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Targeted drug delivery

Anders Lundgren, Björn Agnarsson, Ronald Zirbs, Vladimir P Zhdanov, Erik Reimhult, Fredrik Höök
Emerging biomedical applications such as molecular imaging and drug delivery often require directed binding of nanoparticles to cell-membrane receptors. The specific apparent affinity of such ligand-functionalized particles is size-dependent, an observation so far solely attributed to multivalent receptor-ligand interaction. We question the universality of this explanation by demonstrating that the binding kinetics also depends on weak, attractive colloidal-type interaction between nanoparticles and a lipid membrane...
October 26, 2016: ACS Nano
Mohammad A Kaisar, Ravi K Sajja, Shikha Prasad, Vinay V Abhyankar, Taylor Liles, Luca Cucullo
The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered: This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies...
October 26, 2016: Expert Opinion on Drug Discovery
Subhajit Ghosh, Saswat Mohapatra, Anisha Thomas, Debmalya Bhunia, Abhijit Saha, Gaurav Das, Batakrishna Jana, Surajit Ghosh
An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics, competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find out such a unique nanocarrier and engineer all the above-mentioned features into it. In this manuscript, we have shown for the first time that Apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc) and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation...
October 26, 2016: ACS Applied Materials & Interfaces
T L Rodgers, J E Magee, T Amure, F R Siperstein
The dynamics of co-polymer systems play an important role in the preparation and stability of formulations, as well as on their capability to function in drug delivery systems. Micelle inversion can occur as a result of a change in concentration when a solvent is very volatile and evaporates, or as a result of a change in solvent quality upon addition of another solvent to the original solution, or upon changes in pH. In this work, dissipative particle dynamics (DPD) is used to examine the dynamics of micelle inversion in concentrated systems of diblock and triblock amphiphiles, where interactions between neighboring aggregates are observed...
October 26, 2016: Soft Matter
Gangliang Huang, Yang Liu, Hualiang Huang
Synthetic lipoprotein is an effective carrier of targeted delivery for drugs, chemicals, and so on. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptor-binding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits excellent characteristics in drug delivery. Herein, the preparation methods, applications and the limited applications' solutions of synthetic lipoproteins as drug carriers were summarized...
October 24, 2016: Current Medicinal Chemistry
Saket Kumar Singh, Bibhas Kumar Bhunia, Nandana Bhardwaj, Sween Gilotra, Biman B Mandal
Tunable repeated drug administration is often inevitable in number of pathological cases. Reloadable 3D matrices for sustained drug delivery are predicted as a prospective avenue to realize this objective. This study was directed towards sonication-induced fabrication of novel reloadable Bombyx mori silk fibroin (SF) (4, 6 and 8 wt%) hydrogel, injected within 3D porous (8 wt%) scaffolds. The focus was to develop a dual-barrier reloadable depot system for sustained molecular cargo-release. Both the varying SF concentration (4, 6 and 8 wt%) and the sonication time (30, 45 and 60 s) dictated the extent of cross-linking, β-sheet content and porosity (1-10 µm) influencing the release behavior of model molecules...
October 26, 2016: Molecular Pharmaceutics
Yoonjee C Park, Chentian Zhang, Sudong Kim, Graciela Mohamedi, Carl Beigie, Jon O Nagy, R Glynn Holt, Robin O Cleveland, Noo Li Jeon, Joyce Y Wong
Microbubbles have been used in ultrasound-assisted drug delivery to help target solid tumors via blood vessels in vivo; however, studies to understand the phenomena at the cellular level and to optimize parameters for ultrasound or microbubbles in vivo are challenging and expensive to perform. Here, we utilize microfluidic microvessels-on-a-chip that enable visualization of microbubble/ultrasound-dependent drug delivery to microvasculature. When exposed to pulsed ultrasound, microbubbles perfused through microvessels-on-a-chip were observed to stably oscillate...
October 26, 2016: ACS Applied Materials & Interfaces
Jakarwan Yostawonkul, Suvimol Surassmo, Tawin Iempridee, Wittaya Pimtong, Kunat Suktham, Warayuth Sajomsang, Pattarapond Gonil, Uracha Rungsardthong Ruktanonchai
A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200-400nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE>90%)...
September 29, 2016: Colloids and Surfaces. B, Biointerfaces
Egor Bobrov, Natalia Skobeleva, Diana Restifo, Natalya Beglyarova, Kathy Q Cai, Elizabeth Handorf, Kerry Campbell, David A Proia, Vladimir Khazak, Erica A Golemis, Igor Astsaturov
The lack of effective treatment modalities is a major problem in pancreatic cancer (PCa), a devastating malignancy that is nearly universally driven by the "undruggable" KRAS and TP53 cancer genes. Poor tumor tissue penetration is the major source of resistance in pancreatic cancer where chemotherapy is the mainstay of treatment. In this study we exploited the selective tumor-targeting properties of the heat shock 90 protein inhibitors as the vehicle for drug delivery to pancreatic tumor tissues. STA-12-8666 is a novel esterase-cleavable conjugate of an HSP90i and a topoisomerase I inhibitor, SN-38...
