title: Tracking immune-related cell responses to drug delivery microparticles in 3D dense collagen matrix.
abstract: Beyond the therapeutic purpose, the impact of drug delivery microparticles on the local tissue and inflammatory responses remains to be further elucidated specifically for reactions mediated by the host immune cells. Such immediate and prolonged reactions may adversely influence the release efficacy and intended therapeutic pathway. The lack of suitable in vitro platforms limits our ability to gain insight into the nature of immune responses at a single cell level. In order to establish an in vitro 3D system mimicking the connective host tissue counterpart, we utilized reproducible, compressed, rat-tail collagen polymerized matrices. THP1 cells (human acute monocytic leukaemia cells) differentiated into macrophage-like cells were chosen as cell model and their functionality was retained in the dense rat-tail collagen matrix. Placebo microparticles were later combined in the immune cell seeded system during collagen polymerization and secreted pro-inflammatory factors: TNFα and IL-8 were used as immune response readout (ELISA). Our data showed an elevated TNFα and IL-8 secretion by macrophage THP1 cells indicating that Placebo microparticles trigger certain immune cell responses under 3D in vivo like conditions. Furthermore, we have shown that the system is sensitive to measure the differences in THP1 macrophage pro-inflammatory responses to Active Pharmaceutical Ingredient (API) microparticles with different API release kinetics. We have successfully developed a tissue-like, advanced, in vitro system enabling selective "readouts" of specific responses of immune-related cells. Such system may provide the basis of an advanced toolbox enabling systemic evaluation and prediction of in vivo microparticle reactions on human immune-related cells.
authors.affiliation: Particles-Biology Interactions Laboratory, Swiss Federal Laboratories for Materials Science and Technology Empa, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Obarzanek-Fojt
authors.affiliation: Technical Research and Development, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Curdy
authors.affiliation: Technical Research and Development, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Loggia
authors.affiliation: Biointerface, Swiss Federal Laboratories for Materials Science and Technology Empa, Switzerland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lena
authors.affiliation: Biointerface, Swiss Federal Laboratories for Materials Science and Technology Empa, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grieder
authors.affiliation: Technical Research and Development, Novartis Pharma AG, Basel, Switzerland. Electronic address: malak.bitar@novartis.com.
authors.forename: Malak
authors.initials: M
authors.lastname: Bitar
authors.affiliation: Particles-Biology Interactions Laboratory, Swiss Federal Laboratories for Materials Science and Technology Empa, Switzerland. Electronic address: peter.wick@empa.ch.
authors.forename: Peter
authors.initials: P
authors.lastname: Wick
mesh_terms: D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000737:chemistry*; D004337:Drug Carriers; D006801:Humans; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D015203:Reproducibility of Results; D012212:Rheology
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: 3D cell culture; Collagen; Drug delivery; Immune response; PLGA microparticle; THP1