First batch of scientific papers; Insulin Particle Formation

[This post will be edited as I read.]

So, I am going to try to work my way through the 4 papers I have been sent so far by my summer internship. Now, I should be writing essays so I can finish the term, but I'm not having any luck. At least this is more productive than watching tv.
I will give the abstract and journal for each of these papers (one here, then more posts), and then I will be adding definitions to terms that I had to look up, plus my summary of each part of the paper. These are my notes, so that I have a working base of knowledge when I read more papers in the future, but maybe they will be of use to someone.

Insulin Particle Formation in Supersaturated Aqueous Solutions of Poly(Ethylene Glycol)

Lev Bromberg, Julia Rashba-Step and Terrence Scott

Epic Therapeutics, Inc., Norwood, Massachusetts 02062

Biophysical Journal, Volume 89, Issue 5, 3424-3433, 1 November 2005

Abstract

Protein microspheres are of particular utility in the field of drug delivery. A novel, completely aqueous, process of microsphere fabrication has been devised based on controlled phase separation of protein from water-soluble polymers such as polyethylene glycols. The fabrication process results in the formation of spherical microparticles with narrow particle size distributions. Cooling of preheated human insulin-poly(ethylene glycol)-water solutions results in the facile formation of insulin particles. To map out the supersaturation conditions conducive to particle nucleation and growth, we determined the temperature- and concentration-dependent boundaries of an equilibrium liquid-solid phase separation. The kinetics of formation of microspheres were followed by dynamic and continuous-angle static light scattering techniques. The presence of PEG at a pH that was close to the protein’s isoelectric point resulted in rapid nucleation and growth. The time elapsed from the moment of creation of a supersaturated solution and the detection of a solid phase in the system (the induction period, t_ind) ranged from tens to several hundreds of seconds. The dependence of t_ind on supersaturation could be described within the framework of classical nucleation theory, with the time needed for the formation of a critical nucleus (size <10nm) being much longer than the time of the onset of particle growth. The growth was limited by cluster diffusion kinetics. The interfacial energies of the insulin particles were determined to be 3.2–3.4 and 2.2mJ/m² at equilibrium temperatures of 25 and 37°C, respectively. The insulin particles formed as a result of the process were monodisperse and uniformly spherical, in clear distinction to previously reported processes of microcrystalline insulin particle formation.

phase separation:
a protein's isoelectric point:
nucleation:
classical nucleation theory:
cluster diffusion kinetics:
interfacial energy:
monodisperse: