This review describes the features and synthesis of the individual components, their assembly into protocells, the performance of the protocell in vitro and in vivo, and goals for its future development.

[Review]
Kimberly S. Butler, Paul N. Durfee, Christophe Theron, Carlee E. Ashley, Eric C. Carnes, C. Jeffrey Brinker
Small, January 18, 2016, DOI: 10.1002/smll.201502119. Read article

Self-Assembled Oleic Acid Nanoparticle Mediated Inhibition of Mitogen-Activated Protein Kinase Signaling in Combination with DNA Damage in Cancer Cells

Self‐Assembled Oleic Acid Nanoparticle Mediated Inhibition of Mitogen‐Activated Protein Kinase Signaling in Combination with DNA Damage in Cancer Cells

Double punch: Self-assembled oleic acid nanoparticles were engineered to simultaneously target mitogen-activated protein kinase (MAPK) signaling and damage DNA in cancer cells for improved therapeutic efficacy.

[Full Paper]
Sandeep Palvai, Piyush More, Nikunj Mapara, Jyothi Nagraj, Rajdeep Chowdhury, Sudipta Basu
ChemNanoMat, January 15, 2016, DOI: 10.1002/cnma.201500195. Read article

Hybrid Hierarchical Porous Silica Templated in Nanoemulsions for Drug Release

Hybrid Hierarchical Porous Silica Templated in Nanoemulsions for Drug Release

A nanocarrier for loading and releasing ketoprofen combines nanoemulsions with mesostructured silica. The release of the drug is pH responsive. By contrast, for the impregnation of ketoprofen in the bare macro-/mesoporous silica, a micelle-assisted release is observed. The modeling of the release profiles with the Korsmeyer–Peppas equation evidences a pseudo-Fickian release mechanism.

[Full Paper]
Philippe Riachy, Ferran Roig, Maria-José García-Celma, Marie-José Stébé, Andrea Pasc, Jordi Esquena, Conxita Solans, Jean Luc Blin
Eur. J. Inorg. Chem., January 12, 2016, DOI: 10.1002/ejic.201501127. Read article.

Evaluation of New Palladium Cages as Potential Delivery Systems for the Anticancer Drug Cisplatin

Evaluation of New Palladium Cages as Potential Delivery Systems for the Anticancer Drug Cisplatin

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).

[Communication]
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.

A smart approach for in situ one step encapsulation and controlled delivery of chemotherapeutic drug using metal organic framework-drug composite in aqueous medium

In the present manuscript, we have shown controlled release of an anticancer drug doxorubicin (Dox) from metal organic framework-drug composite under different external stimuli. We used 1, 3, 5, benzenetricarboxylic acid (H3BTC) as organic ligand and iron acetate and zinc nitrate as metals sources to synthesize FeBTC and ZnBTC MOFs which are known to be biocompatible. The in situ formation of MOF-drug composites demonstrates high drug loading capacity as compared to other conventional methods. The present methodology is devoid of extra steps for drug loading after synthesis. Moreover, the drug loading is also independent of pore size of the MOF as the drug molecules are embedded inside MOF during in situ formation of MOF. The drug release was monitored under external stimuli such as acidic pH and biocompatible liposomes for a period of more than 72 hours. The steady state fluorescence spectroscpy was used to monitor the drug release as a function of time and confocal laser scanning microscopy (CLSM) was used to unravel the post release fate of Dox in presence of liposomes. We found that drug release rateis higher for Zn-BTC-Dox composite than for Fe-BTC-Dox composite.This is attributed to the stronger binding betweenDOX and Fe-BTC than that between DOX and Zn-BTC. The study highlights a novel approach for the preparaion of MOF-drug composites in aqueous medium for the future biomedical application.

[Article]
ANJAN CHAKRABORTY, Chandan Adhikari
ChemPhysChem, January 11, 2016, DOI: 10.1002/cphc.201501012. Read article

Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

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).

[Communication]
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.

