Macropored microparticles with a core–shell architecture for oral delivery of biopharmaceuticals

Abstract

Microparticles (MPs) have been extensively researched as a potential drug delivery vehicle. Here, we investigated the fabrication of MPs with pH-responsive macropores and evaluated their potential applicability in developing solid oral drug formulations. Our previous study showed that macropored MPs, made of Eudragit L100-55, could encapsulate 100 nm, 1 µm, and 4 µm sized fluorescent beads-model drugs that are mimicking vaccines, bacteria, and cells. In the present study, closed-pored MPs after freeze-drying were coated with a gastric soluble Eudragit EPO layer to protect MPs in the simulated pregastric environment. Subsequently, drug encapsulated MPs maintained their intact closed-pored structure in the simulated gastric environment and exhibited a rapid release in the simulated intestine environment. Our MP system was found to provide a significantly higher level of protection to the encapsulated lactase enzyme compared to the control sample (i.e. without using MPs). Real-time fluorescence microscopy analysis showed that macropored MPs released encapsulated drugs in a burst-release pattern and in a size-independent manner. This work shows that our proposed EPO-coated MPs with pH-responsive macropores can meet the challenges posed by the multiple physiological environments of the digestive tract and be used in developing highly effective solid oral drug/vaccine formulations.

Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals

“…These methods could hardly be successful due to the complications associated with diffusional material flow through the solid state polymeric shells. Since the drug can be loaded only by soaking the particles in a concentrated solution of drug, this method does not yield satisfactory levels of loading efficiency, limiting its general application [186,189,190].…”

Microfabricated Probiotic Formulation for Inhibition of Salmonella

“…Importantly, it should be noted that the organic solvent composition is a critical factor in determining the extent of solubility of the polymer and compatibility with the microfabrication of the probiotic formulations. In this work, we used the cosolvent, composed of dichloromethane:ethanol:isopropyl alcohol in a 2:1:1 ratio, that has previously been used for the fabrication of pH-responsive macro-pored microparticles using microemulsion technology. − It was found that the increase in the composition of dichloromethane makes it difficult to spray-coat the polymer due to rapid solvent evaporation and poor adhesion between the polymer coating and trehalose. On the other hand, an increase in the composition of more polar solvents can dissolve trehalose and damage encapsulated cells.…”

Effects of cell line proliferation on the aggregation and stability of a hyaluronic acid solution (HA)/PLGA microparticles dispersed in the culture system

“…The interaction between P LGA MPs and the cell membrane is a dynamic process regulated by nonspecific and weak bonds, such as electrostatic interactions and hydrogen bonding. It is known that modification of the MPs surface charge can improve their localization at the action site and then the interaction with specific cellular targets [8,12,15] . Despite the remarkable progresses in the field of P LGA MPs, the exploration of cellular response to MPs remains an attractive goal to optimize their therapeutic possibilities.…”