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Journal of Controlled Release: Official Journal of the Controlled Release Society

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https://www.readbyqxmd.com/read/30227159/using-elongated-microparticles-to-enhance-tailorable-nanoemulsion-delivery-in-excised-human-skin-and-volunteers
#1
Miko Yamada, Hossam Tayeb, Hequn Wang, Nhung Dang, Yousuf H Mohammed, Sam Osseiran, Paul J Belt, Michael S Roberts, Conor L Evans, Frank Sainsbury, Tarl W Prow
This study demonstrates, for the first time, clinical testing of elongated silica microparticles (EMP) combined with tailorable nanoemulsions (TNE) to enhance topical delivery of hydrophobic drug surrogates. Likewise, this is the first report of 6-carboxyfluorescein (a model molecule for topically delivered hydrophobic drugs) AM1 & DAMP4 (novel short peptide surfactants) used in volunteers. The EMP penetrates through the epidermis and stop at the dermal-epidermal junction (DEJ). TNE are unusually stable and useful because the oil core allows high drug loading levels and the surface properties can be easily controlled...
September 15, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30227158/conversion-of-a-soluble-diazepam-prodrug-to-supersaturated-diazepam-for-rapid-intranasal-delivery-kinetics-and-stability
#2
Davin Rautiola, James C Cloyd, Ronald A Siegel
The low aqueous solubility of diazepam (DZP) presents a challenge in formulating nasal sprays without the use of organic solvents. One approach to overcome this challenge involves co-administration of a soluble prodrug, avizafone (AVF), with a converting enzyme to produce supersaturated DZP at the site of administration. In addition to overcoming solubility issues, the supersaturated state of DZP provides an increased driving force for enhanced permeation across nasal mucosa. However, supersaturated solutions are metastable, and there is a limit to the degree of supersaturation (S) that can be reached without causing spontaneous phase separation of the solute...
September 15, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30223045/novel-glucosylceramide-synthase-inhibitor-based-prodrug-copolymer-micelles-for-delivery-of-anticancer-agents
#3
Jieni Xu, Whenchen Zhao, Jingjing Sun, Yixian Huang, Pengcheng Wang, Raman Venkataramanan, Da Yang, Xiaochao Ma, Ajay Rana, Song Li
In order to improve the efficacy of chemotherapy for cancers, we have developed a novel prodrug micellar formulation to co-deliver ceramide-generating anticancer agents and ceramide degradation inhibitor (PPMP). The prodrug nanocarrier is based on a well-defined POEG-b-PPPMP diblock copolymer. The hydrophilic block of POEG-b-PPPMP is POEG, and the hydrophobic block is composed of a number of PPMP units, which could work synergistically with loaded anticancer drugs. POEG-b-PPPMP was readily synthesized via a one-step reversible addition-fragment transfer (RAFT) polymerization from a PPMP monomer...
September 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30223044/immunoengineering-through-cancer-vaccines-a-personalized-and-multi-step-vaccine-approach-towards-precise-cancer-immunity
#4
REVIEW
Lien Lybaert, Karim Vermaelen, Bruno G De Geest, Lutz Nuhn
During the last decade anti-tumor immune-therapy has opened novel opportunities to efficiently combat cancer progression. The introduction of DC- and CAR T-cell based therapies as well as the successful application of antibody-based inhibitor of immune checkpoints (CTLA-4, PD1 and PDL1) have boosted the field and led to an overall benefit for many patients. In situ cancer vaccination is an attractive strategy to further improve the therapeutic outcome, especially towards a more personalized and individually tailored immune response against the patient's mutanome...
September 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30223043/recent-advances-in-applying-nanotechnologies-for-cancer-immunotherapy
#5
REVIEW
Reza Mahjub, Sukhdeep Jatana, Suen Ern Lee, Zhu Qin, Griffin Pauli, Meysam Soleimani, Soheil Madadi, Shyh-Dar Li
Cancer immunotherapy aimed at boosting cancer-specific immunoresponses to eradicate tumor cells has evolved as a new treatment modality. Nanoparticles incorporating antigens and immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance antitumor immunity. The nanotechnology approach has been demonstrated to be superior to standard formulations in in-vivo settings. In this article, we focus on recent advances made within the last 5 years in nanoparticle-based cancer immunotherapy, including peptide- and nucleic acid-based nanovaccines, nanomedicines containing an immunoadjuvant to activate antitumor immunity, nanoparticle delivery of immune checkpoint inhibitors and the combination of the above approaches...
