Christine Hiemstra

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

Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that blocks several angiogenesis related pathways. The aim of this study was to develop sunitinib-loaded polymeric microspheres that can be used as intravitreal formulation for the treatment of ocular diseases. A series of novel multi-block copolymers composed of amorphous blocks of poly-(D,L-lactide) (PDLLA) and polyethylene glycol (PEG) and of semi-crystalline poly-(L-lactide) (PLLA) blocks were synthesized. Sunitinib-loaded microspheres were prepared by a single emulsion method using dichloromethane as volatile solvent and DMSO as co-solvent. SEM images showed that the prepared microspheres (∼ 30 μm) were spherical with a non-porous surface. Sunitinib-loaded microspheres were studied for their degradation and in-vitro release behavior. It was found that increasing the percentage of amorphous soft blocks from 10% to 30% accelerated the degradation of the multi-block copolymers. Sunitinib microspheres released their cargo for a period of at least 210 days by a combination of diffusion and polymer erosion. The initial burst (release in 24h) and release rate could be tailored by controlling the PEG-content of the multi-block copolymers. Sunitinib-loaded microspheres suppressed angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These microspheres therefore hold promise for long-term suppression of ocular neovascularization.

Stereocomplexed PEG-PLA Hydrogels

In this paper we give an overview of our studies on stereocomplexed hydrogels upon mixing aqueous solutions of enantiomeric linear poly (ethylene glycol)-poly(L-lactide) triblock (PEG-PLA) copolymers and eight-arm (PEG-PLA) star block copolymers and methacrylate functionalized PEG-PLA star block copolymers [1, 2, 3]. Stereocomplexation and photopolymerization were combined and enhanced the stability of the hydrogels. For all polymers, the critical gel concentrations of the mixed enantiomer solutions were considerably lower compared to polymer solutions containing only the single enantiomer. The gel-sol transition temperatures were increased and gel regions were expanded due to stereocomplexation.