Human serum albumin (HSA) nanoparticles: Reproducibility of preparation process and kinetics of enzymatic degradation

Nanoparticles prepared from human serum albumin (HSA) are versatile carrier systems for drug delivery and can be prepared by an established desolvation process. A reproducible process with a low batch-to-batch variability is required for transfer from the lab to an industrial production. In the pres...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of pharmaceutics Vol. 347; no. 1; pp. 109 - 117
Main Authors:	Langer, K., Anhorn, M.G., Steinhauser, I., Dreis, S., Celebi, D., Schrickel, N., Faust, S., Vogel, V.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 22-01-2008 Elsevier
Subjects:	Biological and medical sciences Cathepsin B - chemistry Drug Compounding - methods Enzymatic degradation General pharmacology Glutaral - chemistry Human serum albumin (HSA) Humans Hydrogen-Ion Concentration Kinetics Medical sciences Molecular Weight Nanoparticles Nanoparticles - chemistry Particle Size Pepsin A - chemistry Peptide Hydrolases - chemistry Peptide Hydrolases - metabolism Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Recombinant human serum albumin (rHSA) Recombinant Proteins - chemistry Recombinant Proteins - metabolism Reproducibility of Results Serum Albumin - chemistry Serum Albumin - genetics Serum Albumin - metabolism Static Electricity Surface Properties Trypsin - chemistry Nanoparticles Recombinant human serum albumin (rHSA) Particle size Enzymatic degradation Human serum albumin (HSA) Human Pharmaceutical technology Nanoparticle Process Serum albumin Degradation Reproducibility Preparation Microparticle Kinetics
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Nanoparticles prepared from human serum albumin (HSA) are versatile carrier systems for drug delivery and can be prepared by an established desolvation process. A reproducible process with a low batch-to-batch variability is required for transfer from the lab to an industrial production. In the present study the batch-to-batch variability of the starting material HSA on the preparation of nanoparticles was investigated. HSA can build dimers and higher aggregates because of a free thiol group present in the molecule. Therefore, the quality of different HSA batches was analysed by size exclusion chromatography (SEC) and analytical ultracentrifugation (AUC). The amount of dimerised HSA detected by SEC did not affect particle preparation. Higher aggregates of the protein detected in two batches by AUC disturbed nanoparticle formation at pH values below 8.0. At pH 8.0 and above monodisperse particles between 200 and 300 nm could be prepared with all batches, with higher pH values leading to smaller particles. Besides human derived albumin a particle preparation was also feasible based on recombinant human serum albumin (rHSA). Under comparable preparation conditions monodisperse nanoparticles could be achieved and the same effects of protein aggregates on particle formation were observed. For nanoparticulate drug delivery systems the enzymatic degradation is a crucial parameter for the release of an embedded drug. For this reason, besides the particle preparation process, particle degradation in the presence of different enzymes was studied. Under acidic conditions HSA as well as rHSA nanoparticles could be digested by pepsin and cathepsin B. At neutral pH trypsin, proteinase K, and protease were suitable for particle degradation. It could be shown that the kinetics of particle degradation was dependent on the degree of particle stabilisation. Therefore, the degree of particle stabilisation will influence drug release after cellular accumulation of HSA nanoparticles.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0378-5173 1873-3476
DOI:	10.1016/j.ijpharm.2007.06.028