October 13, 2016: Oncotarget
Hun-Jae Jang, Seonggu Yeo, Jack J Yoh
BACKGROUND AND AIMS: For conventional needless injection, there still remain many unresolved issues such as the potential for cross-contamination, poor reliability of targeted delivery dose, and significantly painstaking procedures. As an alternative, the use of microjets generated with Er:YAG laser for delivering small doses with controlled penetration depths has been reported. In this study, a new system with two stages is evaluated for effective transdermal drug delivery. First, the skin is pre-ablated to eliminate the hard outer layer and second, laser-driven microjet penetrates the relatively weaker and freshly exposed epidermis...
October 25, 2016: Lasers in Surgery and Medicine
Hassan Bardania, Seyed Abbas Shojaosadati, Farzad Kobarfard, Farid Dorkoosh, Marjan Esfahani Zadeh, Mahmoud Naraki, Mehrdad Faizi
Eptifibatide is an antiplatelet drug used for the treatment of thrombosis. However, as a result of its accumulation in non-targeted tissues and short half-life, it has a limited efficacy. In this study, RGD-modified nano-liposomes (RGD-MNL) were prepared as carriers for the targeted delivery of eptifibatide to activated platelets. The nano-liposomes were about 90 ± 10 nm in size, with an encapsulation efficiency of 37 ± 5 % and a good stability during 21 days, with a negligible change in the size of nanoliosomes...
October 24, 2016: Journal of Thrombosis and Thrombolysis
Cristina Prat, Alicia Lacoma
BACKGROUND: Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of resistance and the emergence of opportunistic pathogens that substitute the indigenous microbiota. METHODS: This review explores the major challenges and lines of research to adequately establish the clinical role of bacteria and the indications for antimicrobial treatment, and reviews novel therapeutic approaches...
October 2016: International Journal of Infectious Diseases: IJID
A C Sampaio, R J Mendes, P G Castro, A M Silva
Solid lipid nanoparticles (SLNs) are used as carriers for drug delivery, and are high biocompatible and designed to endure in the host organism. Despite its current industrial production is low, many of these substances are available on the market, and much more are in the production pipeline. As a result, many of them will end in aquatic systems raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Microbial decomposers of plant litter, play a key role in forested streams being responsible for the energy flow between terrestrial and aquatic environments...
October 21, 2016: Ecotoxicology and Environmental Safety
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Yu Zhang, Yifei Lu, Feng Wang, Sai An, Yujie Zhang, Tao Sun, Jianhua Zhu, Chen Jiang
Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l-form and d-form [des-Arg(10) ]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together...
October 24, 2016: Small
Jun-Qing Situ, Xiao-Juan Wang, Xiu-Liang Zhu, Xiao-Ling Xu, Xu-Qi Kang, Jing-Bo Hu, Chen-Ying Lu, Xiao-Ying Ying, Ri-Sheng Yu, Jian You, Yong-Zhong Du
Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL(-1) and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI...
October 24, 2016: Scientific Reports
María Luján Cuestas
Since the British scientist Michael Houghton along with George Kuo, Qui-Lim Choo (Chiron Corporation Emeryville), and Daniel W. Bradley (Centers for Disease Control and Prevention) co-discovered the causative agent of hepatitis C in 1989, so much progress has been made for the screening of blood donors and management of this chronic liver disease. In this regard, direct-acting antiviral agents (DAAs) have emerged as the potential "cure" of this slowly progressing and devastating disease. However, improvements are still clearly required since the anti-hepatitis C drugs currently available in the market are so extremely expensive (i...
October 19, 2016: Mini Reviews in Medicinal Chemistry
Shaghayegh Fathi, Adegboyega K Oyelere
Liposomes are biodegradable and biocompatible self-forming spherical lipid bilayer vesicles. They can encapsulate and deliver one or more hydrophobic and hydrophilic therapeutic agents with poor therapeutic indices to tumor sites. Properties such as lipid bilayer fluidity, charge, size and surface hydration can be modified to extend liposome circulation time in the bloodstream and enhance efficacy. The focus of this review is on ligand-conjugated liposomes and their potential application in tumor-targeted delivery...
October 24, 2016: Future Medicinal Chemistry
Mahfoozur Rahman, Sarwar Beg, Amita Verma, Fahad A Al Abbasi, Firoz Anwar, Sumant Saini, Sohail Akhter, Vikas Kumar
OBJECTIVES: The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed. KEY FINDINGS: Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOXs) and arachidonic acid (AA)...
October 24, 2016: Journal of Pharmacy and Pharmacology
Sen Lin, Tong Li, Peiling Xie, Qing Li, Bailiang Wang, Lei Wang, Lingli Li, Yuqin Wang, Hao Chen, Kaihui Nan
Targeted delivery of cytotoxic drugs to tumour tissue has great importance for successful chemotherapy. Legumain is an asparaginyl endopeptidase that is highly up-regulated in a number of solid tumours. The aim of this work was to prepare a novel hyaluronic acid (HA) based legumain sensitive nanogel for the delivery of doxorubicin with a high targeting efficiency both in vitro and in vivo. The legumain sensitive property is achieved by the conjugation of doxorubicin with HA via a legumain substrate peptide bridge...
October 24, 2016: Nanoscale
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