Controlled Release Formulations for the Delivery of HIF-1 Inhibitors

摘要

Controlled release dosage formulations for the delivery of one or more HIF-1 inhibitors are provided. The controlled release formulations contain one or more HIF-1 inhibitors conjugated to or dispersed in a polymeric vehicle. The one or more HIF-1 inhibitors can be dispersed or encapsulated in a polymeric matrix. In some embodiments, the one or more HIF-1 inhibitors are covalently bound to a polymer, forming a polymer-drug conjugate. Polymeric vehicles can be formed into implants, microparticles, nanoparticles, or combinations thereof. Controlled release HIF-1 formulations provide prolonged therapeutic benefit while lowering side effects by releasing low levels of one or more HIF-1 inhibitors and/or HIF-1 inhibitor conjugates over a prolonged period of time. Controlled release dosage formulations can be used to treat or prevent a disease or disorder in a patient associated with vascularization, including cancer, obesity, and ocular diseases such as wet AMD.

主权项

1. A population of micro- and/or nanoparticles formed of polymeric conjugates defined by one of the following formulae
(A-X)m—Y—((Z)o—(X)p-(A)q)n wherein
A represents, independently for each occurrence, a HIF-1 inhibitor; X represents, independently for each occurrence, a hydrophobic polymer segment; Y is absent, or represents a branch point; Z represents, independently for each occurrence, a hydrophilic polymer segment; and o, p, and q are independent 0 or 1; m is an integer between one and twenty; and n is an integer between zero and twenty, wherein solubility of the conjugate can be controlled by modifying the solubility of the polymer portion and/or the branched point Y to minimize soluble HIF-1 inhibitor concentration.