title: Development of biodegradable methylprednisolone microparticles for treatment of articular pathology using a spray-drying technique.
abstract: In this work, microparticles were prepared by spray-drying using albumin, chondroitin sulfate, and hyaluronic acid as excipients to create a controlled-release methylprednisolone system for use in inflammatory disorders such as arthritis. Scanning electron microscopy demonstrated that these microparticles were almost spherical, with development of surface wrinkling as the methylprednisolone load in the formulation was increased. The methylprednisolone load also had a direct influence on the mean diameter and zeta potential of the microparticles. Interactions between formulation excipients and the active drug were evaluated by x-ray diffraction, differential scanning calorimetry, and thermal gravimetric analysis, showing limited amounts of methylprednisolone in a crystalline state in the loaded microparticles. The encapsulation efficiency of methylprednisolone was approximately 89% in all formulations. The rate of methylprednisolone release from the microparticles depended on the initial drug load in the formulation. In vitro cytotoxic evaluation using THP-1 cells showed that none of the formulations prepared triggered an inflammatory response on release of interleukin-1β, nor did they affect cellular viability, except for the 9.1% methylprednisolone formulation, which was the maximum test concentration used. The microparticles developed in this study have characteristics amenable to a therapeutic role in inflammatory pathology, such as arthritis.
authors.affiliation: Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile.
authors.forename: Blanca
authors.initials: B
authors.lastname: Tobar-Grande
authors.forename: Ricardo
authors.initials: R
authors.lastname: Godoy
authors.forename: Paulina
authors.initials: P
authors.lastname: Bustos
authors.forename: Carlos
authors.initials: C
authors.lastname: von Plessing
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.forename: Claudia
authors.initials: C
authors.lastname: Olave
authors.forename: Carolina
authors.initials: C
authors.lastname: Gómez-Gaete
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002809:Chondroitin Sulfates / Q000737:chemistry; D003890:Desiccation / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D053583:Interleukin-1beta / Q000032:analysis; D008775:Methylprednisolone / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D053583:Interleukin-1beta; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D008775:Methylprednisolone
keywords: chondroitin sulfate; cytotoxic assays; hyaluronic acid; methylprednisolone; microparticles; spray-drying