Hydrophilic polyacrylates for the microencapsulation of fibroblasts or pancreatic islets

Abstract

Viable mammalian cells have been microencapsulated in several water insoluble polyacrylates using organic solvents and nonsolvents and interfacial precipitation. Microencapsulated mammalian cells present a novel approach to the controlled delivery of biologically active molecules. By enclosing cells in an inert, semipermeable biocompatible membrane they may be implanted into an appropriate tissue cavity. There, either continuously or in response to specific physiological stimuli, the encapsulated cells secrete the desired therapeutic agent, while the membrane isolates the cells from the host's immune system. In our work we have focussed on the use of water insoluble polyacrylates rather than alginate and polylysine because of the potentially greater biocompatibility of the polyacrylates and the capability to tailor the polymer for particular applications or cell lines. Pancreatic islets were encapsulated in a commercially available cationic polyacrylate (Eudragit RL) as a model system. Although the polymer was neither permeable nor biocompatible enough, the islets continued to secrete insulin in a static glucose challenge assay for > 3 months after encapsulation, demonstrating the general utility of these techniques for islets and water insoluble polyacrylates. Anchorage dependent human diploid fibroblasts (HDF), encapsulated in a 16% dimethylaminoethyl methacrylate-methyl methacrylate copolymer (DMAEMA-MMA) attached to the capsule wall and grew but only in those capsules which were broken or flawed, indicating the importance of permeability restrictions to the growth of encapsulated cells. Chinese hamster ovary (CHO) cells, encapsulated in a potentially biocompatible 75% 2-hydroxyethyl methacrylate-MMA (HEMA-MMA) copolymer were alive but also did not grow after encapsulation, presumably because of space limitations. Although further work is required these studies demonstrate the feasibility of using water insoluble polyacrylates for cell microencapsulation and ultimately for drug delivery by transplanted viable cells.