Physicochemical and Biopharmaceutical Controllability of New Self-Assembled Fatty Acid Conjugated Leuprolide for the Enhanced Anticancer Activity

• DOI: 10.2147/ijn.s401048
• Publication Date: 2023-05-03T23:45:07Z
• Authors: Hai V Ngo; Hye-Eun Bak; Hy D Nguyen; Kye Wan Lee; Chulhun Park; Beom-Jin Lee
• Keywords: Conjugate; Biopharmaceutical

Leuprolide (LEU), a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH), could exert direct inhibitory activity on the proliferation prostate cancer cells. However, short half-life in blood and biopharmaceutical problem LEU limit this anticancer activity.To improve its druggability for improving activity, amine-group targeted was conjugated with different chain lengths saturated fatty acids (FAs).LEU-fatty acid conjugates (LFCs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry. The physicochemical properties self-assembled behaviors extensively investigated. vitro three LFCs studied both 2D monolayer 3D spheroid culture models cell line, PC3.Three be readily into nanoparticles (LFNs) small size around 100 nm, positive charges, exhibited greater permeability rates compared to same concentration LEU, excluding LSN. length FA conjugate positively related selectivity index between cells non-cancerous lines. All showed superior antiproliferative effect following order: LSC (98.9%) > LPC (86.7%) LLC (75.0%) (8.9%) after repeat daily dose strength 4 days. In addition, model study indicates that all one-time treatment performed long-acting tumor growth as 7 days.The FAs provide novel strategy peptide stability an additional several hormone-responsive systems using therapeutic peptides.