September 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30219279/therapeutic-inhibition-of-spleen-tyrosine-kinase-in-inflammatory-macrophages-using-plga-nanoparticles-for-the-treatment-of-non-alcoholic-steatohepatitis
#6
Dhadhang Wahyu Kurniawan, Arun Kumar Jajoriya, Garima Dhawan, Divya Mishra, Josepmaria Argemi, Ramon Bataller, Gert Storm, Durga Prasad Mishra, Jai Prakash, Ruchi Bansal
Non-alcoholic steatohepatitis (NASH) is the leading cause of cirrhosis worldwide and the most rapidly growing indication for liver transplantation. Macrophages are the important cellular component in the inflammatory milieu in NASH. Inflammatory and pro-fibrotic mediators produced by macrophages causes significant tissue injury in many inflammatory diseases. Therefore, inhibition of the inflammatory macrophages would be a promising approach to attenuate NASH. In this study, we studied the implication of SYK pathway in NASH, and investigated PLGA nanoparticles-based delivery of SYK pathway inhibitor as an effective and promising therapeutic approach for the treatment of NASH...
September 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30219278/combined-encapsulation-of-a-tumor-antigen-and-immune-cells-using-a-self-assembling-immunostimulatory-dna-hydrogel-to-enhance-antigen-specific-tumor-immunity
#7
Yuka Umeki, Masaaki Saito, Kosuke Kusamori, Mari Tsujimura, Moeka Nishimura, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Our previous study demonstrated that the incorporation of a tumor antigen into a self-assembling DNA hydrogel, comprised of a DNA containing un-methylated cytosine-phosphate-guanine (CpG) dinucleotides (CpG DNA), efficiently induced antigen-specific tumor immunity after intra-tumoral injection into tumor-bearing mice. We hypothesized that the additional incorporation of immune cells, the target for the antigen and immunostimulatory CpG DNA, would increase the antitumor response. To prove this, immune cells were also encapsulated into the CpG DNA hydrogel and delivered along with the antigen...
September 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30219277/delivering-all-in-one-antigen-nanocapsule-loaded-with-dual-adjuvant-yields-superadditive-effects-by-dc-directed-t-cell-stimulation
#8
David Paßlick, Keti Piradashvili, Denise Bamberger, Mengyi Li, Shuai Jiang, Dennis Strand, Peter Wich, Katharina Landfester, Matthias Bros, Stephan Grabbe, Volker Mailänder
Therapeutic vaccination is and remains a major challenge, particularly in cancer treatment. In this process, the effective activation of dendritic cells by a combination of distinctly acting adjuvants and an antigen is crucial for success. While most common vaccine formulations lack the efficiency to trigger sufficient T cell responses in a therapeutic tumor treatment, nanovaccines offer unique properties to tackle that challenge. Here, we report the stepwise development of a nanocapsule for vaccination approaches, comprising a shell consisting of antigen and loaded with a superadditive adjuvant combination...
September 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30218687/advax-augments-b-and-t-cell-responses-upon-influenza-vaccination-via-the-respiratory-tract-and-enables-complete-protection-of-mice-against-lethal-influenza-virus-challenge
#9
Jasmine Tomar, Harshad P Patil, Gustavo Bracho, Wouter F Tonnis, Henderik W Frijlink, Nikolai Petrovsky, Rita Vanbever, Anke Huckriede, Wouter L J Hinrichs
Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5 μm) suitable for inhalation...
September 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30217739/light-enhanced-vegf-121-rgel-a-tumor-targeted-modality-with-vascular-and-immune-mediated-efficacy
#10
Anette Weyergang, Ane S Fremstedal, Ellen Skarpen, Qian Peng, Khalid A Mohamedali, Marius S Eng, Lawrence H Cheung, Michael G Rosenblum, Johannes Waltenberger, Kristian Berg
Interactions between stromal cells and tumor cells pay a major role in cancer growth and progression. This is reflected in the composition of anticancer drugs which includes compounds directed towards the immune system and tumor-vasculature in addition to drugs aimed at the cancer cells themselves. Drug-based treatment regimens are currently designed to include compounds targeting the tumor stroma in addition to the cancer cells. Treatment limiting adverse effects remains, however, one of the major challenges for drug-based therapy and novel tolerable treatment modalities with diverse high efficacy on both tumor cells and stroma is therefore of high interest...
September 11, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30194947/an-intestinal-paracellular-pathway-biased-toward-positively-charged-macromolecules
#11
Khaled Almansour, Alistair Taverner, Jerrold R Turner, Ian M Eggleston, Randall J Mrsny
Lacking an effective mechanism to safely and consistently enhance macromolecular uptake across the intestinal epithelium, prospects for successful development of oral therapeutic peptide drugs remain unlikely. We previously addressed this challenge by identifying an endogenous mechanism that controls intestinal paracellular permeability that can be activated by a peptide, termed PIP 640, which can increase cellular levels of phosphorylated myosin light chain at position S19 (MLC-pS19 ). Apical application in vitro or luminal application in vivo was shown to increase macromolecular solute transport within minutes that recovered completely within a few hours after removal...
September 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30194946/nir-light-and-gsh-activated-cytosolic-p65-shrna-delivery-for-precise-treatment-of-metastatic-cancer
#12
Feihu Wang, Qian Huang, Yun Wang, Leilei Shi, Yuanyuan Shen, Shengrong Guo
Despite advances in cancer therapy, metastasis remains the dominate reason for cancer-related mortality. Herein, a novel, hybrid nanocomplex, RDG/shRNA, with tumor-targeting and dual stimuli responsive properties is described for the effective treatment of metastatic cancer. This multimodal therapeutic system was prepared by complexing RDG nanovectors with p65-shRNA, an anti-NF-κB agent, via the electrostatic interactions between negatively charged shRNA and the cationic DSPEI displayed on the surface of the nanovectors...
September 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30189223/preparation-properties-and-challenges-of-the-microneedles-based-insulin-delivery-system
#13
REVIEW
Xiang Chen, Li Wang, Haojie Yu, Chengjiang Li, Jingyi Feng, Fazal Haq, Amin Khan, Rizwan Ullah Khan
Microneedle technology relates to pharmacy, polymer chemistry and micromachining. Microneedle can effectively deliver insulin into systemic circulation across the skin. This process does not affect the activity of insulin. Compared to subcutaneous injection, microneedles cause less pain for their special structure. This review thoroughly discusses the preparation technologies of the microneedles-based insulin delivery system including solid, hollow, dissolving, phase transition, glucose-responsive microneedle patches...
September 3, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30184466/cancer-stem-cells-emanated-therapy-resistance-implications-for-liposomal-drug-delivery-systems
#14
REVIEW
Hassan Dianat-Moghadam, Maryam Heydarifard, Rana Jahanban-Esfahlan, Yunes Panahi, Hamed Hamishehkar, Farhad Pouremamali, Reza Rahbarghazi, Mohammad Nouri
It is verified that failure in cancer therapy by conventional chemotherapeutic agents arise from cancer heterogeneity. That, a small subpopulation of cancer cells known as "cancer stem cells" (CSCs) are shown to be responsible for deriving clonal heterogeneity/diversity in tumors, which render them resistant to conventional treatment regimes. So far, efficient targeted cancer therapy by nanotechnology-based drug delivery approaches is well established. Among various introduced nanocarriers, the non-toxic nature and biocompatibility of liposome make it highly desirable for human studies...
September 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30184465/drug-nanocrystallisation-within-liposomes
#15
REVIEW
Tang Li, David Cipolla, Thomas Rades, Ben J Boyd
Liposomes are phospholipid bilayer vesicles that have been explored in pharmaceutical research as drug delivery systems for >50 years. Despite being important to their morphology and drug release pattern, the physical state of the drug within liposomes (liquid, solid, crystalline form) is often overlooked. This review focuses on precipitation of drug within liposomes, which can result in the formation of confined nanocrystals, and consequent changes in liposome morphology and drug release patterns. The type of drugs that form nanocrystals within liposomes, preparation and characterisation of liposomal drug nanocrystals, and the in vitro drug release behaviour from these systems are communicated, with a discussion of their potential as drug delivery systems...
