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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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Linear, Star, and Comb Oxidation-Responsive Polymers: Effect of Branching Degree and Topology on Aggregation and Responsiveness

Linear, Star, and Comb Oxidation‐Responsive Polymers: Effect of Branching Degree and Topology on Aggregation and Responsiveness

The oxidative response of polysulfides can be retarded by an appropriate choice of branching degree and topology.

[Communication]
Richard d'Arcy, Arianna Gennari, Roberto Donno, Nicola Tirelli
Macromol. Rapid Commun., September 27, 2016, DOI: 10.1002/marc.201600481. Read article

Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales

Breaching the Hyaluronan Barrier with PH20‐Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales

Intratumoral delivery of typical therapeutic agents (doxorubicin, trastuzumab, and pegylated gold nanorods) can be significantly enhanced by degrading tumor microenvironment component hyaluronan with long-acting hyaluronidase PH20-Fc. Meanwhile, the performance of PH20-Fc varies among these three therapeutic agents due to ther different nanoscales, and Tmab benefits most in penetration and accumulation.

[Full Paper]
Shan Liu, Wei Wei, Bo Xie, Hua Yue, Dezhi Ni, Yali Bao, Guanghui Ma, Zhiguo G. Su
Adv. Healthcare Mater., September 27, 2016, DOI: 10.1002/adhm.201600528. Read article

Mucus-Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces

Mucus‐Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces

Mucus-penetrating nanosuspensions, consisting of pure hydrophobic therapeutics with dense muco-inert coatings that enable particles to effectively bypass the mucus barrier, demonstrate superior drug distribution and absorption at mucosal surfaces. With significantly increased drug load compared to polymeric systems and established clinical translation of nanosuspensions-based products, mucus-penetrating nanosuspensions are a promising vehicle for improving mucosal delivery of poorly soluble drugs.

[Communication]
Tao Yu, Jane Chisholm, Woo Jin Choi, Abraham Anonuevo, Sarah Pulicare, Weixi Zhong, Minmin Chen, Colleen Fridley, Samuel K. Lai, Laura M. Ensign, Jung Soo Suk, Justin Hanes
Adv. Healthcare Mater., September 26, 2016, DOI: 10.1002/adhm.201600599. Read article

Unprecedented “All-in-One” Lanthanide-Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo-Photodynamic Therapy of Tumors

Unprecedented “All‐in‐One” Lanthanide‐Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo‐Photodynamic Therapy of Tumors

Unprecedented all-in-one multifunctional lanthanide-doped mesoporous silica frameworks (EuGdOx@MSF) are used for bimodal fluorescence/T1-magnetic resonance (MR) imaging and near infrared (NIR) light-triggered chemo-photodynamic therapy to completely destroy tumors. It is demonstrated that EuGdOx@MSF can sensitize formation of singlet oxygen upon NIR light excitation and exert nanomaterial-mediated photodynamic therapy effects without the need for externally added organic photosensitizers.

[Full Paper]
Poliraju Kalluru, Raviraj Vankayala, Chi-Shiun Chiang, Kuo Chu Hwang
Adv. Funct. Mater., September 26, 2016, DOI: 10.1002/adfm.201603749. Read article

Dual-Targeting Heparin-Based Nanoparticles that Re-Assemble in Blood for Glioma Therapy through Both Anti-Proliferation and Anti-Angiogenesis

Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

Nanoparticles (NPs) are formed when a heparin-based polymer containing two different peptides self-assembles in water. The peptides target different cell receptors, and their structures enable the NPs to rearrange and re-self-assemble in blood. Their dual-targeting capability and resulting size in blood make them suitable for in vivo brain drug delivery. By-passing the vascular–tumor barrier and accumulating specifically in glioma, these NPs exhibit an excellent anti-glioma effect in mice.

[Full Paper]
Jihui Wang, Yuantao Yang, Yonghong Zhang, Min Huang, Zhenjun Zhou, Wanxian Luo, Jiao Tang, Jianguo Wang, Qian Xiao, Huajian Chen, Yingqian Cai, Xinlin Sun, Ying Wang, Yiquan Ke
Adv. Funct. Mater., September 22, 2016, DOI: 10.1002/adfm.201602810. Read article

Quantum Dot-Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery

Quantum Dot‐Based Nanotools for Bioimaging, Diagnostics, and Drug Delivery

Joining the dots: Recent achievements in applications of quantum dots for in vitro and in vivo bioimaging, targeting, and drug delivery are reviewed. The issues of quantum dot toxicity and recent progress in overcoming this problem are also discussed.

