Microcapsules and microcarriers for in situ cell delivery.

In recent years, the use of transplanted living cells pumping out active factors directly at the site has proven to be an emergent technology. However a recurring impediment to rapid development in the field is the immune rejection of transplanted allo- or xenogeneic cells. Immunosuppression is used clinically to prevent rejection of organ and cell transplants in humans, but prolonged usage can make the recipient vulnerable to infections, and increase the likelihood of tumorigenesis of the transplanted cells. Cell microencapsulation is a promising tool to overcome these drawbacks. It consists of surrounding cells with a semipermeable polymeric membrane. The latter permits the entry of nutrients and the exit of therapeutic protein products, obtaining in this way a sustained delivery of the desirable molecule. The membrane isolates the enclosed cells from the host immune system, preventing the recognition of the immobilization cells as foreign. This review paper intends to overview the current situation in the cell encapsulation field and discusses the main events that have occurred along the way. The technical advances together with the ever increasing knowledge and experience in the field will undoubtedly lead to the realization of the full potential of cell encapsulation in the future.

Bioactive cell-hydrogel microcapsules for cell-based drug delivery.

Improvement of long-term drug release and design of mechanically more stable encapsulation devices are still major challenges in the field of cell encapsulation. This may be in part due to the weak in vivo stability of calcium-alginate beads and to the use of inactive biomaterials and inert scaffolds that do not mimic the physiological situation of the normal cell milieu. We hypothesized that designing biomimetic cell-hydrogel capsules might promote the in vivo long-term functionality of the enclosed drug-secreting cells and improve the mechanical stability of the capsules. Biomimetic capsules were fabricated by coupling the adhesion peptide arginine glycine aspartic acid (RGD) to alginate polymer chains and by using an alginate-mixture providing a bimodal molecular weight distribution. The biomimetic capsules provide cell adhesion for the enclosed cells, potentially also leading to mechanical stabilization of the cell-polymer system. Strikingly, the novel cell-hydrogel system significantly prolonged the in vivo long-term functionality and drug release, providing a sustained erythropoietin delivery during 300 days without immunosuppressive protocols. Additionally, controlling the cell-dose within the biomimetic capsules enables a controlled in vitro and in vivo drug delivery. Biomimetic cell-hydrogel capsules provide a unique microenvironment for the in vivo long-term de novo delivery of drugs from immobilized cells.

Gamma-irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine.

Gamma-irradiation is currently the method of choice for terminal sterilization of drug delivery systems made from biodegradable polymers. However, the consequences of gamma-sterilization on the immune response induced by microencapsulated antigens have not yet been reported in the literature. The aim of the present work was to evaluate the effect of gamma-irradiation on the biopharmaceutical properties of PLGA microspheres containing SPf66 malarial antigen. Microspheres were prepared by a (w/o/w) double emulsion/solvent extraction method. Once prepared, part of the formulation was irradiated at a dose of 25 kGy using 60Co gamma as radiation source. The in vitro results obtained showed that the gamma-irradiation exposure had no apparent effect on SPf66 integrity and formulation properties such us morphology, size and peptide loading. Only the release rate of SPf66 was slightly faster after gamma-irradiation. Subcutaneous administration of irradiated and non-irradiated microspheres into mice induced a similar immune response (IgG, IgG1, IgG2a levels) and was comparable to that obtained with SPf66 emulsified with Freund's complete adjuvant. These observations illustrate the applicability of gamma-irradiation as a method of terminal sterilization of microparticulate delivery systems based on chemically synthesized antigens encapsulated into biodegradable PLGA microspheres.