title: Design of a composite drug delivery system to prolong functionality of cell-based scaffolds.
abstract: 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.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, School of Pharmacy, Vitoria-Gasteiz, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Murua
authors.forename: Enara
authors.initials: E
authors.lastname: Herran
authors.forename: Gorka
authors.initials: G
authors.lastname: Orive
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Blanco
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Hernández
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D002214:Capsules; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004343:Drug Implants; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D005782:Gels; D005938:Glucocorticoids / Q000008:administration & dosage*; D006400:Hematocrit; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008863:Microspheres; D032446:Myoblasts / Q000637:transplantation*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D013997:Time Factors; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; D005938:Glucocorticoids; C051546:alginate-polylysine-alginate; D004921:Erythropoietin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone