ABSTRACT
Indomethacin is a non-steroidal anti-inflammatory agent included in one of the most commonly used drug classes worldwide. The use of this drug results in certain side effects, including gastrointestinal complications. Therefore, there exists a need to develop better methods for the delivery of such drugs into the body, such as those employing nanoparticles. The aim of the present study was to evaluate the cytotoxic and genotoxic effects of indomethacin-loaded Eudragit(®) L 100 nanocapsules (NI; based on methacrylic acid and methyl methacrylate) on cells unable (lymphocytes) and able to metabolize drugs (HepG2 cells), using comet and cytokinesis-block micronucleus (CBMN) assays in vitro. Cells were exposed to NI at concentrations of 5, 10, 50, 125, 250, and 500 µg/mL. The comet assay showed that NI induced no significant DNA damage in either cell type at any of the concentrations tested. The CBMN test confirmed these results; however, the highest concentration of 500 µg/mL resulted in a small but statistically significant clastogenic/aneugenic effect in HepG2 cells. These findings should encourage the development of new investigations of this nanomaterial as a delivery vehicle for anti-inflammatory drugs, such as indomethacin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Excipients/toxicity , Indomethacin/toxicity , Methacrylates/toxicity , Nanocapsules/toxicity , Polymers/toxicity , Adolescent , Adult , Cell Survival/drug effects , DNA Damage , Drug Evaluation, Preclinical , Female , Hep G2 Cells , Humans , Lymphocytes/drug effects , Lymphocytes/physiology , Male , Young AdultABSTRACT
In this preliminary work, an enteric polymer has been used for encapsulating bovine serum albumine (BSA) as a model protein drug. Poly (lactide-co- glycolide) has been commonly used for oral administration purposes as a polymer matrix, but in this case an enteric polymer was used effectively to protect the protein in a gastric environment. A modified water/oil/water technique was used to decrease the particle diameter, and transmission electron microscopy experiments showed that the average diameter of the nanoparticles obtained was below 100 nm. The spherical nature of the particles and their diameters strongly depend on the control of the process parameters. The encapsulation efficiency was 77% for sample B4, and protein release profiles for both samples B3 and B4 indicate that these systems possess controlled-release characteristics. Finally, as a result of electrophoresis (SDS-PAGE), the BSA was not chemically affected under encapsulation conditions.
