Compositions and methods of using propylene sulfide-based polymers for treatment of Chagas disease
Inventors
Scott, Evan A. • Yi, Sijia • Engman, David • Li, Xiaomo
Assignees
Publication Number
US-12311054-B2
Publication Date
2025-05-27
Expiration Date
2040-07-29
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Abstract
The present invention provides novel nanostructures comprising solution of PPSU20. Methods of preparing the novel PPSU nanostructures, and applications of such nanostructures are also provided.
Core Innovation
The invention provides novel nanocarriers composed of poly(ethylene glycol)-block-poly(propylene sulfide) copolymers loaded with therapeutic agents, specifically for the treatment of Chagas disease caused by Trypanosoma cruzi. These nanostructures can encapsulate drugs such as Benznidazole, Nifurtimox, and other agents known for treating Chagas disease. The invention also includes compositions and methods for preparing and administering these nanocarriers.
The core problem addressed is the lack of effective and safe treatments for Chagas disease. Current therapies rely on long-term administration of drugs like Benznidazole and Nifurtimox, which have poor bioavailability, limited efficacy—especially in chronic cases—and are associated with severe side effects that frequently cause patients to discontinue treatment. There is a need for more effective therapies that can treat T. cruzi infection while minimizing these adverse effects.
The invention solves this problem by employing PEG-b-PPS nanocarriers to encapsulate and deliver therapeutic agents more efficiently to infected cells. These nanocarriers enhance cellular uptake and targeted delivery, enabling significantly lower drug dosages to achieve therapeutic efficacy. This not only improves drug potency but also greatly reduces the risk of side effects historically observed with conventional formulations. The nanocarriers can be formulated into pharmaceutical compositions for various routes of administration to treat Chagas disease in subjects.
Claims Coverage
The patent contains two independent claims, each describing inventive features centered on the use of poly(ethylene glycol)-block-poly(propylene sulfide) nanocarriers loaded with Benznidazole for treating Trypanosoma cruzi infection.
Method of treating Trypanosoma cruzi infection with PEG-b-PPS nanocarrier containing Benznidazole
A method of treating Trypanosoma cruzi infection in a subject by administering a pharmaceutical composition that contains: - A nanocarrier comprising poly(ethylene glycol)-block-poly(propylene sulfide) copolymer. - The therapeutic agent N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide (Benznidazole) encapsulated within the nanocarrier. Notably, the nanocarrier formulation permits the use of Benznidazole at much lower dosages compared to standard oral administration.
Pharmaceutical composition with PEG-b-PPS nanocarrier and Benznidazole for Chagas disease treatment
A pharmaceutical composition comprising: - A poly(ethylene glycol)-block-poly(propylene sulfide) copolymer nanocarrier. - Encapsulated N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide (Benznidazole). The composition is suitable for administering a therapeutically effective amount for treating Chagas disease, with the inventive aspect being the encapsulation of Benznidazole in the PEG-b-PPS nanocarrier to enable effective therapy at reduced dosages.
The independent claims focus on the use of PEG-b-PPS nanocarrier technology for encapsulating Benznidazole, enabling treatment of Trypanosoma cruzi infection at significantly lower drug doses and with reduced side effects.
Stated Advantages
The nanocarrier enables delivery of therapeutic agents at significantly lower dosages than required for free form drugs, reducing side effects and allowing longer-term use.
PEG-b-PPS nanocarriers enhance the bioavailability and intracellular delivery of Benznidazole, leading to improved therapeutic efficacy.
The system minimizes or eliminates common side effects such as neuropathy, dermatitis, pruritus, gastrointestinal manifestations, hepatic function alteration, and weight loss compared to traditional treatments.
Polymers used in the nanocarrier (poly(ethylene glycol) and poly(propylene sulfide)) are proven to be inert, contributing to the safety of the formulation.
The nanocarriers provide controlled release and targeted delivery of drugs to infected cells, reducing toxic effects.
Documented Applications
Treatment of Chagas disease (American trypanosomiasis) in subjects infected with Trypanosoma cruzi.
Use in pharmaceutical compositions for administration by a variety of routes, including intravenous, subcutaneous, and other parenteral methods.
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