Microencapsulation for therapeutic applications

Microencapsulation has proved to be a powerful technique in the field of drug delivery. A great deal of research is directed towards studying the use of various microencapsulation systems for that purpose. This study investigates the use of microencapsulation in alginate for protein delivery and delivery of gene therapy products for the treatment of spinal cord injury. Liposomes were encapsulated in alginate to form a drug delivery system which allows for multiple control points for drug release. We found that the crosslinking ion has a marked effect on the release profile. PC/Chol and PC/PG/Chol liposomes encapsulated in Ca²⁺ crosslinked alginate released protein rapidly in the form of a burst which was eliminated by crosslinking the alginate with Ba2+. Liposome composition also plays an important role in the release from microencapsulated liposomes. DOPC and DOPC/Chol liposomes showed a delayed pulse of protein release which could be useful for vaccine delivery. Unextruded REV's demonstrated the capability of obtaining protein release in a pulsatile manner after encapsulation in alginate. Our studies also showed that encapsulation in alginate made the liposomes leakier and this was the result of a co-operative effect of alginate and the crosslinking ions. Fibroblasts that were genetically engineered to produce BDNF were encapsulated in alginate. In vitro studies showed that the encapsulated cells continue to grow, express the transgene and BDNF is released from the microcapsules in an active form. These encapsulated cells were transplanted into the injured spinal cord of rats that were not immune suppressed. We found that the encapsulated cells survived in vivo and continued to express the transgene. This showed that encapsulation protected the cells from the host immune system. The transplanted capsules evoked a non-specific immune response and also resulted in sprouting of axons in the transplant area. The axonal growth observed increased with time. Behavioral studies showed a recovery of function in the injured forelimb of the rats almost up to baseline levels over 5 weeks. Finally, we studied a peptide-alginate conjugate as a permissive surface for growth of neurons such that it could be applied in combination with the encapsulated cells.