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peptide drug delivery

Caslin A Gilroy, Stefan Roberts, Ashutosh Chilkoti
Fibroblast growth factor 21 (FGF21) is under investigation as a type 2 diabetes protein drug, but its efficacy is impeded by rapid in vivo clearance and by costly production methods. To improve the protein's therapeutic utility, we recombinantly expressed FGF21 as a fusion with an elastin-like polypeptide (ELP), a peptide polymer that exhibits reversible thermal phase behavior. Below a critical temperature, ELPs exist as miscible unimers, while above, they associate into a coacervate. The thermal responsiveness of ELPs is retained upon fusion to proteins, which has notable consequences for the production and in vivo delivery of FGF21...
March 15, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Elnaz Bagheri, Legha Ansari, Khalil Abnous, Seyed Mohammad Taghdisi, Fahimeh Charbgoo, Mohammad Ramezani, Mona Alibolandi
Silica hybrid materials play an important role in improvement of novel progressive functional nanomaterials. Study in silica hybrid functional materials is supported by growing interest in providing intelligent materials that combine best of the inorganic silica structure along with organic or biological realms. Hybrid silica materials do not only provide fantastic opportunities for the design of novel materials for research but their represented unique properties open versatile applications specifically in nanomedicine since it was recognized by US FDA as a safe material for human trials...
March 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Dirk van den Brand, Cornelia Veelken, Leon Massuger, Roland Brock
Drug delivery into tumors and metastases is a major challenge in the eradication of cancers such as epithelial ovarian carcinoma. Cationic cell-penetrating peptides (CPPs) are a promising group of delivery vehicles to mediate cellular entry of molecules that otherwise poorly enter cells. However, little is known about their penetration behavior in tissues. Here, we investigated penetration of cationic CPPs in 3D ovarian cancer spheroids and patient-derived 3D tumor explants. Penetration kinetics and distribution after long-term incubation were imaged by confocal microscopy...
March 14, 2018: Biochimica et Biophysica Acta
Niloy Kundu, Debasis Banik, Nilmoni Sarkar
Amphiphiles are class of molecules which are known to assemble into a variety of nanostructures. The understanding and applications of self-assembled systems are based on what has been learned from biology. Among the vast number of self-assemblies, in this article, we have described the formation, characterization and dynamics of two important biologically inspired assemblies, vesicles and fibrils. Vesicles, which can be classified into several categories depending on the sizes and components, are of great interest due to their potential application in drug delivery and as nanoscale reactor...
March 15, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Muyang Yang, Lixia Yu, Ruiwei Guo, Anjie Dong, Cunguo Lin, Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell...
March 15, 2018: Nanomaterials
Kuikun Yang, Yijing Liu, Yi Liu, Qian Zhang, Chuncai Kong, Chenglin Yi, Zijian Zhou, Zhantong Wang, Guofeng Zhang, Yang Zhang, Niveen M Khashab, Xiaoyuan Chen, Zhihong Nie
This article describes the fabrication of nanosized magneto-vesicles (MVs) comprising tunable layers of densely-packed superparamagnetic iron oxide nanoparticles (SPIONs) in membranes via cooperative assembly of polymer-tethered SPIONs and free poly(styrene)-b-poly(acrylic acid) (PS-b-PAA). The membrane thickness of MVs could be well controlled from 9.8 to 93.2 nm by varying the weight ratio of PS-b-PAA to SPIONs. The increase in membrane thickness was accompanied with the transition from monolayer MVs, to double-layered MVs and to multilayered MVs (MuMVs)...
March 15, 2018: Journal of the American Chemical Society
Ming-Xing Zhang, Shan-Shan Hong, Qing-Qing Cai, Meng Zhang, Jun Chen, Xiao-Yan Zhang, Cong-Jian Xu
Ovarian cancer is the leading cause of cancer death among gynecological malignancies. The high mortality rate has not been significantly reduced despite advances in surgery and chemotherapy. Gene therapy shows therapeutic potential, but several key issues must be resolved before clinical application. To minimize toxicity in noncancerous tissues, tumor-specific ligands are conjugated to vectors to increase the selectivity of drug delivery. The expression pattern of follicle-stimulating hormone (FSH) receptor in normal and cancer tissues provides an opportunity for highly selective drug delivery in ovarian cancer...
November 2018: Drug Delivery
Mao Li, Stefanie Mosel, Shirley K Knauer, Carsten Schmuck
Herein, we report a rather simple strategy to enhance the anion binding ability of a dipeptide to achieve cell uptake and also protein delivery. Peptide 1, composed of only two synthetic amino acids with an artificial anion binding site in the side chains, has an overall molecular weight of only 630 Da and demonstrated strong binding affinity (107 M-1 ) and clustering ability with heparin as a model for cell surface sugars. Furthermore, peptide 1 is also efficiently taken up by cells most likely via endocytosis...
March 14, 2018: Organic & Biomolecular Chemistry
Hari R Desu, Laura A Thoma, George C Wood
PURPOSE: Acute lung injury (ALI) is a fatal syndrome in critically ill patients. It is characterized by lung edema and inflammation. Numerous pro-inflammatory mediators are released into alveoli. Among them, interleukin-1beta (IL-1β) causes an increase in solute permeability across the alveolar-capillary barrier leading to edema. It activates key effector cells (alveolar epithelial and endothelial cells) releasing inflammatory chemokines and cytokines. The purpose of the study was to demonstrate that nebulized liposomes inhibit ALI in vivo...
