Nanoparticle technology for sustained release of therapeutic agents

This invention describes lipid-based nanoparticles designed for encapsulating and slowly releasing therapeutic agents, such as siRNA, to treat diseases. These nanoparticles enhance drug delivery efficiency and minimize rapid release, improving treatment outcomes and reducing side effects.

Background

Chronic inflammation-related diseases, such as rheumatoid arthritis, present significant treatment challenges due to the complexity of the immune response and the need for targeted delivery of therapeutic agents. Traditional therapies, like anti-TNF-α drugs, have shown efficacy but often come with limitations such as systemic side effects and the need for frequent dosing. Small interfering RNA (siRNA) has emerged as a promising therapeutic approach due to its ability to selectively silence pro-inflammatory cytokines like TNF-α. However, siRNA therapy is hindered by its short half-life, poor cellular uptake, and potential immunogenicity.

Nanoparticle delivery systems have been explored to overcome these challenges, aiming to improve siRNA stability and delivery efficiency. Despite advancements, existing nanoparticle formulations often suffer from high burst release rates, leading to rapid drug release and reduced therapeutic efficacy. Additionally, achieving high encapsulation efficiency while maintaining low burst release remains a challenge.

Many formulations struggle with balancing these factors, often resulting in nanoparticles that either release too much of the drug too quickly or fail to encapsulate enough of the therapeutic agent. These limitations highlight the need for nanoparticle formulations that can provide both high encapsulation efficiency and controlled, sustained release of therapeutic agents.

Technology description

This technology involves the development of lipid-based nanoparticles designed for the encapsulation and sustained release of therapeutic agents. The nanoparticles feature a lipid core that includes a sterol, within which a complex of a cationic agent and a therapeutic agent is encapsulated. The production process involves combining a cationic agent, a therapeutic agent, and a water-immiscible solvent with an aqueous solution to form a complex. This complex is then separated into an organic phase, mixed with a sterol and a water-miscible organic solvent, and finally dispersed in a second aqueous solution to form the nanoparticles.

These nanoparticles are engineered to encapsulate therapeutic agents efficiently, ensuring a controlled and sustained release, which can be particularly beneficial for treating diseases and minimizing the initial burst release of the therapeutic agent.

The differentiation of this technology lies in its ability to achieve high encapsulation efficiency and minimal burst release of therapeutic agents, which are common challenges in nanoparticle drug delivery systems. The inclusion of a sterol in the lipid core and the specific method of preparation contribute to the stability and controlled release properties of the nanoparticles. Additionally, the use of an acid-sensitive sheddable PEG layer enhances the targeting and retention of the nanoparticles in specific sites, such as inflamed tissues, by responding to the local pH environment.

This targeted delivery system not only improves the therapeutic efficacy of the encapsulated agents but also reduces potential systemic side effects, making it a significant advancement in the field of nanomedicine.