September 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30172673/affibody-derived-drug-conjugates-potent-cytotoxic-molecules-for-treatment-of-her2-over-expressing-tumors
#16
Mohamed Altai, Hao Liu, Haozhong Ding, Bogdan Mitran, Per-Henrik Edqvist, Vladimir Tolmachev, Anna Orlova, Torbjörn Gräslund
Patients with HER2-positive tumors often suffer resistance to therapy, warranting development of novel treatment modalities. Affibody molecules are small affinity proteins which can be engineered to bind to desired targets. They have in recent years been found to allow precise targeting of cancer specific molecular signatures such as the HER2 receptor. In this study, we have investigated the potential of an affibody molecule targeting HER2, ZHER2:2891 , conjugated with the cytotoxic maytansine derivate MC-DM1, for targeted cancer therapy...
August 30, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30171978/encapsulation-of-thermo-responsive-gel-in-ph-sensitive-polymersomes-as-dual-responsive-smart-carriers-for-controlled-release-of-doxorubicin
#17
Fatemeh Oroojalian, Maryam Babaei, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, Mona Alibolandi
In the current study, thermoresponsive poly(N-isopropylacrylamide)-doxorubicin (PNIPAM-DOX) hydrogel was synthesized and loaded into pH-responsive poly ethylene glycol)-2,4,6- trimethoxy benzylidene pentaerythritol carbonate (PEG-PTMBPEC) polymersomes in order to fabricate a smart thermo-pH stimuli responsive drug delivery system. Thermo-pH responsive polymersomal formulation of DOX revealed average size of 170 ± 11.2 nm. The prepared system was loaded with PNIPAM-DOX conjugate with encapsulation efficiency of 30...
August 30, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30171979/novel-hydrophilic-matrix-system-with-non-uniform-drug-distribution-for-zero-order-release-kinetics
#18
Matteo Cerea, Alessandra Maroni, Luca Palugan, Marco Bellini, Anastasia Foppoli, Alice Melocchi, Lucia Zema, Andrea Gazzaniga
A decrease in the release rate over time is typically encountered when dealing with hydrophilic matrix systems for oral prolonged release due to progressive increase of the distance the drug molecules have to cover to diffuse outwards and reduction of the area of the glassy matrix at the swelling front. In order to solve this issue, a novel formulation approach based on non-uniform distribution of the active ingredient throughout the swellable polymer matrix was proposed and evaluated. Various physical mixtures of polymer (high-viscosity hypromellose) and drug tracer (acetaminophen), having decreasing concentrations of the latter, were applied by powder-layering onto inert core seeds...
August 29, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30171977/a-tumor-targeted-near-infrared-light-controlled-nanocomposite-to-combat-with-multidrug-resistance-of-cancer
#19
Meng Wang, Jiahe Wu, Ying Li, Fangyuan Li, Xi Hu, Gang Wang, Min Han, Daishun Ling, Jianqing Gao
Stimuli-responsive nanomaterials have emerged as promising drug delivery systems for tumor therapy, as they can specifically respond to tumor-associated stimuli and release the loaded drugs in a controllable manner. However, most currently available stimuli-responsive nanomedicines rely on surrounding extreme stimulus to trigger the activity, which can be inefficient under dynamic and complex living conditions. Herein, we report a near-infrared (NIR) light-responsive nanocomposite, which can generate reactive oxygen species to efficiently trigger the decomposition upon NIR laser irradiation...
August 29, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30170067/hyaluronic-acid-endostatin2-alft1-ha-es2-af-nanoparticle-like-conjugate-for-the-target-treatment-of-diseases
#20
Feng Sun, Yang Yu, Zhifang Yang, Zhendong Wang, Yan Li, Fengshan Wang, Haining Tan
Anti-flt1 peptide (GNQWFI, AF) specifically binds to Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), thereby inhibiting the interaction of VEGFR1 with a series of ligands. ES2 (IVRRADRAAVP) can effectively inhibit the proliferation and invasion of endothelial cells and play a key role in anti-angiogenesis. AF and ES2 peptides differ in their activity. To better exploit the advantages of both, we designed a new peptide called ES2-AF (IVRRADRAAVPGGGGGGNQWFI). Hyaluronic acid (HA) is widely used in the pharmaceutical industry because of its biodegradable and high load performance...
August 29, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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