scholarly journals Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells

2019 ◽  
Vol 22 ◽  
pp. 191-220 ◽  
Author(s):  
Maryam Saadat ◽  
Fahimeh Zahednezhad ◽  
Parvin Zakeri-Milani ◽  
Hamid Reza Heidari ◽  
Javid Shahbazi-Mojarrad ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Targeting ◽  
Blood Circulation ◽  
Positive Charge ◽  
Nano Particles ◽  
Proton Sponge ◽  
Passive Targeting ◽  
P Glycoprotein ◽  
Positively Charged

The aim of this review was to describe the preferred charged nano-particles (CNPs) for targeted delivery in tumor cells. Zeta Potential (ZP), which represents the surface charge of NPs was highlighted in cell entrance and interactions. In this regard, various types of endocytosis pathways which are involved in NPs’ uptake were first introduced. Then, significance of positively charged NPs (PCNPs) in proton sponge effect corresponding to lysosomal escape was discussed. Cells prefer to endocyte the NPs with positive charge in passive targeting and gene delivery, while in active targeting; the charge of receptors’ ligand binding site determines the NPs cellular uptake. Moreover, pH-sensitive NPs represent charge reversible behavior depending on pH changes which leads to longer blood circulation residence and higher uptake at acidic microenvironment of the cancer media. Role of the CNPs in overcoming multidrug resistance (MDR) and bypassing p-glycoprotein was further investigated.

Role of S4 positively charged residues in the regulation of Kv4.3 inactivation and recovery

2007 ◽  
Vol 293 (3) ◽  
pp. C906-C914 ◽  
Author(s):  
Matthew R. Skerritt ◽  
Donald L. Campbell
Keyword(s):  
Positive Charge ◽  
Voltage Sensitivity ◽  
Shaker Channels ◽  
Recovery From Inactivation ◽  
Kv4 Channels ◽  
Charged Residues ◽  
Arginine Residues ◽  
Voltage Sensing Domain ◽  
Positively Charged

The molecular and biophysical mechanisms by which voltage-sensitive K+ (Kv)4 channels inactivate and recover from inactivation are presently unresolved. There is a general consensus, however, that Shaker-like N- and P/C-type mechanisms are likely not involved. Kv4 channels also display prominent inactivation from preactivated closed states [closed-state inactivation (CSI)], a process that appears to be absent in Shaker channels. As in Shaker channels, voltage sensitivity in Kv4 channels is thought to be conferred by positively charged residues localized to the fourth transmembrane segment (S4) of the voltage-sensing domain. To investigate the role of S4 positive charge in Kv4.3 gating transitions, we analyzed the effects of charge elimination at each positively charged arginine (R) residue by mutation to the uncharged residue alanine (A). We first demonstrated that R290A, R293A, R296A, and R302A mutants each alter basic activation characteristics consistent with positive charge removal. We then found strong evidence that recovery from inactivation is coupled to deactivation, showed that the precise location of the arginine residues within S4 plays an important role in the degree of development of CSI and recovery from CSI, and demonstrated that the development of CSI can be sequentially uncoupled from activation by R296A, specifically. Taken together, these results extend our current understanding of Kv4.3 gating transitions.

scholarly journals Nanocarriers for Diagnosis and Targeting of Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Arun Sharma ◽  
Nitin Jain ◽  
Rashmi Sareen
Keyword(s):  
Breast Cancer ◽  
Blood Circulation ◽  
Tumor Targeting ◽  
Cytotoxic Effect ◽  
Imaging Diagnosis ◽  
Passive Targeting ◽  
Specific Tumor ◽  
Polymeric Drug ◽  
Cancer Cell Targeting

Breast cancer nanotherapeutics is consistently progressing and being used to remove the various limitations of conventional method available for the diagnosis and treatment of breast cancer. Nanoparticles provide an interdisciplinary area for research in imaging, diagnosis, and targeting of breast cancer. With advanced physicochemical properties and better bioavailability, they show prolonged blood circulation with efficient tumor targeting. Passive targeting mechanisms by using leaky vasculature, tumor microenvironment, or direct local application and active targeting approaches using receptor antibody, amplification in the ability of nanoparticles to target specific tumor can be achieved. Nanoparticles are able to reduce cytotoxic effect of the active anticancer drugs by increasing cancer cell targeting in comparison to conventional formulations. Various nanoparticles-based formulations are in the preclinical and clinical stages of development; among them, polymeric drug micelles, liposomes, dendrimer, carbon nanotubes, and nanorods are the most common. In this review, we have discussed the role of nanoparticles with respect to oncology, by particularly focusing on the breast cancer and various nanodelivery systems used for targeting action.

scholarly journals A positive charge region of Salmonella FliI is required for ATPase formation and efficient flagellar protein export

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Miki Kinoshita ◽  
Keiichi Namba ◽  
Tohru Minamino
Keyword(s):  
Positive Charge ◽  
Protein Export ◽  
Active Protein ◽  
Gain Of Function ◽  
Charged Cluster ◽  
Charge Cluster ◽  
Flagellar Assembly ◽  
Flagellar Protein ◽  
Positively Charged

AbstractThe FliH2FliI complex is thought to pilot flagellar subunit proteins from the cytoplasm to the transmembrane export gate complex for flagellar assembly in Salmonella enterica. FliI also forms a homo-hexamer to hydrolyze ATP, thereby activating the export gate complex to become an active protein transporter. However, it remains unknown how this activation occurs. Here we report the role of a positively charged cluster formed by Arg-26, Arg-27, Arg-33, Arg-76 and Arg-93 of FliI in flagellar protein export. We show that Arg-33 and Arg-76 are involved in FliI ring formation and that the fliI(R26A/R27A/R33A/R76A/R93A) mutant requires the presence of FliH to fully exert its export function. We observed that gain-of-function mutations in FlhB increased the probability of substrate entry into the export gate complex, thereby restoring the export function of the ∆fliH fliI(R26A/R27A/R33A/R76A/R93A) mutant. We suggest that the positive charge cluster of FliI is responsible not only for well-regulated hexamer assembly but also for substrate entry into the gate complex.

