Biphasic Hydrogel-Microsphere Formulation for Restenosis Prevention
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Solution Overview
Problem
Current treatments for preventing restenosis after open surgical revascularization lack effective local drug delivery methods, leading to systemic side effects and limited success due to the inability to maintain drug formulations at the treatment site for an optimal duration, with existing hydrogel formulations rapidly degrading and failing to provide a sustained release profile.
Innovation Solution
A pharmaceutical formulation comprising a hydrogel phase with a rapidly delivered compound for the acute inflammatory phase and sustained release microspheres for later phases of restenosis development, using biocompatible and biodegradable materials like hyaluronic acid and PLGA, ensuring localized drug delivery and extended release kinetics up to several weeks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a local drug delivery formulation is applied at the site of surgery, then the efficiency and safety of preventing restenosis is improved, but the formulation must remain stable at the site for an optimal duration which conflicts with the need for biodegradability
Solution Approach 1:
The formulation is segmented into two distinct components: a hydrogel phase for immediate drug delivery and microspheres for sustained release. This segmentation allows each component to fulfill its specific function - the hydrogel provides initial stability and rapid drug release, while the microspheres ensure long-term persistence and continued drug delivery, thereby resolving the contradiction between stability and biodegradability.
Solution Approach 2:
The invention uses a composite formulation combining hydrogel and microsphere materials with different degradation profiles. The hydrogel phase degrades rapidly to provide initial drug release, while the microsphere phase degrades slowly to maintain drug presence over weeks. This composite approach allows the formulation to be both stable enough for long-term action and biodegradable for elimination without surgery.
2Duration of action of stationary object
If a sustained release formulation is used to maintain drug presence at the site, then the duration of action is improved, but the release profile may not match the optimal time schedule of pathology development
Solution Approach 1:
The drug delivery system is divided into two segments with different release characteristics: the hydrogel phase releases drugs rapidly to address acute inflammatory phase, while the microsphere phase releases drugs slowly for later phases of restenosis development. This temporal segmentation allows the formulation to adapt to different stages of pathology, resolving the contradiction between sustained release duration and release profile matching.
Solution Approach 2:
The formulation implements periodic drug release through its two-phase structure, with an initial rapid release phase from the hydrogel followed by a sustained release phase from the microspheres. This periodic action pattern matches the natural progression of restenosis pathology, providing high drug concentrations when needed acutely and lower sustained levels for long-term prevention.
3Object-affected harmful factors
If biocompatible and biodegradable polymers are used for drug delivery, then the safety and eliminability of the formulation is improved, but the ability to achieve long term local permanence and controlled release is limited
Solution Approach 1:
The formulation combines biocompatible and biodegradable materials with different degradation rates - the hydrogel phase degrades quickly while the microsphere phase degrades slowly. This composite material strategy maintains biocompatibility and biodegradability (avoiding surgery for removal) while achieving long-term local permanence through the sustained degradation and drug release from the microsphere component.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation effectively reduces vascular smooth muscle cell viability and migration, inhibits intimal hyperplasia, and provides a controlled release of drugs like atorvastatin and aspirin, significantly decreasing restenosis development and intimal thickness, with sustained release profiles maintaining therapeutic effects for up to 4 weeks.
Implementation Method 1
using biocompatible and biodegradable materials like hyaluronic acid
Implementation Method 2
rapidly delivered compound effective on the acute inflammatory phase
Implementation Method 3
sustained release formulation comprising at least one compound effective on later phases of restenosis development
Implementation Method 4
sustained release profiles maintaining therapeutic effects for up to 4 weeks
Implementation Method 5
To be efficient a local therapy needs to stay located at the site of administration
Implementation Method 6
The hydrogel, due to its inherent viscosity, will ensure the localization of the drug delivery system
Implementation Method 7
This formulation needs also to be biocompatible and biodegradable to be eliminated via either hydrolysis or enzymolysis
Implementation Method 8
eliminated via either hydrolysis or enzymolysis to avoid a second surgery
Data Source
AI summary
The present invention relates generally to a pharmaceutical formulation for use in the treatment and/or prevention of restenosis in a subject in need thereof. Methods of treatment and/or prevention are also provided.