[Review]
Regina Bilan, Igor Nabiev, Alyona Sukhanova
ChemBioChem, September 21, 2016, DOI: 10.1002/cbic.201600357. Read article

Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging-Monitored Drug Delivery

Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging‐Monitored Drug Delivery

Upconversion nanobeacon as a new theranostic nanoprobe to ratiometrically detect and visualize the TK1 mRNA that can simultaneously trigger the Dox release to activate the chemotherapy accordingly is demonstrated. The results reveal that the nanobeacons based on the ratiometric upconversion detection of tumor biomarkers may have great potential as precise theranostic agents for the noninvasive treatment of deep cancer.

[Full Paper]
Qianwen Ding, Qiuqiang Zhan, Xiaoming Zhou, Tao Zhang, Da Xing
Small, September 20, 2016, DOI: 10.1002/smll.201601724. Read article

Molecular Engineering of Somatostatin Analogue with Minimal Dipeptide Motif Induces the Formation of Functional Nanoparticles

Molecular Engineering of Somatostatin Analogue with Minimal Dipeptide Motif Induces the Formation of Functional Nanoparticles

Hormone analogue co-assembly: Introduction of a very simple dipeptide recognition module, diphenylalanine, induced the assembly of somatostatin analogue hybrid peptide to form nanospheres. Supramolecular co-polymers with this functional designed building block mixed with another diphenylalanine derivative were shown to efficiently bind to cancer cells and target tumors. The integrated new nanosystem could play a dual role of both a nanocarrier and a bioactive targeting component.

[Communication]
Talia Shekhter Zahavi, Mor Oron-Herman, Genady Kostenich, Eyal Rub, Yoseph Salitra, Ludmila Buzhansky, Arie Orenstein, Ehud Gazit, Lihi Adler-Abramovich
ChemNanoMat, September 15, 2016, DOI: 10.1002/cnma.201600220. Read article

The Silica-based Formulations for Drug Delivery, Bone Treatment, and Bone Regeneration

The Silica-based Formulations for Drug Delivery, Bone Treatment, and Bone Regeneration

This review presents the current state and perspectives of the controlled release of drugs, bone treatments, and bone regeneration using diverse silica-based materials excluding ordered mesoporous silica nanoparticles. It also discussed various in vitro and in vivo biological evaluations such as bio-mineralization, osteoblast cells adhesion and proliferation, osteogenetic performances and osteogenic differentiation.

[Review]
Mohammad A. Chowdhury
ChemBioEng Reviews, September 14, 2016, DOI: 10.1002/cben.201500026. Read article.

Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus

Engineered Nanoplatelets for Enhanced Treatment of Multiple Myeloma and Thrombus

A platelet membrane-coated biomimetic nanocarrier, which can sequentially target bone microenvironment and myeloma cells to enhance the drug availability at the myeloma site and decrease the off-target effects, is developed for inhibiting the multiple myeloma growth and simultaneously eradicating the thrombus complication.

[Communication]
Quanyin Hu, Chenggen Qian, Wujin Sun, Jinqiang Wang, Zhaowei Chen, Hunter N. Bomba, Hongliang Xin, Qundong Shen, Zhen Gu
Adv. Mater., September 14, 2016, DOI: 10.1002/adma.201603463. Read article

Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation

Multitriggered Tumor‐Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation

Protein-based nanospheres for smart drug delivery are developed through electrostatic assembly of proteins and polypeptides. Benefiting from the multiresponsiveness of the nanospheres to changes in pH, redox, and proteinase, the tumor-responsive release of photosensitizers from photosensitizer-loaded nanospheres is achieved in vivo, resulting in enhanced photodynamic tumor ablation.

[Full Paper]
Ning Zhang, Fenfang Zhao, Qianli Zou, Yongxin Li, Guanghui Ma, Xuehai Yan
Small, September 13, 2016, DOI: 10.1002/smll.201602339. Read article

PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors

PHB‐Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors

An injectable thermogel consisting of a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate], hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages shows localized delivery of chemotherapeutics in a minimally invasive approach and good controllable release effect against the in vivo model of tumors, which might be beneficial for better chemotherapy design and precision medicine.

