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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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Biodegradable Multiblock Polymers Based on N-(2-Hydroxypropyl)methacrylamide Designed as Drug Carriers for Tumor-Targeted Delivery

Biodegradable Multiblock Polymers Based on N‐(2‐Hydroxypropyl)methacrylamide Designed as Drug Carriers for Tumor‐Targeted Delivery

Polymer drug-carriers designed for tumor-targeted delivery are synthesized. High molecular-weight multiblock polymers based on N-(2-hydroxypropyl)methacrylamide are prepared via polycycloadittion reaction of azide and alkyne chain ends. These multiblock polymers contain peptide linkages, originating from chain transfer agents, which are degradable hydrolytically or enzymatically. In addition, multiblock polymers with azo-linkages susceptible to thermal degradation at elevated temperature are prepared.

[Full Paper]
Gabriela Mužíková, Robert Pola, Richard Laga, Michal Pechar
Macromol. Chem. Phys., June 27, 2016, DOI: 10.1002/macp.201600097. Read article

Stem Cell Membrane-Coated Nanogels for Highly Efficient In Vivo Tumor Targeted Drug Delivery

Stem Cell Membrane‐Coated Nanogels for Highly Efficient In Vivo Tumor Targeted Drug Delivery

Stem cell membrane-coated nanogels can effectively evade clearance of the immune system, enhance the tumor targeting properties and antitumor chemotherapy efficacy of gelatin nanogels loaded doxorubicin in mice.

[Communication]
Changyong Gao, Zhihua Lin, Beatriz Jurado-Sánchez, Xiankun Lin, Zhiguang Wu, Qiang He
Small, June 23, 2016, DOI: 10.1002/smll.201600624. Read article

Preparation of a Noncytotoxic Hemocompatible Ion Gel by Self-Polymerization of HEMA in a Green Deep Eutectic Solvent

Preparation of a Noncytotoxic Hemocompatible Ion Gel by Self‐Polymerization of HEMA in a Green Deep Eutectic Solvent

Self-polymerization of 2-hydroxyethylmethacrylate in a natural deep eutectic solvent in the presence of indomethacin resulted the formation of a drug-immobilized ion gel. The ion gel thus obtained is found to be stable in gastrointestinal fluid pH and sustained release in simulated lower intestinal fluid at physiological human body temperature of the drug is recorded.

[Full Paper]
Chandrakant Mukesh, Kapil K. Upadhyay, Ranjitsinh V. Devkar, Nishith A. Chudasama, Gopalkumar G. Raol, Kamalesh Prasad
Macromol. Chem. Phys., June 20, 2016, DOI: 10.1002/macp.201600122. Read article

Molecular Assembly of Polysaccharide-Based Microcapsules and Their Biomedical Applications

Molecular Assembly of Polysaccharide‐Based Microcapsules and Their Biomedical Applications

Advanced polysaccharide-based microcapsules have revealed great potential in biomedical applications owing to their tunable structure, surface properties, stimuli responsiveness, and remarkable biocompatibility. In this account, we summarize our investigations in multifunctional molecular assemblies including the principles of bioinspired design and fabrication, and further discuss the applications in biomedical areas.

[Personal Account]
Xiyun Feng, Cuiling Du, Junbai Li
The Chemical Record, June 16, 2016, DOI: 10.1002/tcr.201600051. Read article

A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens

A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens

A peptide hydrogel with an antimicrobial activity is developed as a bandage contact lens. The antimicrobial activity is enhanced with the addition of the biomolecules penicillin G or poly-ε-lysine and is positive against Staphylococcus aureus and Escherichia coli. The lens is also noncytotoxic toward a human corneal epithelial cell line and as a consequence is of great potential as a drug-eluting bandage lens replacing conventional corneal ulcer treatment.

[Communication]
Andrew G. Gallagher, Jamal A. Alorabi, Donald A. Wellings, Rebecca Lace, Mal J. Horsburgh, Rachel L. Williams
Adv. Healthcare Mater., June 08, 2016, DOI: 10.1002/adhm.201600258. Read article

Low Cytotoxic Metal–Organic Frameworks as Temperature-Responsive Drug Carriers

Low Cytotoxic Metal–Organic Frameworks as Temperature‐Responsive Drug Carriers

Drugs on demand: Two low cytotoxicity metal–organic frameworks (MOFs), ZJU-64 and ZJU-64-CH3, have been prepared. The anticancer drug methotrexate (MTX) can be loaded at desirable drug payloads. The drug-loaded crystals exhibit sustainable release and temperature-responsive deliveries to provide a new strategy that combines drug therapy and thermal therapy to advance the therapeutic efficacy (see figure).