March 13, 2018: Pharmaceutical Research
Shihong Shao, Yun Zhu, Tingting Meng, Yupeng Liu, Yun Hong, Ming Yuan, Hong Yuan, Fuqiang Hu
Liver metastasis is a leading death cause in colorectal cancer. The pathological differences between orthotopic tumors and metastatic lesions increased the therapeutic difficulty of metastasis. Herein, the α5β1 integrin receptor expression on metastatic cells was firstly measured, the result showed that metastatic cells expressed higher α5β1 integrin compared with original cells from orthotopic tumors. Afterwards, RPM peptide modified chitosan-stearic (RPM-CSOSA) was designed based on α5β1 integrin expression...
March 13, 2018: Molecular Pharmaceutics
Shota Ichimizu, Hiroshi Watanabe, Hitoshi Maeda, Keisuke Hamasaki, Yuka Nakamura, Victor Tuan Giam Chuang, Ryo Kinoshita, Kento Nishida, Ryota Tanaka, Yuki Enoki, Yu Ishima, Akihiko Kuniyasu, Yoshihiro Kobashigawa, Hiroshi Morioka, Shiro Futaki, Masaki Otagiri, Toru Maruyama
Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA...
March 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Tsukuru Masuda, Naohiko Shimada, Atsushi Maruyama
Membrane active peptides (MAPs) have potential applications in drug delivery systems and as antimicrobials. We previously showed that a cationic comb-type copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex), forms a soluble inter-polyelectrolyte complex with an anionic MAP, the E5 peptide, resulting in significant enhancement of the membrane disruption activity of E5. In this study, we designed a novel comb-type cationic copolymer composed of a PAA main chain and thermo-responsive poly(N-isopropylacrylamide) graft chains (PAA-g-PNIPAAm)...
March 12, 2018: Biomacromolecules
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
Rui Huang, Jiawei Li, Dereje Kebebe, Yumei Wu, Bing Zhang, Zhidong Liu
Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR)...
November 2018: Drug Delivery
Dipendra Gyawali, Jimin P Kim, Jian Yang
A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability. The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free one-pot reaction, derived entirely from biocompatible monomers citric acid, maleic acid, L-cysteine, and poly(ethylene glycol). The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity, and demonstrate long-term structural stability in biological buffer for two weeks...
March 2018: Bioactive Materials
Moomal Tasneem, Carly Mannix, Annette Wong, Jennifer Zhang, Gopala Rangan
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]...
March 6, 2018: World Journal of Nephrology
Lucía Martínez-Jothar, Sofia Doulkeridou, Raymond M Schiffelers, Javier Sastre Torano, Sabrina Oliveira, Cornelus F van Nostrum, Wim E Hennink
Maleimide-thiol chemistry is widely used for the design and preparation of ligand-decorated drug delivery systems such as poly(lactide-co-glycolide) (PLGA) based nanoparticles (NPs). While many publications on nanocarriers functionalized exploiting this strategy are available in the literature, the conditions at which this reaction takes place vary among publications. This paper presents a comprehensive study on the conjugation of the peptide cRGDfK and the nanobody 11A4 (both containing a free thiol group) to maleimide functionalized PLGA NPs by means of the maleimide-thiol click reaction...
March 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Zachary F Walls, Matthew Schwengels, Victoria Palau
The use of peptides in drug development has been hampered by their poor pharmaceutical properties, most notably their inability to reliably permeate biological membranes and lack of targeting. To overcome these disadvantages, the AMino acid Intracellular Delivery SysTem (AMIDST) was developed. This modular peptide-based delivery system confers cellular permeability and organelle-specific targeting for therapeutic peptides. As demonstrated in this study, the delivery of a HER2-binding peptide to the secretory organelles of breast cancer cells resulted in intracellular sequestration, a reduction in downstream signaling, and reduced viability compared to the delivery of a control peptide...
March 9, 2018: Journal of Drug Targeting
Fangyuan Guo, Dongxue Huang, Wei Zhang, Qinying Yan, Qingliang Yang, Yan Yang, Hanbing Li, Junxian Yun, Weiyong Hong, Gensheng Yang
Elastomers are largely developed for biomedical applications; however, little is reported on them although they are an effective and controllable delivery system for proteins. In the present study, we investigated the pharmacokinetics, biosecurity, and hypoglycemic effect of an insulin-loaded elastomer formulation in diabetic rats. Cylindrical insulin-loaded elastomers were fabricated using a UV cross-linking process based on methyl-acrylic-star-poly(ε-caprolactone-co-D,L-lactide) cyclic ester and methyl-bi-acrylic-poly(ε-caprolactone-b-polyethylene glycol-b-ε-caprolactone) (CLPEGCLMA)...
March 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Zhigao Niu, Eleni Samaridou, Emilie Jaumain, Julie Coëne, Gabriela Ullio, Neha Shrestha, Josep Garcia, Matilde Durán-Lobato, Sulay Tovar, Manuel J Santander-Ortega, M Victoria Lozano, M Mar Arroyo-Jiménez, Rocío Ramos-Membrive, Iván Peñuelas, Aloïse Mabondzo, Véronique Préat, Meritxell Teixidó, Ernest Giralt, María José Alonso
The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer...
March 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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