Determination of P‐glycoprotein inhibition by excipients and their combinations using an integrated high‐throughput process

Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation, Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

“…The effective inhibition of the P-gp efflux pumps is being considered as a potential strategy to improve the brain bioavailability of CNS-active drugs. Previous studies have showed that certain chemical components including PEG derivatives, used as surfactants or surface-coating materials, have the tendency to inhibit P-gp efflux pumps through several mechanisms (14,34,35). Figure 6 shows the P-gp ATPase activity of breviscapine and the different surfactants used in the SLN formulations as compared with the basal-and verapamil-stimulated P-gp ATPase activity.…”

“…We therefore suggest that the uptake of the breviscapineloaded SLNs across the BBB was facilitated by the synergistic inhibitory action of PEG derivatives used as the surface modifier for the SLNs on the P-gp efflux pumps. In a previous study to determine the ability of different excipients to inhibit P-gp efflux pumps, Wang et al (14) demonstrated that among the excipients tested, PEG stearates with a moderate PEG length (20 to 50) consistently showed better inhibition of P-gp activity than other PEG derivatives investigated. They also found in their studies that nonionic PEG-poly(propylene oxide) copolymers and PEG of any length did not inhibit P-gp at the concentrations tested.…”

“…Previous researches had shown that a few common, nontoxic, and generally recognized as safe PEG derivatives that are used in drug formulations have an inhibitory effect on P-gp efflux pump, which are very much actively involved in restricting the penetration of drugs into the brain (14,15). Evaluation of brain drug concentrations in living and freely moving animals by in vivo cerebral microdialysis (MD) has also been shown to be an objective method of accessing the ECF concentration of drugs that cross the BBB (16).…”

Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs

“…Unlike PEG 400, there is a lack of information regarding the potential interactions between PEG 4000 and P-gp transporter, although reports are available with respect to other PEG grades or derivatives (37)(38)(39). For example, the efflux transport of rhodamine 123 (a P-gp substrate) was found to be significantly decreased when incubated with PEG 400, 2,000, and 20,000 in Caco-2 cell lines (37).…”

Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges

“…Many excipients often used in pharmaceutical formulations have been reported to have inhibitory effects on P-glycoprotein, an important membrane-associated transport protein (Wang et al, 2004). Because inhibition of efflux transporters can have an effect on drug bioavailability, identification of these excipients and their extent of inhibition are therefore important for pharmaceutical development.…”