[Full Paper]
Wenxin Lin, Quan Hu, Jiancan Yu, Ke Jiang, Yanyu Yang, Shengchang Xiang, Yuanjing Cui, Yu Yang, Zhiyu Wang, Guodong Qian
ChemPlusChem, June 06, 2016, DOI: 10.1002/cplu.201600142. Read article

Hybrid Nanoparticles as Drug Carriers for Controlled Chemotherapy of Cancer

Hybrid Nanoparticles as Drug Carriers for Controlled Chemotherapy of Cancer

Hybrid nanoparticles offer many opportunities for the optimization and improvement of conventional chemotherapy and have great potential in terms of improved biosafety, biocompatibility, multifunctionality, and biodegradability. This Personal Account highlights strategies currently available for the regulation of drug release from hybrid nanoparticle carriers.

[Personal Account]
Menghuan Li, Zhong Luo, Yanli Zhao
The Chemical Record, June 03, 2016, DOI: 10.1002/tcr.201600029. Read article

Folate-Conjugated Polylactic Acid–Silica Hybrid Nanoparticles as Degradable Carriers for Targeted Drug Delivery, On-Demand Release and Simultaneous Self-Clearance

Folate‐Conjugated Polylactic Acid–Silica Hybrid Nanoparticles as Degradable Carriers for Targeted Drug Delivery, On‐Demand Release and Simultaneous Self‐Clearance

Wait before removing your coat: A novel SiO2-based nanocarrier coated with polylactic acid and folate (FA) has been used to destroy tumors (see figure). This nanocomposite can target the delivery of doxorubicin (Dox) without premature leakage of the drug before the polylactic acid is degraded. Decomposition of the SiO2 carrier improves its clearance from biological tissues.

[Full Paper]
Zhifang Ma, Xiaolei Li, Xiaodan Jia, Jing Bai, Xiue Jiang
ChemPlusChem, June 02, 2016, DOI: 10.1002/cplu.201600100. Read article

Phospholipid End-Capped Acid-Degradable Polyurethane Micelles for Intracellular Delivery of Cancer Therapeutics

Phospholipid End‐Capped Acid‐Degradable Polyurethane Micelles for Intracellular Delivery of Cancer Therapeutics

Nanoscale drug carriers fabricated by phospholipid end-capped polyurethane bearing acetal backbones that degrade in acidic conditions are fabricated. These micelles effectively allow drugs to enter the blood circulation, and then disintegrate in acidic endosomes and lysosomes for intelligent delivery of payloads.

[Communication]
Johnson V. John, Reju George Thomas, Hye Ri Lee, Hongyu Chen, Yong Yeon Jeong, Il Kim
Adv. Healthcare Mater., June 01, 2016, DOI: 10.1002/adhm.201600126. Read article

Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry

Assessing the Delivery of Molecules to the Mitochondrial Matrix Using Click Chemistry

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.

[Communication]
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

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

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.

[Article]
Zuzanna Pietralik, Andrzej Skrzypczak, Maciej Kozak
ChemPhysChem, May 23, 2016, DOI: 10.1002/cphc.201600175. Read article

Molecular Polymer Brushes in Nanomedicine

Molecular Polymer Brushes in Nanomedicine

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.

[Talent]
Markus Müllner
Macromol. Chem. Phys., May 06, 2016, DOI: 10.1002/macp.201600086. Read article

Amphiphilic Triblock Copolymers from Poly(2-oxazoline) with Different Hydrophobic Blocks: Changes of the Micellar Structures upon Addition of a Strongly Hydrophobic Cancer Drug

Amphiphilic Triblock Copolymers from Poly(2‐oxazoline) with Different Hydrophobic Blocks: Changes of the Micellar Structures upon Addition of a Strongly Hydrophobic Cancer Drug

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.

[Full Paper]
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

Enhanced Efficacy of Artemisinin Loaded in Transferrin-Conjugated Liposomes versus Stealth Liposomes against HCT-8 Colon Cancer Cells

Enhanced Efficacy of Artemisinin Loaded in Transferrin‐Conjugated Liposomes versus Stealth Liposomes against HCT‐8 Colon Cancer Cells

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.

[Full Paper]
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

Albumin Nanoparticles for Brain Delivery: A Comparison of Chemical versus Thermal Methods and in vivo Behavior

Albumin Nanoparticles for Brain Delivery: A Comparison of Chemical versus Thermal Methods and in vivo Behavior

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.

[Full Paper]
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

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.

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.

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.

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