Special Issue "Prodrugs"


A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 January 2014)

Special Issue Editors

Guest Editor
Prof. Dr. Jarkko Rautio
School of Pharmacy Faculty of Health Sciences University of Eastern Finland P.O.Box 1627 FI-70211 Kuopio Finland
Website: http://www.uef.fi/en/farmasian-laitos/prodrug-technology
E-Mail: jarkko.t.rautio@uef.fi
Phone: +358 040 3532791
Interests: prodrugs; CNS drug delivery; drug transporters

Co-Guest Editor
Dr. Kristiina Huttunen
School of Pharmacy Faculty of Health Sciences University of Eastern Finland P.O.Box 1627 FI-70211 Kuopio, Finland
E-Mail: Kristiina.huttunen@uef.fi
Interests: design and discovery of prodrugs; perforin inhibitors

Special Issue Information

Dear Colleagues,

We would like to invite you to submit an original manuscript, communication or review for this special issue. Your contribution to this topic will greatly enhance the understanding of this important topic to the readers of Pharmaceuticals. We would like the focus of this issue to be on the structure-activity relationships between promoiety structure and absorption, targeting and/or activation. Additional focus on the physicochemical changes that the prodrug moiety adds to the molecule and how that results in different PK, distribution kinetics and toxicities are also welcome.

Prof. Dr. Jarkko Rautio
Guest Editor


Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).


  • prodrugs
  • bioprecursor
  • bioconversion

Published Papers (2 papers)

Pharmaceuticals 2014, 7(2), 207-219; doi:10.3390/ph7020207
Received: 20 January 2014; in revised form: 8 February 2014 / Accepted: 12 February 2014 / Published: 24 February 2014
Show/Hide Abstract | Download PDF Full-text (128 KB) | View HTML Full-text | Download XML Full-text

Pharmaceuticals 2014, 7(2), 169-191; doi:10.3390/ph7020169
Received: 26 November 2013; in revised form: 15 January 2014 / Accepted: 22 January 2014 / Published: 27 January 2014
Show/Hide Abstract | Download PDF Full-text (514 KB) | View HTML Full-text | Download XML Full-text |  Supplementary Files

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Article
Amino Acid Prodrugs: An Approach to Improve Oral Absorption of Protease Inhibitor, Lopinavir
Authors: Mitesh Patel, Nanda K. Mandava and Ashim K. Mitra*.
: University of Missouri Curators’ Professor of Pharmacy, Chair, Division of Pharmaceutical Sciences, Vice-Provost for Interdisciplinary Research, University of Missouri - Kansas City. Phone: +816-235-1615. Fax: +816-235-5779. Email: mitraa@umkc.edu
Introduction: Efflux proteins such as poly-glycoprotein (P-gp) and multidrug resistance associated proteins (MRPs) are one of the major causes for drug resistance. Lopinavir (LPV) is a protease inhibitors (PIs) indicated in HAART for the treatment of HIV infection. Inclusion of PIs in HAART has significantly improved clinical outcomes in HIV infected patients. However, the major problem associated with present anti-HIV drug regimen is inability of PIs to attain sufficient therapeutic concentrations inside the brain. Presence of P-gp and MRPs on the luminal side of brain capillary endothelial cells has been the major factor limiting permeation of PIs into the brain. Thus, circumvention of these proteins might be helpful in improving drug efficacy. Methods: In this study, amino acid prodrugs of LPV were investigated for their potential in evading efflux proteins. Three amino acid prodrugs were synthesized by conjugating isoleucine, tryptophan and methionine to LPV. Prodrugs were identified by NMR and LCMS/MS analysis. The interaction of LPV prodrugs were performed in P-gp and MRP2 overexpressing cells (MDCK-MDR1, MDCK-MRP2). Oral absorption in Male Sprague Dawley Rats was performed to investigate the effect of amino acid derivatization in improving oral LPV bioavailability Results: Distinct peaks were obtained at 742, 760 and 814 in LCMS/MS analysis for isoleucine, methionine and tryptophan LPV prodrugs. Solubility of prodrugs was significantly higher compared to LPV. Prodrugs were very stable at acidic pH and degraded rapidly at basic pH. [3H]-LPV uptake markedly increased in presence of GF 120918 and MK 571, indicating that LPV has high affinity towards P-gp and MRP-2. Uptake of [3H]-LPV remained unaltered in presence of prodrugs suggesting that prodrugs exhibited reduced affinity towards P-gp and MRP2. Transepithelial transport of prodrugs was higher than LPV in MDCK-MDR1 and MDCK-MRP2 cells, suggesting that absorption of prodrugs might be greater than LPV. Oral absorption studies demonstrated higher AUC for prodrugs relative to LPV following oral administration. Conclusion: This study demonstrated that amino acid prodrugs could be a viable approach for enhancing intestinal absorption of LPV. Such strategy could be useful in enhancing brain permeability of LPV as BBB highly expresses P-gp and MRPs on the apical side of brain endothelial cells.

Last update: 27 February 2014

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