A Prospective Analysis of Co-Processed Non-Ionic Surfactants in Enhancing Permeability of a Model Hydrophilic Drug

Abstract

Paracellular route is a natural pathway for the transport of many hydrophilic drugs and macromolecules. The purpose of this study was to prospectively evaluate the ability of novel co-processed non-ionic surfactants to enhance the paracellular permeability of a model hydrophilic drug metformin using Caco-2 (human colonic adenocarcinoma) cell model. A three-tier screen was undertaken to evaluate the co-processed blends based on cytotoxicity, cellular integrity, and permeability coefficient. The relative contribution of the paracellular and the transcellular route in overall transport of metformin by co-processed blends was determined. Immunocytochemistry was conducted to determine the distribution of tight-junction protein claudin-1 after incubation with the co-processed blends. It was found that novel blends of Labrasol and Transcutol-P enhanced metformin permeability by approximately twofold with transient reduction in the transepithelia electrical resistance (TEER) and minimal cytotoxicity compared with the control, with the paracellular pathway as the major route of metformin transport. Maximum permeability of metformin (∼10-fold) was mediated by Tween-20 blends along with >75% reduction in the TEER which was irreversible over 24-h period. A shift in metformin transport from the paracellular to the transcellular route was observed with some Tween-20 blends. Immunocytochemical analysis revealed rearrangement of the cellular borders and fragmentation on treatment with Tween-20 blends. In conclusion, cytotoxicity, cellular integrity, and permeability of the hydrophilic drugs can be greatly influenced by the polyoxyethylene residues and medium chain fatty acids in the non-ionic surfactants at clinically relevant concentrations and therefore should be thoroughly investigated prior to their inclusion in formulations.

Potential Herb-Drug Pharmacokinetic Interactions between African Wild Olive Leaf Extract and Selected Antihypertensive Drugs

“…The TEER results confirmed the intactness of the monolayers prior to the commencement of the transport experiments (all cell monolayers exhibited TEER > 250 Ω). There was, however, a decrease in the TEER values upon the application of test compounds to the cells, which may be an indication of temporary tight junction changes [19] due to the change in environment. The TEER values are shown in ▶ Table 2.…”

Nanoemulsion Stabilized by Safe Surfactin from Bacillus subtilis as a Multifunctional, Custom-Designed Smart Delivery System

“…In the case of human psoriatic dermal fibroblasts, 0.5 mM TR still had an antiproliferative effect, while for human normal dermal fibroblasts 0.1 mM and 0.01 mM concentrations were poorly effective [ 48 ]. In the study conducted by Alvi and Chaterjee, TR showed an IC 50 value of 2.0 ± 0.35% ( v/v ) when tested against Caco-2, while Labrasol (another non-ionic surfactant) was much more toxic (IC 50 0.22 ± 0.01%) to this line [ 49 ].…”

Overview of Transporters in Pharmacokinetics and Drug Discovery

“…If the Caco‐2 monolayer is disrupted, the lucifer yellow will leak into the basolateral compartment. With a MW approximately 457 g/mol, lucifer yellow is a relatively small molecule that is used as a marker of paracellular transport since it cannot pass across the cellular membrane (Alvi & Chatterjee, ).…”