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Drug Delivery

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March 25, 2019: Drug Delivery
Xu Wan, Chaoqian Liu, Yinan Lin, Jie Fu, Guohong Lu, Zhengmao Lu
Although a variety of drug delivery strategies have been designed for enhancing the treatment of Triple negative breast cancer (TNBC), combating with TNBCs is still dramatically challenged by the selection of appropriate therapeutic targets and insufficient tumor accumulation or inner penetration of chemotherapeutics. To address these issues, the classical EGFR-inhibitor, erlotinib (EB), was selected as the model drug here and PLA-based nano-platform (NP-EB) was prepared for tumor site drug delivery. Given the significant role of Notch-EGFR interplay in raising severe resistance to EGFR inhibition of EB, gamma secretase inhibitor (GSI)-DAPT was further entrapped into the core of nanoparticles to inhibit the activation of Notch signaling (NP-EB/DART)...
December 2019: Drug Delivery
Mengshuang Li, Jie Lan, Xuefei Li, Meng Xin, Hui Wang, Fan Zhang, Xiaohong Lu, Zengfang Zhuang, Xianggen Wu
OBJECTIVES: Ginsenosides Rb1 (Rb1) could form micelles in aqueous solutions. Self-assembled Rb1 micelles could potentially be utilized as ocular drug delivery system, and it was postulated that the encapsulation of a medicine within Rb1 micelles might strengthen the drug's therapeutic action and reduce side effects. METHODS: Diclofenac-loaded Rb1 micelles (Rb1-Dic micelles) were formulated, optimized, and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vivo corneal permeation, and in vivo anti-inflammatory efficacy...
December 2019: Drug Delivery
Shirley Sharabi, Yael Bresler, Orly Ravid, Chen Shemesh, Dana Atrakchi, Michal Schnaider-Beeri, Fabien Gosselet, Lucie Dehouck, David Last, David Guez, Dianne Daniels, Yael Mardor, Itzik Cooper
The blood-brain barrier (BBB) is limiting transcellular and paracellular movement of molecules and cells, controls molecular traffic, and keeps out toxins. However, this protective function is the major hurdle for treating brain diseases such as brain tumors, Parkinson's disease, Alzheimer's disease, etc. It was previously demonstrated that high pulsed electrical fields (PEFs) can disrupt the BBB by inducing electroporation (EP) which increases the permeability of the transcellular route. Our goal was to study the effects of low PEFs, well below the threshold of EP on the integrity and function of the BBB...
December 2019: Drug Delivery
Alfredo Lucas, Dawn Lam, Pedro Cabrales
Doxorubicin (DOX) is one of the most widely used anticancer agents. DOX is known for inducing cardiotoxicity, resulting in the long-term development of heart failure. Intravascular delivery of DOX may benefit from the carriage by red blood cells (RBCs), as they can limit the systemic toxicity while delivering the DOX to the tumor. This study proposes a methodology for the synthesis of electrophoretically DOX-loaded red blood cells (RBC-DOX), as well as the assessment of its antitumorigenic effects in human colon cancer cells (HT-29), and in colon cancer xenograft models...
December 2019: Drug Delivery
Wei Yang, Bing-Hui Jin, Ya-Jing Chen, Chang Cao, Jia-Zhen Zhu, Ying-Zheng Zhao, Xi-Chong Yu, Fan-Zhu Li
Our previous work indicates the lymphatic network and perivascular spaces or tissues might be involved in the facial intradermal brain-targeted delivery of Evans blue (EB). In this article, we presented the detailed involvement of both, and the linkage between lymphatic network and perivascular spaces or tissues. The in-vivo imaging, the trigeminal transection and immunohistochemistry were used. In-vivo imaging indicated intradermal injection in the mystacial pad (i.d.) delivered EB into the brain at 2-, 6- and 24 h, while intranasal injection (i...
December 2019: Drug Delivery
Livia P Mendes, Can Sarisozen, Ed Luther, Jiayi Pan, Vladimir P Torchilin
Modification of nanoparticle surfaces with PEG has been widely considered the gold standard for many years. However, PEGylation presents controversial and serious challenges including lack of functionality, hindered cellular interaction, allergic reactions, and stimulation of IgM production after repetitive dosing that accelerates blood clearance of the nanoparticles. We report the development of novel liposomal formulations surface-modified with a low molecular weight, branched polyethyleneimine (bPEI)-lipid conjugate for use as an alternative to PEG...
