scholarly journals Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1960
Author(s):  
Harold W. Davis ◽  
Subrahmanya D. Vallabhapurapu ◽  
Zhengtao Chu ◽  
Michael A. Wyder ◽  
Kenneth D. Greis ◽  
...  

Glioblastoma multiforme (GBM), a common type of brain cancer, has a very poor prognosis. In general, viable GBM cells exhibit elevated phosphatidylserine (PS) on their membrane surface compared to healthy cells. We have developed a drug, saposin C-dioleoylphosphatidylserine (SapC-DOPS), that selectively targets cancer cells by honing in on this surface PS. To examine whether SapC-DOPS, a stable, blood–brain barrier-penetrable nanovesicle, could be an effective delivery system for precise targeted therapy of radiation, we iodinated several carbocyanine-based fluorescent reporters with either stable iodine (127I) or radioactive isotopes (125I and 131I). While all of the compounds, when incorporated into the SapC-DOPS delivery system, were taken up by human GBM cell lines, we chose the two that best accumulated in the cells (DiI (22,3) and DiD (16,16)). Pharmacokinetics were conducted with 125I-labeled compounds and indicated that DiI (22,3)-SapC-DOPS had a time to peak in the blood of 0.66 h and an elimination half-life of 8.4 h. These values were 4 h and 11.5 h, respectively, for DiD (16,16)-SapC-DOPS. Adult nude mice with GBM cells implanted in their brains were treated with 131I-DID (16,16)-SapC-DOPS. Mice receiving the radionuclide survived nearly 50% longer than the control groups. These data suggest a potential novel, personalized treatment for a devastating brain disease.

Author(s):  
Eva Medina ◽  
Carlos A. Guzmán ◽  
Lothar H. Staendner ◽  
Mario P. Colombo ◽  
Paola Paglia

Author(s):  
Amit Prakash ◽  
Amit Prakash

Oral drug delivery is the most commonly used and preferred route of delivery of pharmaceuticals which has been successfully treating wide number of diseases. The advantages of this method of delivery are patient friendly, cost effective, established delivery system, noninvasiveness and convenient, and In the pharmaceutical field it is the most favored drug delivery system. Oral drug delivery systems along with other effective delivery system types that are effective and promising are discussed in this paper based on the mechanism of drug release.


2009 ◽  
Vol 26 (6) ◽  
pp. 1477-1485 ◽  
Author(s):  
Barbara C. Baudner ◽  
Vanessa Ronconi ◽  
Daniele Casini ◽  
Marco Tortoli ◽  
Jina Kazzaz ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6972 ◽  
Author(s):  
Monika Naumowicz ◽  
Magdalena Kusaczuk ◽  
Marcin Zając ◽  
Miroslav Gál ◽  
Joanna Kotyńska

Cinnamic acid (CA) and ferulic acid (FA) are naturally occurring phenolic acids claimed to exert beneficial effects against disorders related to oxidative stress, including cancer. One such malignancy that still remains a therapeutic challenge mainly due to its heterogeneity and inaccessibility to therapeutic agents is Glioblastoma multiforme (GBM). Here, the influence of CA and FA on the surface charge density of human GBM cell line LN-229 was studied using the electrophoretic light scattering technique. Also, the cytotoxicity of both phenolic acids was determined by metabolic activity-assessing tetrazolium test (MTT) analysis after exposure to CA and FA for 24 h and 48 h. Results showed that both compounds reduced cell viability of LN-229 cells, with more pronounced effect evoked by CA as reflected in IC50 values. Further analyses demonstrated that, after treatment with both phenolic acids, the negative charge of membranes decreased at high pH values and the positive charge of the membranes increased at low pH values compared to the data obtained for untreated cells. Afterward, a four-equilibrium model was applied to estimate the total surface concentrations of both acidic and basic functional groups and their association constants with solution ions in order to calculate theoretical values of membrane surface charge densities. Then, the theoretical data were compared to the experimental data in order to verify the mathematical model. As such, our results indicate that application of electrochemical methods to determine specific drug–membrane interactions might be crucial for predicting their pharmacological activity and bioavailability.


1982 ◽  
Vol 53 (5) ◽  
pp. 1263-1272 ◽  
Author(s):  
G. A. Farkas ◽  
C. Roussos

In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.


2019 ◽  
Vol 51 ◽  
pp. 290-296 ◽  
Author(s):  
Sepehr Soleymani ◽  
Fatemeh Yari ◽  
Azam Bolhassani ◽  
Haleh Bakhshandeh

2020 ◽  
Vol 21 (22) ◽  
pp. 8846
Author(s):  
Giuseppe Pepe ◽  
Enrica Calce ◽  
Valentina Verdoliva ◽  
Michele Saviano ◽  
Vittorio Maglione ◽  
...  

Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington’s disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood–brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability. The prepared hyaluronan-based materials able to self-assemble in stable spherical nanoparticles, consist of natural fatty acids chemically conjugated to the natural polysaccharide. The aim of this study is to provide a possible effective delivery system for curcumin with the expectation that, after having released the drug at the specific site, the biopolymer can degrade to nontoxic fragments before renal excretion, since all the starting materials are provided by natural resource. Our findings demonstrate that curcumin-encapsulated nanoparticles enter the cells and reduce their susceptibility to apoptosis in an in vitro model of Huntington’s disease.


2016 ◽  
Vol 45 (2) ◽  
pp. 291-296 ◽  
Author(s):  
Yousef Amini ◽  
Majid Tebianian ◽  
Nader Mosavari ◽  
Mahdi Fasihi Ramandi ◽  
Seyyd Mahmoud Ebrahimi ◽  
...  

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