Nanostructured Lipid Carriers for Oral Delivery of a Corticosteroid: Role of Formulation on Biopharmaceutical Performance

Corticosteroids are potent anti-inflammatory and immunosuppressive drugs widely used world-wide for treatment of diverse conditions. However, their use is restricted by their poor bioavailability and high riskbenefit ratio. Therefore, the aim of this study was to develop nanostructred lipid carriers (NLC) of prednisolone acetate (PA) to improve the drug's therapeutic outcome by altering its pharmacokinetic profile and/or allow preferential targeting to inflammatory tissues. PA-loaded NLCs were formulated by solvent injection method using Compritol (solid lipid), oleic acid (liquid lipid) and Tween 80 or Pluronic F68 (surfactant). Formulation conditions, such as liquid lipid concentration, total lipids, drug:lipid ratio and surfactant type were optimized based on particle size (PS), polydispersity index (PDI), and encapsulation efficiency (EE%) results. Optimized formulation was further characterized for its surface morphology, thermal properties, storage stability and anti-inflammatory activity in an animal acute inflammation model. Selected NLCs displayed PS of 170.7 nm, EE% of 67.4%, sustained release over 72 h and good stability for 30 days at refrigeration conditions. PA NLCs displayed superior anti-inflammatory activity of 83.9 +/- 4.46% compared to PA suspension (40.5 +/- 7.03%) and drug-free NLCs (54.7 +/- 6.12%). The current work delineates the potential of NLCs for distinctly improved biopharmaceutical performance of PA. (c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.