Stealth Liposomal PGI2 Agonist Formulation for Site-Specific Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for producing disease-site-specific nanosphere formulations containing a PGI2 receptor agonist, such as ONO-1301, face challenges with stability, content, yield, safety, sustained release rate, and efficacy, making it difficult to achieve effective accumulation at disease sites while minimizing side effects.
Innovation Solution
A stealth liposomal formulation is developed, utilizing a specific combination of phospholipids and PEG-modified phosphoethanolamine to control drug release and enhance accumulation at disease sites, with a particle size of 50 to 200 nm, improving bioavailability and reducing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compound (A) is administered orally or intravenously to achieve therapeutic effects, then drug efficacy is improved, but side effects such as diarrhea, vasodilation, and hypotension worsen due to high concentration exposure in the gastrointestinal tract or rapid blood concentration increase
Solution Approach 1:
The patent segments the drug delivery process by using liposomes to encapsulate compound (A), separating the drug from direct contact with the gastrointestinal tract and bloodstream. This segmentation allows controlled release at the target site while preventing systemic side effects.
Solution Approach 2:
The liposome acts as an intermediary carrier between the administration route and the target tissue. It mediates drug delivery by protecting compound (A) from premature release and facilitating targeted accumulation at disease sites through passive or active mechanisms.
2Duration of action of moving object
If microspheres with average particle diameter of about 30 μm are used for long-term sustained-release injectable formulations, then drug release control is improved, but the formulation lacks disease-site-specific accumulation capability due to insufficient DDS effect
Solution Approach 1:
The patent changes the particle size parameter from micrometer-scale (30 μm) to nanometer-scale (10-1000 nm) liposomes. This parameter change enables both sustained release and disease-site-specific accumulation by exploiting the enhanced permeability and retention effect at tumor sites while maintaining circulation time.
3Manufacturing precision
If nanosphere formulations are produced to achieve disease-site-specific accumulation, then DDS effect is improved, but stability, content, yield, and safety are worsened making clinically applicable production difficult
Solution Approach 1:
The patent uses composite liposomal materials combining phospholipids, cholesterol, and PEG-modified phospholipids to create stable nanospheres. This composite structure provides both the desired disease-site accumulation and the necessary stability for clinical production and storage.
4Quantity of substance
If MS formulation is administered by intravenous injection to maintain high drug concentration at administration site, then local drug concentration is improved, but safety worsens due to risk of pulmonary embolism from mass administration
Solution Approach 1:
The patent transitions from micrometer-scale to nanometer-scale particles, changing the dimensional scale of the delivery system. This dimensional change allows particles to circulate systemically without causing pulmonary embolism while still achieving targeted accumulation through passive targeting mechanisms at disease sites.
Data Source
AI summary
The present invention provides clinically applicable, safe and convenient, pharmaceutical compositions and methods for disease site-specific treatment. The pharmaceutical composition for disease site-specific treatment methods comprises a stealth liposome having a prostaglandin I2 receptor agonist encapsulated therein.