Release and bioactivity of PACA nanoparticles containing D-Lys⁶-GnRH for brushtail possum fertility control.
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 6h in AGJ and SIF (<5%), while staying intact and retaining fractions of intact D-Lys⁶-GnRH. In contrast, 60% of D-Lys⁶-GnRH was released after 1h 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 min 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.
School of Pharmacy, University of Otago, Dunedin 9054, New Zealand. alexandra.kafka@coriolis-pharma.com
Alexandra P
AP
Kafka
Bernie J
BJ
McLeod
Thomas
T
Rades
Arlene
A
McDowell
D000818:Animals; D003270:Contraceptive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003487:Cyanoacrylates / Q000737:chemistry*; D005298:Fertility; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008394:Marsupialia / Q000254:growth & development*; D053758:Nanoparticles / Q000737:chemistry*; D009520:New Zealand
D003270:Contraceptive Agents; D003487:Cyanoacrylates; C558475:poly(ethylcyanoacrylate); D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone