By: Lipika Chablani
Recently, the labs of Liangfang Zhang, Ph.D., and Joesph Wang, Ph.D., published some very exciting work about their “micromotor” based novel drug delivery systems. Their published article from Angewandte Chemie shares the formulation and applications of these that can neutralize gastric acid and successfully deliver the drug through the stomach.
Oral drug delivery is often challenged by the low gastric pH and the transit time the drug delivery system spends in that acidic pH. Harsh gastric pH can denature protein/peptide based therapeutics and can also impact the absorption profiles of small molecule therapeutics, resulting in reduced efficacy. To alleviate this situation, often the therapeutic medications are accompanied with proton pump inhibitors to neutralize the gastric pH. However, long term use of such proton pump inhibitors yields several adverse effects, such as hypochlorhydria and hypergastrinemia, that can be an additional challenge clinically. There are several studies geared in this direction to resolve the over-consumption of proton pump inhibitors and yet provide a suitable gastric environment for drug delivery.
Maintaining the desired pH for drug delivery and absorption from the stomach has been a challenge and with the concerns associated with long-term use of proton pump inhibitors, an alternative mode to neutralize gastric pH will be beneficial. Poor gastric absorption or drug degradation in the gastric lumen often impacts its pharmacokinetic profile of the molecule. This is then translated to altered therapeutic benefits, gastric reflux in the patients and increased number of visits at the physician’s office. The above-mentioned study proposes the use of unique “micromotors” to manage this problem. These micromotors are composed of magnesium-based motors, the drug payload, and a pH sensitive polymer coating of Eudragit L100-55. These microdevices function by using gastric acid as a fuel, and thus it depletes the proton concentration in the stomach. As the consumption of gastric acid fuels the micromotors, they get propelled further into the stomach and exhaust the available protons. The propulsion stirs the gastric fluid and provides a uniform milieu for drug absorption.
The authors report, after the consumption of the micromotors, the pH rapidly neutralizes from 1.3 to 6.2 in 12 minutes and stabilizes to 7.5 after 18 minutes! Overall, in less than 20 minutes the gastric pH is neutralized and the drug payload begins to release via the dissolution of pH responsive polymer. This neutralization effect lasts for 24 hours and the gastric pH restores to normal beyond that point. The system is biocompatible for human applications as magnesium is an essential dietary mineral and Eudragit L100-55 has previously been safely used for oral drug delivery applications. These modified drug delivery systems have been studied both in vitro and in vivo and have been evaluated for their efficacy and safety profiles.
The results are promising and certainly guides us further for successful neutralization of gastric pH in a rapid, efficient, and safe manner. It will be exciting to see the next phase of these studies as they get evaluated in higher species.