Pharmacogenetics of Clozapine: In Vivo Role of Cytochrome P450 Isoforms and P-Glycoprotein

2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap
Keyword(s):  
Cytochrome P450 ◽  
P Glycoprotein ◽  
Cytochrome P450 Isoforms

The neuroendocrinological role of P-glycoprotein

2005 ◽  
Vol 113 (08) ◽  
Author(s):  
M Ebinger ◽  
MB Müller ◽  
M Uhr
Keyword(s):  
P Glycoprotein

Anticancer Nano Formulation of Imatinib with Chitosan Polymer

2019 ◽  
Vol 9 (01) ◽  
pp. 58-64
Author(s):  
Senthilnathan B ◽  
Billy Graham R ◽  
Chaarmila Sherin C ◽  
Vivekanandan K ◽  
Bhavya E
Keyword(s):  
Drug Release ◽  
Drug Targeting ◽  
Bone Marrow Failure ◽  
Lymphoblastic Leukemia ◽  
Release Profile ◽  
Nano Particles ◽  
Drug Release Profile ◽  
Study Results ◽  
Mast Cell Disease ◽  
Nano Formulation

Objective: Drug targeting is the capacity of the dosage form. In which the therapeutic agent acts specifically to desired site of action in the non-targeted tissue with the help of Nano particles is called as the drug targeting. IMATINIB is a used to treat cancer by chemo therapy. Cancers like chronic myeloid leukemia cancer (CML) and acute lymphoblastic leukemia cancer (ALL) and other specific types of gastrointestinal stromal cell tumor (GIST) systemic mast cell disease and Bone marrow failure disorder. It is administered by oral root. For ATP, Tyrosine kinase is act as a binding site. Methodology: The drug IMATINIB is loaded in the polymer chitosan, poly-(D) glucosamine is a bio compactible, bio degradable, nontoxic, antimicrobial and soluble in solvents. This preparation is done by emulsion-droplet coalescence method. Content of the Drug, Size of the particle and Zeta potential, Encapsulation efficiency and Drug release testing are described for this formulation in this study. Results: The Imatinib Nano particles were formulated and evaluated for its invitro drug release profile. Based on the invitro drug release profile of Imatinib nano particles formulation (INP1 – INP5) formulation INP3 was selected as the best formulation in which the particle size was 285.9nm. The invitro % drug release of INP3 formulation was 99.76 ± 0.82 and it was found to be the suitable formulation to manage the cancer. Conclusion: Hence it is concluded that the newly formulated controlled release nanoparticle drug delivery system of Imatinib may be idol and effective by allowing the drug to release continuously for 24 hrs.

Hypothetical Role of Growth Factors to Reduce Intervertebral Disc Degeneration Significantly through Trained Biological Transformations

2020 ◽  
Vol 26 ◽  
Author(s):  
Cristian Muresanu ◽  
Siva G. Somasundaram ◽  
Sergey V. Vissarionov ◽  
Liliya V. Gavryushova ◽  
Vladimir N. Nikolenko ◽  
...  
Keyword(s):  
Growth Factors ◽  
Blood Circulation ◽  
Seminal Fluid ◽  
Prostate Gland ◽  
The Body ◽  
Personal Experiences ◽  
Biological Transformation ◽  
The Mind

Background: From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. Objective: We seek to stimulate discussions and more research about the possibility of using the already available growth factors found in the prostate gland and endometrium by starting a novel educable physiology, known as biological transformations controlled by the mind. Methods: We summarized the stretch-gated ion channel mechanism of the cell membrane, and offer several practical methods that can be applied by anyone, in order to stimulate and enhance the blood circulation of the growth factors from the seminal fluid to sites throughout the body. This details the practical application of our earlier published studies about biological transformations. Results: A previously reported single-patient case study has been extended, adding more from his personal experiences continually improving this novel physiological training and extending the ideas from our earlier findings in detail. Conclusion: The biological transformation findings demonstrate the need additional research to establish the benefits of these natural therapies to repair and rejuvenate tissues affected by various chronic diseases or aging processes.

Role of novel drug delivery systems in coronavirus disease-2019 (covid-19): time to act now

2020 ◽  
Vol 17 ◽  
Author(s):  
Neeraj Mittal ◽  
Varun Garg ◽  
Sanjay Kumar Bhadada ◽  
O. P. Katare
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
World Health ◽  
Ongoing Research ◽  
Standard Drug ◽  
Corona Virus ◽  
Novel Drug

: The corona virus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel corona virus SARS-CoV2, previously named as 2019-nCoV. COVID-19 has spread across the globe and declared as pandemic by World health organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, so repurposing of existing drugs is the only solution. Novel drug delivery systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for treatment of various viral diseases and their relevance in COVID-19 has discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for a potential targeted delivery. So in these tough times, NDDS and nanotechnology can be a safeguard to humanity.

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