Formulation, Characterization, and Cytotoxic Effect of Indomethacin-Loaded Nanoparticles

Abstract

Background: Indomethacin (IND), classified as class 2 in the Biopharmaceutical Classification System (BCS), has emerged as an anti-inflammatory agent with low solubility and high permeability. Widely used in the treatment of various diseases, such as rheumatoid arthritis and ankylosing spondylitis, this drug is well-known for its adverse effects, particularly in the stomach, and a short biological half-life, which is around 1.5-2 hours.

Objective: The aim of this study was to overcome the challenges of low solubility, short half-life, and serious side effects occurring with the use of IND-loaded formulations of Solid Lipid Nanoparticles (SLNs) and Polymeric Nanoparticles (PNPs).

Methods: For PNPs, emulsification/solvent evoporation method was employed, and for SLNs, the hot homogenizaton method was applied. Eudragit® RLPO (RLPO) and Eudragit® RSPO (RSPO) were used as polymers for PNP and Dynasan®116 (DYN) was used as the solid lipid for SLN. Prepared formulations were characterized for Particle Size (PS), Poly-dispersity Index (PDI), Zeta Potential (ZP), Encapsulation Efficiency (%EE), and drug-ex-recipient compatibility using DSC, FT-IR, and 1H NMR; cumulative drug release rates were assessed using HPLC and in vitro cytotoxicities were examined by the MTT assay.

Results: Both PNP and SLN formulations’ zeta potential, particle size, and PDI results indicated the formulations to have good stability. Encapsulation efficiency values were obtained as desired. Drug-excipient compatibility was proved using DSC, FT-IR, and 1H NMR. In vitro dissolution results have proven both formulations to have longer release than pure indomethacin. In the MTT analysis of indomethacin application for 24 and 48 hours, a linear correlation was observed between drug concentration and cell viability, and it was determined that the PNP formulation exhibited fewer toxic effects among the formulations. This has proven the PNP nanocarrier as safer for normal cells.

Conclusion: IND-loaded PNP and SLN formulations have been successfully prepared in this work and they have achieved drug release in the intestine and prolonged the release duration.