Delivery Strategies to Improve In Vivo Stability of Immunogenic Peptide PADRE

Order of Publishing in Issue: 
3
Volume :6
Issue :2
April, 2012
Page No: 
166-172
Authors: 
Srinivas Poondru[1,2], Vivek Purohit[1], Poonam Saraf[1] and Bhaskara Jasti [1]
Address: 
[1] Thomas J. Long School of Pharmacy & Health Sciences, University of the Paciûc, 3601 Paciûc Avenue, Stockton, CA 95211, United States
Address: 
[2] Current address: OSI Pharmaceuticals, Inc., Deerfield, IL, USA
Email-ID: 
bjasti@pacific.edu

Abstract
PADRE, a peptide with potential in breast cancer immunotherapy exhibits low in vivo efficacy due to poor tumor uptake and significant enzymatic degradation. In the present work, novel delivery based approaches were utilized to improving the efficacy of PADRE. The utility of these approaches in the delivery of PADRE was tested on in vitro cell based models. In the in vitro systems, PADRE was not internalized in Caco-2 cells to a significant extent as observed from the concentrations in cell pellet, which were always lower than 5%. Also, 90% of PADRE externally associated with the Caco-2 cells was degradated within 4 hours, possibly due to the breakdown by ecto-peptidases associated with tumor cells. Enzyme inhibitors, antitrypsin reduced the PADRE degradation in Caco-2 cells (20%) as compared to untreated cells (55%). The lipoprotein based systems were formulated using with and without 0.1% sodium lauryl sulfate that yielded 45 and 53% loading of PADRE, respectively. The efficacy of PADRE lipoproteinbased systems was determined by performing CD4 proliferation assay. The lipoprotein based systems with 20 ìg/mL treatment with and without 0.1% sodium lauryl sulfate showed 3.2 and 2.8 times CD4 proliferation observed as compared to control. The CD4 proliferation on treatment with native PADRE was 4.3 times compared to a no treatment control, however this was not statistically significant (p>0.05) when compared to the PADRE activity from lipoprotein systems indicating that thelipoprotein-based approach was suitable delivering PADRE as it retained the immunogenic activity. The strategies studied to deliver PADRE were successful in vitro and showed potential for improving its immunogenic efficacy in vivo by improving its stability.

Keywords: 
PADRE delivery, peptidase inhibitors, lipoprotein delivery system
AttachmentSize
Paper-3.pdf285.02 KB

 
To download full text articles and issues in PDF at no cost.All you have to do is fill out a brief registration form. It's easy and it's free. At any time, you may request removal of your contact information from our database.
Click here to Register | Click here if you have already registered

2018 ABAP Awards

Invitation for Nominations to 2019 ABAP Awards
The Association of Biotechnology and Pharmacy invites nominations for the following awards from the eligible talented people with proven track record and achievements on or before August 31, 2019 in the prescribed format.

DOWNLOAD CIRCULAR | APPLICATION FORM

AWARDS

User login