The microenvironment -controlled encapsulation (MiCE) process for drug delivery

Connie Susan Snider, Purdue University

Abstract

Microencapsulation is a technique that can bring about in vivo controlled drug release through the formation of a rate-controlling biodegradable polymer matrix around the drug contents. This polymer matrix also serves a barrier, which can protect fragile protein drugs from in vivo enzymatic degradation. By parenterally administering microencapsulated protein and peptide therapeutics, patients can maintain adequate blood levels of active for weeks or even months, thereby diminishing patient discomfort and increasing compliance. However, protein microencapsulation, using current industrial methods, can expose protein to denaturing conditions, including organic/aqueous interfaces, organic solvents, shear stress, and high temperatures. To meet these challenges, we have developed a new microencapsulation technology, termed the Microenvironment- Controlled Encapsulation (MiCE) Process, which exposes protein to minimal amounts of chemical and mechanical stress and gives the operator precise control over the microenvironment in which the microcapsules are produced. The primary component in this system is a flow cytometer nozzle that hydrodynamically focuses an inner drug and outer polymer solution emanating from a coaxial needle assembly into a two-layer compound jet. This compound jet is segmented in a 250 μm quartz microchannel by Rayleigh-type instability within a co-flowing aqueous sheath. Since the polymer solution is comprised of poly(lactic-co-glycolic acid) (PLGA) dissolved in a water miscible organic solvent, most of the interfacial phase separation is rapidly induced at the boundary between the PLGA solution and sheath, leading to the production of reservoir-type microcapsules. By controlling the driving pressures of each component solution and the PLGA solution viscosity, we were able to modify the core size, PLGA film thickness, and microcapsule size. Using this technology, we produced microcapsules containing lysozyme as a model protein drug with mean diameters ranging from 15–25 μm, an easily injectable size range. In addition to protein stabilization and effective control over the microcapsule properties, the MiCE Process allows the operator to easily produce a large quantity of microcapsules within a short period of time in a continuous manner, making it a promising commercial microencapsulation system.

Degree

Ph.D.

Advisors

Park, Purdue University.

Subject Area

Pharmacology

COinS