Modeling Drug Discovery in an Undergraduate Laboratory by the pH- and Trypsin-Triggered Release of Malachite Green by Skim Milk-Coated Calcium Citrate and Calcium Carbonate Microparticles

A new undergraduate laboratory introduces undergraduate students to nanotechnology-based targeted drug design, aiding their preparation to medical-oriented careers. Specifically, it demonstrates pH- and enzyme-triggered targeted drug release minimizing patient’s exposure to the drug. The students synthesize calcium carbonate microparticles (CCMPs) or calcium citrate nanosponge (CCNS) as drug carriers and explore casein or skim milk as a gatekeeping element, malachite green (MG) as a drug, and trypsin or pH 5.5 as drug release triggers. When the loaded CCMPs (or CCNS) are introduced to an environmental trigger, the casein is degraded or the calcium salt core is dissolved. In either case, the drug is released. The students discover that the drug release and drug retention properties depend on the core material of the carrier and the gatekeeping element (casein or skim milk). The further finding that the fat content of the milk hinders the drug release process by the particles with the milk-sourced casein demonstrates fine-tuning of a drug formulation. The diluted skim milk coating blocks drug release in the neutral environment (7.4 pH) better than the lab grade 0.1% casein does, which prompts students to come up with a hypothesis. The laboratory introduces students to cutting-edge nanotechnology and models a real drug discovery process.