A Divalent PAMAM-Based Matrix Metalloproteinase/Carbonic Anhydrase Inhibitor for the Treatment of Dry Eye Syndrome

A Divalent PAMAM-Based Matrix Metalloproteinase/Carbonic Anhydrase Inhibitor for the Treatment of Dry Eye Syndrome

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.

[Full Paper]
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.

Controlled Multi-functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells

Controlled Multi-functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells

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.

[Full Paper]
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.

Ruthenium-Containing Block Copolymer Assemblies: Red-Light-Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy

Ruthenium‐Containing Block Copolymer Assemblies: Red‐Light‐Responsive Metallopolymers with Tunable Nanostructures for Enhanced Cellular Uptake and Anticancer Phototherapy

Self-assembled nanostructures of red-light-responsive Ru(II)-containing block copolymers are used for anticancer photo­therapy. The Ru complexes in the block copolymers are photocleavable and anticancer agents. Red light releases the Ru complexes and generates singlet oxygen in cancer cells. A moderate irradiation dose, which prevents photodamage, is sufficient to inhibit the growth of cancer cells.

[Full Paper]
Wen Sun, Maria Parowatkin, Werner Steffen, Hans-Jürgen Butt, Volker Mailänder, Si Wu
Adv. Healthcare Mater., December 17, 2015, DOI: 10.1002/adhm.201500827. Read article

Glutathione Bioresponsive Cyclodextrin Nanosponges

Glutathione Bioresponsive Cyclodextrin Nanosponges

Cyclodextrin-based nanosponges: A new one-step synthetic route for the production of glutathione (GSH)-responsive nanosponges was reported. The system can encapsulate the anticancer drug doxorubicin and release it as a function of external GSH concentration. In vitro and in vivo studies showed an increase in effectiveness of anticancer drugs encapsulated within the nanosponge (see figure).

[Communication]
Francesco Trotta, Fabrizio Caldera, Chiara Dianzani, Monica Argenziano, Giuseppina Barrera, Roberta Cavalli
ChemPlusChem, December 15, 2015, DOI: 10.1002/cplu.201500531. Read article

Coordination Polymers Derived from Non-Steroidal Anti-Inflammatory Drugs for Cell Imaging and Drug Delivery

Coordination Polymers Derived from Non-Steroidal Anti-Inflammatory Drugs for Cell Imaging and Drug Delivery

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).

[Full Paper]
Mithun Paul, Parthasarathi Dastidar
Chem. Eur. J., December 11, 2015, DOI: 10.1002/chem.201503706. Read article.

Near-Infrared Light-Triggered Intracellular Delivery of Anticancer Drugs Using Porous Silicon Nanoparticles Conjugated with IR820 Dyes

Near‐Infrared Light‐Triggered Intracellular Delivery of Anticancer Drugs Using Porous Silicon Nanoparticles Conjugated with IR820 Dyes

Porous silicon nanoparticles conjugated with IR820 dyes trigger excellent intracellular drug release with near-infrared laser irradiation.

[Full Paper]
Bing Xia, Bin Wang, Zhenyu Chen, Qi Zhang, Jisen Shi
Adv. Mater. Interfaces, December 10, 2015, DOI: 10.1002/admi.201500715. Read article

Gelatin-Assisted Synthesis of Vaterite Nanoparticles with Higher Surface Area and Porosity as Anticancer Drug Containers In Vitro

Gelatin‐Assisted Synthesis of Vaterite Nanoparticles with Higher Surface Area and Porosity as Anticancer Drug Containers In Vitro

Holey vaterite nanoparticles! Porous vaterite nanoparticles (VNs) fabricated with gelatin assistance displayed high surface area and improved stability in aqueous solution. Their application as doxorubicin containers and their therapeutic efficacy against cancer cells were investigated in vitro. The vaterite nanoparticles prove to be excellent containers for anticancer drugs after modification by folic acid.

[Full Paper]
Anhe Wang, Yang Yang, Xiaoming Zhang, Xingcen Liu, Wei Cui, Junbai Li
ChemPlusChem, November 24, 2015, DOI: 10.1002/cplu.201500515. Read article

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