ABSTRACT
PURPOSE: In an effort to expand the application of core-shell structures fabricated by electrostatic layer-by-layer (LbL) self-assembling for drug delivery, this study reports the controlled release of dexamethasone from microcrystals encapsulated with a polyelectrolyte shell. METHODS: The LbL self-assembly process was used to produce dexamethasone particles encapsulated with up to five double layers formed by alternating the adsorption of positively charged poly(dimethyldiallyl ammonium chloride), negatively charged sodium poly(styrenesulfonate) and depending on the pH positively or negatively charged gelatin A or B onto the surface of the negatively charged dexamethasone particles. The nano-thin shells were characterized by quartz crystal microbalance measurements, microelectrophoresis, microcalorimetry, confocal microscopy, and scanning electron microscopy. In vitro release of dexamethasone from the microcapsules suspended in water or carboxymethylcellulose gels were measured using vertical Franz-type diffusion cells. RESULTS: Sonication of a suspension of negatively charged dexamethasone microcrystals in a solution of PDDA not only reduced aggregation but also reduced the size of the sub-micrometer particles. Assembly of multiple polyelectrolyte layers around these monodispersed cores produced a polyelectrolyte multilayer shell around the drug microcrystals that allowed for controlled release depending on the composition and the number of layers. CONCLUSIONS: Direct surface modification of dexamethasone microcrystals via the LbL process produced monodispersed suspensions with diffusion-controlled sustained drug release via the polyelectrolyte multilayer shell.
Subject(s)
Cell Survival/drug effects , Delayed-Action Preparations/pharmacokinetics , Dexamethasone/pharmacokinetics , Microspheres , Particle Size , Capsules/analysis , Capsules/chemistry , Cell Aggregation , Chemistry, Pharmaceutical/methods , Crystallization , Delayed-Action Preparations/administration & dosage , Dexamethasone/administration & dosage , Dexamethasone/analysis , Diazonium Compounds/analysis , Electrolytes/analysis , Electrolytes/chemistry , Hot Temperature , Nanotechnology/methods , Polymers/analysis , Polymers/chemistry , Powders/analysis , Powders/chemistry , Pyridines/analysis , Sonication , Static Electricity , Technology, Pharmaceutical/methodsABSTRACT
A highly-interdisciplinary approach has been developed for minimizing the immunogenicity of films, coatings, microcapsules and other nano-structured materials fabricated from designed polypeptide chains. It is to base the amino-acid sequences on solvent-exposed regions in the folded states of proteins from the same organism. Each such region that meets defined criteria with respect to charge is called a sequence motif. The approach becomes more specifically tailored for intravenous applications by requiring an employed sequence motif to correspond to a known blood protein. An algorithm has been developed to identify sequence motifs in protein-encoding regions of a genome. This work is focused on sequence motifs of charge per unit length >0.5 at neutral pH. It has been found that the number of unique sequence motifs meeting this criterion in available human genome data is maximal for motifs of approx. 7 residues in length. We have designed polypeptides on the basis of computational analysis and shown that they can be used to fabricate nano-structured thin films by electrostatic layer-by-layer assembly (ELBL). The results of this work are discussed with a view to possible applications in biotechnology, notably development of biocompatible coatings and microcapsules.
