dc.contributor.author |
Liu, Mengyang |
|
dc.contributor.author |
Svirskis, Darren |
|
dc.contributor.author |
Proft, Thomas |
|
dc.contributor.author |
Loh, Jacelyn |
|
dc.contributor.author |
Chen, Shuo |
|
dc.contributor.author |
Kang, Dali |
|
dc.contributor.author |
Wen, Jingyuan |
|
dc.coverage.spatial |
Netherlands |
|
dc.date.accessioned |
2022-09-15T04:43:40Z |
|
dc.date.available |
2022-09-15T04:43:40Z |
|
dc.date.issued |
2022-08-19 |
|
dc.identifier.citation |
(2022). International Journal of Pharmaceutics, 122123-. |
|
dc.identifier.issn |
0378-5173 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/61251 |
|
dc.description.abstract |
The oral delivery of medicines is the most popular route of administration for patients. However, thymopentin (TP5) is only available in the market in forms for parenteral administration. In large part, this is because of extensive peptidolytic degradation in the gastrointestinal tract (GIT), which decreases the amount of TP5 available for absorption. This study aims to understand the extent of TP5 peptideolysis and determine effective inhibitors and suitable lipid-based nanocarriers to aid in the development of an effective oral delivery formulation. Enzymatic degradation kinetics of TP5 was investigated in the presence or absence of mucosal and luminal components extracted from various parts of the rat intestine, including the duodenum, jejunum, ileum, and colon. Inhibition of TP5 enzymatic peptidolysis was screened in the presence or absence of EDTA, trypsin and chymotrypsin inhibitors from soybean (SBTCI), and bestatin. TP5 with SBTCI was loaded into lipid-based nanocarriers, including microemulsions, niosomes and solid lipid nanoparticles. These TP5-loaded nanocarriers were investigated through characterization of morphology, particle size, zeta potential, entrapment efficacy (EE%), and ex vivo rat intestinal degradation studies to select a lead formulation for a future oral drug delivery study. The degradation kinetics of TP5 followed pseudo-first-order kinetics, and the biological metabolism of TP5 was displayed in the presence of luminal contents, indicating that TP5 is sensitive to luminal enzymes. Notably, a considerable decrease in TP5 peptidolysis was found in the presence of SBTCI, bestatin, and EDTA. TP5 and SBTCI were loaded into three lipid-based delivery systems, displaying superior protection under ex vivo intestinal luminal contents and mucosal homogenates for 6 hours compared with the pure drug solution. These findings suggest that using select inhibitors and lipid-based nanocarriers can decrease peptide degradation and may improve oral bioavailability of TP5 following oral administration. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Elsevier |
|
dc.relation.ispartofseries |
International journal of pharmaceutics |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
Thymopentin (TP5) |
|
dc.subject |
degradation kinetic |
|
dc.subject |
enzyme inhibitor |
|
dc.subject |
formulation characterization |
|
dc.subject |
luminal and mucosal homogenates |
|
dc.subject |
nanocarriers |
|
dc.subject |
oral delivery |
|
dc.subject |
rat intestine |
|
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
|
dc.title |
Exploring ex vivo peptideolysis of thymopentin and lipid-based nanocarriers towards oral formulations. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1016/j.ijpharm.2022.122123 |
|
pubs.begin-page |
122123 |
|
dc.date.updated |
2022-08-28T22:37:25Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
35995317 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/35995317 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
|
pubs.elements-id |
916520 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Molecular Medicine |
|
pubs.org-id |
Pharmacy |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
dc.identifier.eissn |
1873-3476 |
|
dc.identifier.pii |
S0378-5173(22)00677-9 |
|
pubs.number |
122123 |
|
pubs.record-created-at-source-date |
2022-08-29 |
|