December 2019: Drug Delivery
Haonan Dong, Long Pang, Hailin Cong, Youqing Shen, Bing Yu
Nanoparticles have been developed for tumor treatment due to the enhanced permeability and retention effects. However, lack of specific cancer cells selectivity results in low delivery efficiency and undesired side effects. In that case, the stimuli-responsive nanoparticles system designed for the specific structure and physicochemical properties of tumors have attracted more and more attention of researchers. Esterase-responsive nanoparticle system is widely used due to the overexpressed esterase in tumor cells...
December 2019: Drug Delivery
Margo Steuperaert, Charlotte Debbaut, Charlotte Carlier, Olivier De Wever, Benedicte Descamps, Christian Vanhove, Wim Ceelen, Patrick Segers
Although intraperitoneal chemotherapy (IPC) has evolved into an established treatment modality for patients with peritoneal metastasis (PM), drug penetration into tumor nodules remains limited. Drug transport during IPC is a complex process that depends on a large number of different parameters (e.g. drug, dose, tumor size, tumor pressure, tumor vascularization). Mathematical modeling allows for a better understanding of the processes that underlie drug transport and the relative importance of the parameters influencing it...
December 2019: Drug Delivery
Jun Zeng, Chen Li, Xing Duan, Fuyue Liu, Anqin Li, Chunhan Luo, Li Jia, Yifang Gan, Lu Yan, Yaxin Zheng
The lipophilic prodrug of hydrophobic drugs with well-designed molecular structures can form stable pure prodrug nanoparticles (NPs), but rapid NPs aggregation in plasma greatly restricted their direct use for intravenous chemotherapy. To address this, DSPE-mPEG2000 and Cremophor EL are two of the most widely used lipophilic PEG derivatives to enhance their colloidal stability in plasma. However, their drug delivery performances have never been comparatively studied. Here, a redox-responsive lipophilic prodrug of SN38 was chosen as the model drug for such comparative investigations...
December 2019: Drug Delivery
Xiang Yu, Wei Zhou, Hongmei Wang, Sheng Lu, Yiguang Jin, Junhui Fu
Metformin hydrochloride (Met) is commonly used for antidiabetic therapy though its antimelanoma action is also reported. Conventional oral administration method of Met is not appropriate for therapy of melanoma because of large dose, adverse reactions, and low efficiency. Here, a transdermal Met-loaded cubic phase was developed for local treatment of melanoma. In silico formulation optimization of the cubic phases was done, and the corresponding formulations were prepared and characterized. The optimized formulations were screened based on the stable microstructure and proper fluidity...
December 2019: Drug Delivery
Bart J F van den Bemt, Lynda Gettings, Barbara Domańska, Richard Bruggraber, Irina Mountian, Lars E Kristensen
Biologic drugs (e.g. anti-tumor necrosis factors) are effective treatments for multiple chronic inflammatory diseases including rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis. Administration of biologic drugs is usually via subcutaneous self-injection, which provides many patient benefits compared to infusions including increased flexibility, reduced costs, and reduced caregiver burden. However, it is also associated with challenges such as needle phobia, patient treatment misconceptions and incorrect drug administration, and can be impacted by dexterity problems...
December 2019: Drug Delivery
Ningning Song, Lingzhou Zhao, Meilin Zhu, Jinhua Zhao
The identification of markers expressed by pathological cells or their microenvironment would help to distinguish such cells from the normal tissues. The strategies derived from this theory can be a promising modality for imaging and treating diseases. LyP-1, a tumor homing peptide, can selectively bind to its receptor p32 protein overexpressed in various tumor-associated cells and atherosclerotic plaque macrophages. During recent decades, multiple types of LyP-1-based imaging probes and drug delivery systems have been designed and developed for diagnostic and therapeutic applications...
December 2019: Drug Delivery
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Efficient cellular delivery of biologically active molecules is one of the key factors that affect the discovery and development of novel drugs. The plasma membrane is the first barrier that prevents direct translocation of chemic entities, and thus obstructs their efficient intracellular delivery. Generally, hydrophilic small molecule drugs are poor permeability that reduce bioavailability and thus limit the clinic application. The cellular uptake of macromolecules and drug carriers is very inefficient without external assistance...