[Full Paper]
Yun-Long Wu, Han Wang, Ying-Kun Qiu, Sing Shy Liow, Zibiao Li, Xian Jun Loh
Adv. Healthcare Mater., September 05, 2016, DOI: 10.1002/adhm.201600723. Read article

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

Multifunctional Mixed Micelles for Efficient Docetaxol Delivery for Cancer Therapy

Critical micelles concentrate on cancer: Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells.

[Full Paper]
Pei Zhang, Wenxiu He, Huiyuan Zhang, Chunzhi Huang, Dujuan Zhao, Yuxia Luan
ChemPlusChem, August 25, 2016, DOI: 10.1002/cplu.201600363. Read article

Benzoic-Imine-Based Physiological-pH-Responsive Materials for Biomedical Applications

Benzoic‐Imine‐Based Physiological‐pH‐Responsive Materials for Biomedical Applications

Block party: A dynamic covalent benzoic imine bond has been developed as a highly pH-sensitive building block for the construction of polymeric biomedical systems.

[Focus Review]
Xiaozhong Qu, Zhenzhong Yang
Chem. Asian J., August 18, 2016, DOI: 10.1002/asia.201600452. Read article

Acid-Labile Copolymer Micelles Cross-Linked by a Twin Ortho Ester Cross-Linking Agent: Synthesis, Characterization, and Evaluation

Acid‐Labile Copolymer Micelles Cross‐Linked by a Twin Ortho Ester Cross‐Linking Agent: Synthesis, Characterization, and Evaluation

In this paper, a series of poly(ethylene glycol)-block-poly(N-succinimidyl methacrylate) (PEG-b-PNSM) with different length of PNSM is synthesized and self-assembled to give non-cross-linked micelles. The cross-linked micelles (CLM) are obtained by adding a pH-sensitive cross-linker, 2-{4-[2-(2-amino-ethoxy)-[1,3] dioxolan-4-ylmethoxymethyl]-[1,3]dioxolan-2-yloxy}-ethylamine. PTX is incorporated into CLM, and released at accelerated rate under mildly acidic pH (pH = 5), resulting in an appropriate cytotoxicity against MCF-7 cells.

[Full Paper]
Xin Wang, Xiaojing Zhou, Jun Wang, Zhipeng Cao, Lei Zhang, Rupei Tang
Macromol. Chem. Phys., August 11, 2016, DOI: 10.1002/macp.201600234. Read article

Synthesis of Degradable Poly[(Ethylene Glycol)-co-(Glycolic Acid)] via the Post-Polymerization Oxyfunctionalization of Poly(Ethylene Glycol)

Synthesis of Degradable Poly[(Ethylene Glycol)‐co‐(Glycolic Acid)] via the Post‐Polymerization Oxyfunctionalization of Poly(Ethylene Glycol)

To enhance the limited degradability of poly(ethylene glycol) (PEG), a straightforward method of synthesizing poly[(ethylene glycol)-co-(glycolic acid)] is described. Hydrolytically labile ester groups are directly incorporated into the polymer backbone via a ruthenium catalyzed C–H oxyfunctionalization reaction with minimal molecular-weight reduction under some conditions. The method should facilitate access to a variety of degradable PEG platforms.

[Communication]
Di Liu, Christopher W. Bielawski
Macromol. Rapid Commun., July 27, 2016, DOI: 10.1002/marc.201600336. Read article

Simultaneously Photo-Cleavable and Activatable Prodrug-Backboned Block Copolymer Micelles for Precise Anticancer Drug Delivery

Simultaneously Photo‐Cleavable and Activatable Prodrug‐Backboned Block Copolymer Micelles for Precise Anticancer Drug Delivery

A simultaneously photo-cleavable and activatable prodrug-backboned block copolymer (BCP) micelle strategy is demonstrated. Without light treatment, the micelles stay silent and inactivated, being biocompatible to normal tissues. Concurrent chain cleavage of BCP micelles and the activation of Pt(IV) prodrug could be temporally and spatially triggered by UV or even visible light for precise anticancer drug delivery.

[Communication]
Dongfang Zhou, Jinshan Guo, Gloria B. Kim, Jizhen Li, Xuesi Chen, Jian Yang, Yubin Huang
Adv. Healthcare Mater., July 27, 2016, DOI: 10.1002/adhm.201600470. 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

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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