Release and bioactivity of PACA nanoparticles containing D-Lys6-GnRH for brushtail possum fertility control
Kafka, Alexandra; McLeod, Bernie; Rades, Thomas; McDowell, Arlene
Poly(ethylcyanoacrylate) (PECA) nanoparticles containing the chemical sterilitant D-Lys6-GnRH were prepared by an in situ interfacial polymerization technique. Their potential as a peroral delivery system for biocontrol of the brushtail possum, a major pest species in New Zealand, was evaluated. Peptide release from resulting particles was studied in vitro in artificial gastric juice (AGJ), simulated intestinal fluids (SIF) and brushtail possum plasma. The nanoparticles released a small fraction of bioactive over 6 hours in AGJ and SIF (< 5%), whilst staying intact and retaining fractions of intact D-Lys6-GnRH. In contrast, 60% of D-Lys6-GnRH was released after 1 hour in possum plasma. The nanoparticles were also administered in vivo into the caecum of brushtail possums. A significant biological response, measured as an increase in plasma luteinizing hormone (LH), was evident 10 minutes after administration. This demonstrates not only that PECA nanoparticles were able to facilitate the uptake of D-Lys6-GnRH from the caecum into systemic circulation, but also that sufficient bioactive peptide reached the pituitary to exert a significant LH response following GnRH receptor mediated endocytosis. Hence, it can be concluded, that PECA nanoparticles comprise a promising formulation strategy for the peroral delivery of the chemical sterilitant D-Lys6-GnRH to the brushtail possum in New Zealand.
Rights Statement: This version in OUR Archive is the author’s manuscript accepted for publication after peer-review. The published version is: Kafka AP, McLeod BJ, Rades T, McDowell A. Release and bioactivity of PACA nanoparticles containing D-Lys⁶-GnRH for brushtail possum fertility control. Journal of Controlled Release : Official Journal of the Controlled Release Society. 2011 Feb;149(3):307-313. DOI: 10.1016/j.jconrel.2010.10.029. PMID: 21047541. This OUR Archive version is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: PACA nanoparticles; GnRH; peptide polymer conjugates; brushtail possum; oral delivery; fertility control
Research Type: Journal Article
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