Sunitinib microspheres based on [PDLLA-PEG-PDLLA]-b-PLLA multi-block copolymers for ocular drug delivery.

Area of Science:

• Ophthalmology
• Biomaterials Science
• Pharmacology

Background:

• Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor crucial for blocking angiogenesis-related pathways.
• Ocular neovascularization is a significant factor in various eye diseases, necessitating effective therapeutic strategies.
• Intravitreal drug delivery systems are essential for localized and sustained treatment of ocular conditions.

Purpose of the Study:

• To develop and characterize sunitinib-loaded polymeric microspheres for intravitreal administration.
• To investigate the influence of copolymer composition on microsphere properties, degradation, and drug release.
• To evaluate the efficacy of the developed microspheres in suppressing ocular angiogenesis.

Main Methods:

• Synthesis of novel multi-block copolymers comprising poly-(D,L-lactide) (PDLLA), polyethylene glycol (PEG), and poly-(L-lactide) (PLLA).
• Preparation of sunitinib-loaded microspheres using a single emulsion method with dichloromethane and DMSO.
• Characterization of microsphere morphology (SEM), degradation, in-vitro drug release kinetics, and anti-angiogenic activity (CAM assay).

Main Results:

• Spherical microspheres (∼30 μm) with non-porous surfaces were successfully prepared.
• Increased amorphous soft block content (10-30%) accelerated copolymer degradation.
• Sunitinib release occurred over at least 210 days via diffusion and polymer erosion, tunable by PEG content.
• Initial burst release and release rate were controllable through PEG content.
• Microspheres demonstrated significant suppression of angiogenesis in the CAM assay.

Conclusions:

• Novel sunitinib-loaded polymeric microspheres were successfully developed for intravitreal application.
• The degradation and drug release profiles can be precisely controlled by adjusting the copolymer composition, particularly PEG content.
• These microspheres show significant potential for long-term suppression of ocular neovascularization, offering a promising therapeutic approach for eye diseases.