Immunoengineering Biomaterials in Cell-Based Therapy for Type 1 Diabetes.

Type 1 diabetes (T1D) is caused by low insulin production and chronic hyperglycemia due to destruction of pancreatic ß-cells. Cell transplantation is an attractive alternative approach compared to insulin injection. However, cell therapy has been limited by major challenges, including life-long requirement for immunosuppressive drugs to prevent host immune responses. Encapsulation of the transplanted cells can solve the problem of immune rejection, by providing a physical barrier between the transplanted cells and the recipient's immune cells. Despite current disputes in cell encapsulation approaches, thanks to recent advances in the fields of biomaterials and transplantation immunology, extensive effort has been dedicated to immunoengineering strategies, in combination with encapsulation technologies, to overcome the problem of host's immune responses. This review summarizes the most commonly used encapsulation and immunoengineering strategies combined with cell therapy, which have been applied as a novel approach to improve cell replacement therapies for management of T1D. Recent advances in the fields of biomaterial design, nanotechnology, as well as deeper knowledge about immune modulation had significantly improved cell encapsulation strategies. However, further progress requires combined application of novel immunoengineering approaches and islet/ß-cell transplantation. Impact statement Cell encapsulation shows promising potential in preventing host's immune responses and rejection of islets or ß-cells by providing a selectively permeable barrier between the host and the transplanted cells. Innovative materials, conformal nanocoatings, and immunomodulation have provided promising approaches in the field of encapsulation technology. Novel nanocarriers have been synthesized to release and deliver immunosuppressive agents to islets/ß-cells within the capsules in a controlled manner. The immunoengineering approach (immunosuppressive and immunomodulatory agents) could overcome the challenges of cell replacement therapy in type 1 diabetes.

Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation.

Solid lipid nanoparticle (SLN) is a promising approach for delivery of various drugs including proteins and peptides. However, the loading of hydrophilic drugs into the lipoid matrix of SLNs is challenging. The statistical design is a potential method facilitating the optimization of nanoparticles characteristics. In this study, the Box-Behnken design was conducted to optimize the preparation of Erythropoietin (EPO) loaded SLNs. Circular dichroism, size exclusion chromatography, SDS-PAGE, and ELISA tests were used to prove the compatibility of the process with the stability of EPO. In the controlled situation, EPO preserved its conformation and activity during the SLN preparation. Regarding the particle size, entrapment efficiency, and polydispersity index, an optimum formulation was obtained with 130 mg Span®80, 152.5 µl EPO, and 1.9 min high-shear homogenization. Using the optimum condition, 280 nm sized SLNs with the narrow size distribution of 0.282 and entrapment efficiency of 43.4% were acquired. The in vitro cytotoxicity of optimum SLN formulation was conducted using MTT assay to show its safety on the evaluated cell line. The in vivo studies demonstrated that 2500 U EPO loaded SLN has similar or even better effects on elevating the RBC, hemoglobin, and hematocrit level compared to the 5000 U EPO solution. Generally, this study proposed a suitable EPO-loaded SLN preparation method as a potential drug delivery system for proteins.