ABSTRACT
A new aqueous nanoparticle system has been developed using complex coacervation employing the oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with zinc sulfate as a stabilizing agent. Amphotericin B (AmB) was loaded into the nanoparticles as a model drug. The nanoparticles contained PEI and DS in the weight ratio of approximately 1:2. They possessed a zeta potential of approximately +30 mV and demonstrated a narrow size distribution in the range 100-600 nm with a polydispersity index of 0.2. Electron microscopy revealed spherical nanocapsules with a smooth surface. Very favorable drug entrapment and recovery efficiencies of up to 85% were routinely observed. Processing parameters, such as the pH of the PEI solutions, ratio of the two polymers, as well as the concentrations of DS and zinc sulfate, all played a significant role in controlling particle size. Dissolution studies demonstrated a fast release that is dependent on the model drug solubility. The AmB-loaded nanoparticles displayed no toxicity in tissue culture in contrast to free drug and were almost as efficacious as free drug in killing Candida albicans. Advantages of this simple technique are (1) ease of manufacturing and mild preparation conditions, (2) employment of completely aqueous processing conditions, (3) use of biocompatible polymers that can be prepared aseptically, (4) ability to control their size, and (5) a high level of drug entrapment.
Subject(s)
Amphotericin B/administration & dosage , Dextran Sulfate/administration & dosage , Polyethyleneimine/administration & dosage , Amphotericin B/chemistry , Amphotericin B/toxicity , Chemistry, Pharmaceutical , Hydrogen-Ion Concentration , Particle Size , Solubility , Spectroscopy, Fourier Transform InfraredABSTRACT
We report a solid-phase iodine- 125 radioimmunoassay for serum cortisol in which the interfering binding proteins are inactivated by a combination of reaction pH and 8-anilino-1-naphthalenesulfonic acid. The procedure is easy to perform and gives accurate and reliable results. The shift in pH for optimum binding of an antibody resulting from immobilization on a solid support, used to decrease cortisol binding competition in the present test, is potentially exploitable in other antibody and enzyme systems.