This technology is a nanoparticle-based drug that can be administered orally for effective systemic delivery and sustained release of appetite-suppressing hormone lipocalin-2 (LCN2) to treat obesity.
Unmet Need: Effective but patient-friendly drug for treatment of obesity
Current methods of treating obesity with hormone agonists to repress appetite have been effective in reducing weight, but their method of delivery — subcutaneous injection — poses an obstacle to patient adherence to treatment. While switching to oral formulations can improve medication adherence, safely delivering hormones at effective doses to the bloodstream is a challenge because of the stomach’s acidic environment and the intestinal epithelium’s limited permeability.
The Technology: Efficacious, extended-release oral formulation of hunger-suppressing hormone
This technology is an orally administered obesity treatment, called LIGNOCAL, that is designed to enable high bioavailability of appetite-suppressing hormone lipocalin-2 (LCN2) through nanoencapsulation. The polymers used to encapsulate LCN2 into nanoparticles are designed to safeguard the hormone across the wide pH range of the gastrointestinal tract and facilitate its crossing into the bloodstream while showing low cytotoxicity. Sustained release of LCN2 by the nanoparticles into the bloodstream maintains a bioactive systemic LCN2 concentration for at least two days and enables delivery of LCN2 to the hypothalamus, pancreas, and fatty tissues where LCN2 decreases appetite, increases beta islet cells, insulin secretion, and energy expenditure, and maintains glucose metabolism to exert its weight-regulatory effects.
This technology and its short-term weight loss effect have been validated in LCN2 knockout mice. Cytotoxicity screening of this technology has been conducted in hematopoietic stem cells. The effects of LCN2 have been validated in lean or obese mice and non-human primates.
Applications:
- Treatment for obesity and diabetes
- Prevention of cardiovascular diseases and other diseases associated with obesity
- Research tool for obesity, diabetes, metabolism, appetite, endocrine system, and endocrine function of bone
- Oral delivery of other macromolecules
- Weight loss drug
Advantages:
- Oral formulation for better patient compliance
- Effective systemic delivery
- Sustained release for maintaining bioactive systemic concentration
- Utilizes a short half-life and fast-acting hormone
- Low cytotoxicity
Lead Inventor:
Kam Leong, Ph.D.
Patent Information:
Patent Pending
Related Publications:
Yoshinaga N, Zhou JK, Xu C, Quek CH, Zhu Y, Tang D, Hung LY, Najjar SA, Shiu CYA, Margolis KG, Lao YH, Leong KW. “Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.” Nano Lett. 2023 Feb 8; 23(3): 757-764.
Petropoulou PI, Mosialou I, Shikhel S, Hao L, Panitsas K, Bisikirska B, Luo N, Bahna F, Kim J, Carberry P, Zanderigo F, Simpson N, Bakalian M, Kassir S, Shapiro L, Underwood MD, May CM, Soligapuram Sai KK, Jorgensen MJ, Confavreux CB, Shapses S, Laferrère B, Mintz A, Mann JJ, Rubin M, Kousteni S. “Lipocalin-2 is an anorexigenic signal in primates.” Elife. 2020 Nov 24; 9: e58949.
Mosialou I, Shikhel S, Luo N, Petropoulou PI, Panitsas K, Bisikirska B, Rothman NJ, Tenta R, Cariou B, Wargny M, Sornay-Rendu E, Nickolas T, Rubin M, Confavreux CB, Kousteni S. “Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes.” J Exp Med. 2020 Oct 5; 217(10): e20191261.
Mosialou I, Shikhel S, Liu JM, Maurizi A, Luo N, He Z, Huang Y, Zong H, Friedman RA, Barasch J, Lanzano P, Deng L, Leibel RL, Rubin M, Nickolas T, Chung W, Zeltser LM, Williams KW, Pessin JE, Kousteni S. “MC4R-dependent suppression of appetite by bone-derived lipocalin 2.” Nature. 2017 Mar 16; 543(7645): 385-390.
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