Nanoparticles for preventing peri/post-menopausal bone loss and/or obesity
Inventors
MohanKumar, Sheba M. J. • MohanKumar, Puliyur S. • Chuang, Yen-jun
Assignees
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Publication Number
US-12214085-B2
Publication Date
2025-02-04
Expiration Date
Abstract
Nanoparticles and formulations for preventing or reducing peri-/post-menopausal bone loss and/or obesity in a subject are disclosed. The nanoparticles contain a cage, such as a zeolitic imidazolate framework (“ZIF”), a surface modifying agent, a targeting ligand, and an active agent. The surface modifying agent is attached to the outer surface of the cage and the targeting ligand is exposed to the surrounding environment. The active agent is encapsulated in the cage. The targeting ligand binds to a reproductive hormone or a receptor of a reproductive hormone. The active agent can be a ribosome inactivating protein, an apoptosis inducer, a hormone, a receptor ligand, or a nucleic acid, or a combination thereof, that inactivate ribosomes of gonadotroph cells and/or prevent or reduce secretion of follicle-stimulating hormones in the subject. Uses for formulations incorporating the nanoparticles for preventing or reducing peri-/post-menopausal bone loss and/or obesity in a subject are also disclosed.
Core Innovation
The invention provides a pharmaceutical formulation for preventing or reducing peri-/post-menopausal bone loss and/or obesity in a subject using nanoparticles. The nanoparticles include a cage made of a zeolitic imidazolate framework (ZIF), a surface modifying agent attached to an outer surface of the cage, and a targeting ligand exposed to a surrounding environment.
The targeting ligand is a gonadotropin-releasing hormone (GnRH) receptor agonist, a follicle stimulating hormone (FSH) receptor agonist, a luteinizing hormone (LH) receptor agonist, or a combination thereof. The active agent is encapsulated in the cage, and the formulation further includes a pharmaceutically acceptable carrier and/or excipient.
The formulation is described with lysosome-activated/acid-labile degradation for release under acidic conditions and with an overall neutral/near-neutral charge. The document also links the use of the GnRH-targeting pharmaceutical formulation to therapeutic outcomes involving ribosome inactivation and apoptosis of gonadotrophs, along with reduced follicle stimulating hormone (FSH) secretion and levels.
Claims Coverage
The independent claim coverage centers on a ZIF-caged nanoparticle formulation with an attached surface modifying agent and an exposed receptor-agonist targeting ligand, where an active agent is encapsulated and the formulation includes a pharmaceutically acceptable carrier and/or excipient. The coverage includes 2 inventive features in the independent claim presentation, with dependent limitations on ZIF selection, conjugation extent, nanoparticle physical properties, and administration routes.
ZIF-caged nanoparticle formulation with external receptor-agonist targeting ligand
A pharmaceutical formulation for preventing or reducing peri-/post-menopausal bone loss and/or obesity comprising a plurality of nanoparticles with a zeolitic imidazolate framework (ZIF) cage, a surface modifying agent attached to an outer surface of the cage, and a targeting ligand exposed to a surrounding environment, where the targeting ligand is a GnRH receptor agonist, or a follicle stimulating hormone (FSH) receptor agonist, or a luteinizing hormone (LH) receptor agonist, or a combination thereof.
Encapsulated active agent within ZIF cage and pharmaceutically acceptable carrier
The plurality of nanoparticles includes a cage that encapsulates an active agent, and the pharmaceutical formulation comprises the nanoparticles together with a pharmaceutically acceptable carrier and/or excipient.
Overall, the claims cover ZIF-caged nanoparticles that encapsulate an active agent, include a surface modifying agent on the outer cage surface, and expose a gonadotropin receptor agonist targeting ligand to the surrounding environment, formulated with a pharmaceutically acceptable carrier/excipient.
Stated Advantages
Prevents or reduces peri-/post-menopausal bone loss and/or obesity in a subject.
Achieves therapeutic outcomes associated with ribosome inactivation and apoptosis of gonadotrophs.
Reduces follicle stimulating hormone (FSH) secretion and FSH levels.
Documented Applications
Prevention or reduction of peri-/post-menopausal bone loss and/or obesity in a subject using the disclosed pharmaceutical formulation.
Therapeutic context targeting gonadotrophs with outcomes described as ribosome inactivation and apoptosis and reduced FSH secretion/levels.
Use of parenteral administration formats including intramuscular administration, intravenous administration, intraperitoneal administration, and subcutaneous administration.
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