Design of a composite drug delivery system to prolong functionality of cell-based scaffolds

• Published in: International journal of pharmaceutics 2011-04, Vol.407 (1), p.142-150
• Main Authors: Murua, Ainhoa, Herran, Enara, Orive, Gorka, Igartua, Manoli, Blanco, Francisco Javier, Pedraz, José Luis, Hernández, Rosa Mª
• Format: Article
• Language: English
• Subjects: Alginate; Alginates - chemistry; Animals; Antiinflammatory agents; Biocompatibility; Biocompatible Materials - administration & dosage; Biological and medical sciences; Capsules; Delayed-Action Preparations; Dexamethasone; Dexamethasone - administration & dosage; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug development; Drug Implants; Encapsulation; Erythropoietin; Erythropoietin - secretion; Female; Gels; General pharmacology; Glucocorticoids - administration & dosage; Hematocrit; Immunosuppression; Inflammation; Lactic Acid - chemistry; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Microencapsulation; Microspheres; Myoblasts; Myoblasts - transplantation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA; Polyglycolic Acid - chemistry; polylactide-co-glycolide; Polylysine - analogs & derivatives; Polylysine - chemistry; scaffolds; Time Factors; Tissue Scaffolds
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.11.022

Co-implantation of DXM-loaded PLGA microspheres resulted in improved functionality of the cell-based grafts during 45 days in allogeneic mice. Cell encapsulation technology raises hopes in medicine and biotechnology. However, despite important advances in the field in the past three decades, several challenges associated with the biocompatibility are still remaining. In the present study, the effect of a temporary release of an anti-inflammatory agent on co-administered encapsulated allogeneic cells was investigated. The aim was to determine the biocompatibility and efficacy of the approach to prevent the inflammatory response. A composite delivery system comprised of alginate-poly- l-lysine-alginate (APA)-microencapsulated Epo-secreting myoblasts and dexamethasone (DXM)-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres was implanted in the subcutaneous space of Balb/c mice for 45 days. The use of independently co-implanted DXM-loaded PLGA microspheres resulted in an improved functionality of the cell-based graft, evidenced by significantly higher hematocrit levels found in the cell-implanted groups by day 45, which was found to be more pronounced when higher cell-doses (100 μL) were employed. Moreover, no major host reaction was observed upon implantation of the systems, showing good biocompatibility and capability to partially avoid the inflammatory response, probably due to the immunosuppressive effects related to DXM. The findings of this study imply that DXM-loaded PLGA microspheres show promise as release systems to enhance biocompatibility and offer advantage in the development of long-lasting and effective implantable microencapsulated cells by generating a potential immunopriviledged local environment and an effective method to limit the structural ensheathing layer caused by inflammation.