Pharmacokinetic Properties of Cytokines in Their Targeted Delivery Based on Autologous Erythrocyte Pharmacocytes
##plugins.themes.bootstrap3.article.main##
Аннотация
Introduction. Using autologous erythrocytes as drug carriers for targeted delivery of cytokines to the sites of inflammation could potentially provide new opportunities for treatment of patients with purulent diseases. The targeted characteristic of erythrocytes is associated with the nature of purulent inflammation, where a large amount of erythrocytes is phagocytized and drugs encapsulated into the erythrocytes could be easily released. On the other hand, autologous erythrocytes meet all the criteria for the ideal drug carrier. They are nontoxic, not immunogenic, and able to bear a large number of drug molecules while preserving an original conformation of the drugs. Thus, in this study, we aimed to analyze pharmacokinetic profiles of IL-1? encapsulated into erythrocytes’ ghosts (pharmacocytes) in comparison to intravenously injected free IL-1?.
Material and methods. Albino rats were randomly divided into two groups, each group receiving a different kind of IV injection via the tail vein. Group A (control) received 500 µg of free IL-1?, and group B received an injection of 1 ml of pharmacocytes loaded with 500 µg of test substance. At fixed time points after injection (15, 30, 60, 180, 540, 720, and 1,440 minutes) serum samples were collected. Homogenates of liver, spleen, lung, heart, kidney, and adipose tissue were obtained 24 hours after injections. Concentration of the tested substance in the collected organs and blood plasma were measured by ELISA.
Results. We have observed an increased half-life period (T1/2) for encapsulated IL-1? compared to the control. T1/2 for free IL-1? was one hour, while administration of loaded pharmacocytes allowed the half-life period to increase by more than 15 fold (1,043.40 ± 137.92 min) preserving high level of IL-1? activity in the blood samples up to 24 hours. The increased time of IL-1? presence in the body when administered in the form of pharmacocytes could be explained by reduction of elimination constant (Cel) by 1.6 fold, and clearance (CLel) by more than 100 fold. We also observed an increased concentration of IL-1? in liver, spleen, and lung over at least 24 hours. When administered in free form, IL-1? disappeared from these organs within 6 hours.
Conclusions. Pharmacocytes have shown to improve pharmacokinetic profiles of IL-1? by increasing the half-life period of the cytokine, reducing its clearance and elimination as well as increasing the deposition of the drug in liver, spleen and lungs. These data suggest that pharmacocytes be effective drug carriers for targeted delivery of cytokines to the sites of inflammation and have a potential for improving the treatment outcomes of purulent diseases.
##plugins.themes.bootstrap3.article.details##
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site;
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Revised 7/16/2018. Revision Description: Removed outdated link.