December 2019: Drug Delivery
Asitha Balachandra, Elsa C Chan, Joseph P Paul, Sze Ng, Vicki Chrysostomou, Steven Ngo, Roshan Mayadunne, Peter van Wijngaarden
Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept...
December 2019: Drug Delivery
Ionut Cristian Radu, Ariana Hudita, Catalin Zaharia, Bianca Galateanu, Horia Iovu, Eugenia Vasile Tanasa, Sabina Georgiana Nitu, Octav Ginghina, Carolina Negrei, Aristidis Tsatsakis, Kelly Velonia, Mikhail Shtilman, Marieta Costache
Aiming to address the issue of poor bioavailability of most anti-tumor medicines against colorectal cancer, we developed a targeted anticancer nanocarrier using biocarriers able to both bind and easily release their load in a controlled manner. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers were obtained via the emulsification-diffusion method, loaded with 5-fluorouracil and then characterized in terms of particle morphology and size (SEM, DLS), drug uptake and release. The cytotoxic potential of the 5-fluorouracil-loaded polymer nanocarriers on human adenocarcinoma cells (HT-29 cell line) was investigated...
December 2019: Drug Delivery
Lili Ren, Jingjing Wang, Guoguang Chen
Glaucocalyxin A (GLA), is a diterpenoid extracted from Hara and has been studied for decades for its diverse bioactivities. However, GLA presents poor solubility in water and low bioavailability through oral administration which has hindered its application in the clinic. So in this study, we prepared the inclusion complex of GLA in SBE-β-CD by ultrasound method and evaluated its antitumor effect and cytotoxic effect on cancer cells. The production of GLA-SBE-β-CD inclusion complex was optimized using Box-Behnken design...
December 2019: Drug Delivery
Qianni Wu, Dong Liu, Xulin Zhang, Dongni Wang, Meimei DongYe, Wan Chen, Duoru Lin, Fangming Zhu, Weirong Chen, Haotian Lin
Tacrolimus has been widely applied to prevent organ rejection after transplantation. However, the conventional pharmaceutical formulation of tacrolimus limits its applications in ocular therapy due to its hydrophobicity and low corneal penetrability. We optimized tacrolimus-loaded methoxy poly (ethylene glycol-block-poly (d, l)-lactic-co-glycolic acid) nanoparticles (TAC-NPs) by simple and effective nanotechnology as a drug delivery system for corneal graft rejection to overcome these drawbacks. The prepared TAC-NPs were 82...
December 2019: Drug Delivery
Leran Bu, Hena Zhang, Kang Xu, Baixiang Du, Caihong Zhu, Yuling Li
We describe a biodegradable amphiphilic polyurethane (PU) with disulfide bonds in the main chain [PEtOz-b-PU(SS)-b-PEtOz]. This multi-block PU was synthesized using poly (ε-caprolactone) diol (PCL-SS-PCL) and poly (2-ethyl-2-oxazoline) (PEtOz-OH) as soft segments, and bis (2-isocyanatoethyl) disulfide as the hard segment. Acid-sensitive PEtOz-OH was used as a hydrophilic segment for pH sensitivity. And reduction sensitivity was induced via disulfide bonds incorporated into the hydrophobic poly (ε-caprolactone) segment of the amphiphilic PUs...
December 2019: Drug Delivery
Chiara Bianca Maria Platania, Michele Dei Cas, Simona Cianciolo, Annamaria Fidilio, Francesca Lazzara, Rita Paroni, Rosario Pignatello, Enrica Strettoi, Riccardo Ghidoni, Filippo Drago, Claudio Bucolo
Myriocin is an antibiotic derived from Mycelia sterilia, and is a potent inhibitor of serine palmitoyltransferase, the enzyme involved in the first step of sphingosine synthesis. Myriocin, inhibiting ceramide synthesis, has a great potential for treatment of diseases characterized by high ceramide levels in affected tissues, such as retinitis pigmentosa (RP). Drug delivery to the retina is a challenging task, which is generally by-passed through intravitreal injection, that represents a risky invasive procedure...
December 2019: Drug Delivery
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