An amphipathic cell penetrating peptide aids cell penetration of cyclosporin A and increases its therapeutic effect in an in vivo mouse model for dry eye disease

2019 ◽  
Vol 55 (91) ◽  
pp. 13657-13660
Author(s):  
Soonsil Hyun ◽  
Lan Li ◽  
Kyung Chul Yoon ◽  
Jaehoon Yu

The use of CPP, LK-3, increases the cell penetration of cyclosporine A (CsA) at nanomolar concentrations and therapeutic efficacy.

2017 ◽  
Vol 58 (3) ◽  
pp. 1682 ◽  
Author(s):  
Hyesook Lee ◽  
Whuisu Shim ◽  
Chae Eun Kim ◽  
So Yeon Choi ◽  
Haeshin Lee ◽  
...  

2012 ◽  
Vol 80 (3) ◽  
pp. 544-552 ◽  
Author(s):  
M. Rodriguez-Aller ◽  
B. Kaufmann ◽  
D. Guillarme ◽  
C. Stella ◽  
P. Furrer ◽  
...  

2021 ◽  
Vol 22 ◽  
Author(s):  
Jizong Jiang

Abstract: Vaccination with small antigens, such as proteins, peptides, or nucleic acids, is used to activate the immune system and trigger the protective immune responses against a pathogen. Currently, nanovaccines are undergoing development instead of conventional vaccines. The size of nanovaccines is in the range of 10–500 nm, which enables them to be readily taken up by cells and exhibit improved safety profiles. However, low-level immune responses, as the removal of redundant pathogens, trigger counter-effective activation of the immune system invalidly and present a challenging obstacle to antigen recognition and its uptake via antigen-presenting cells (APCs). In addition, toxicity can be substantial. To overcome these problems, a variety of cell-penetrating peptide (CPP)-mediated vaccine delivery systems based on nanotechnology have been proposed, most of which are designed to improve the stability of antigens in vivo and their delivery into immune cells. CPPs are particularly attractive components of antigen delivery. Thus, the unique translocation property of CPPs ensures that they remain an attractive carrier with the capacity to deliver cargo in an efficient manner for the application of drugs, gene transfer, protein, and DNA/RNA vaccination delivery. CPP-mediated nanovaccines can enhance antigen uptake, processing, and presentation by APCs, which are the fundamental steps in initiating an immune response. This review describes the different types of CPP-based nanovaccines delivery strategies.


2021 ◽  
Vol 37 (1) ◽  
pp. 4-11
Author(s):  
Jeongah Shin ◽  
Chang Rae Rho ◽  
Joon Young Hyon ◽  
Tae-Young Chung ◽  
Kyung Chul Yoon ◽  
...  

2019 ◽  
Vol 17 ◽  
pp. 891-906 ◽  
Author(s):  
Davide Schiroli ◽  
María J. Gómara ◽  
Eleonora Maurizi ◽  
Sarah D. Atkinson ◽  
Laura Mairs ◽  
...  

2015 ◽  
Vol 56 (12) ◽  
pp. 7179 ◽  
Author(s):  
Ahmad Kheirkhah ◽  
Raheleh Rahimi Darabad ◽  
Andrea Cruzat ◽  
Amir Reza Hajrasouliha ◽  
Deborah Witkin ◽  
...  

2017 ◽  
Vol 27 (6) ◽  
pp. 678-685 ◽  
Author(s):  
Christophe Baudouin ◽  
Maite Sainz de la Maza ◽  
Mourad Amrane ◽  
Jean-Sébastien Garrigue ◽  
Dahlia Ismail ◽  
...  

Purpose The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE). Methods In this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups). Results A total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (≥2 CFS points, ≥30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA. Conclusions In this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.


2017 ◽  
Vol 27 (6) ◽  
pp. e194-e195
Author(s):  
Andrea Leonardi ◽  
Gysbert Van Setten ◽  
Mourad Amrane ◽  
Dahlia Ismail ◽  
Jean-Sebastien Garrigue ◽  
...  

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