Serum Albumin Microcapsules Research Articles

Characterization of the mechanical properties of cross-linked serum albumin microcapsules: effect of size and protein concentration

A microfluidic technique is used to characterize the mechanical behavior of capsules that are produced in a two-step process: first, an emulsification step to form droplets, followed by a cross-linking step to encapsulate the droplets within a thin membrane composed of cross-linked proteins. The objective is to study the influence of the capsule size and protein concentration on the membrane mechanical properties. The microcapsules are fabricated by cross-linking of human serum albumin (HSA) with concentrations from 15 to 35 % (w/v). A wide range of capsule radii (∼40–450 μm) is obtained by varying the stirring speed in the emulsification step. For each stirring speed, a low threshold value in protein concentration is found, below which no coherent capsules could be produced. The smaller the stirring speed, the lower the concentration can be. Increasing the concentration from the threshold value and considering capsules of a given size, we show that the surface shear modulus of the membrane increases with the concentration following a sigmoidal curve. The increase in mechanical resistance reveals a higher degree of cross-linking in the membrane. Varying the stirring speed, we find that the surface shear modulus strongly increases with the capsule radius: its increase is two orders of magnitude larger than the increase in size for the capsules under consideration. It demonstrates that the cross-linking reaction is a function of the emulsion size distribution and that capsules produced in batch through emulsification processes inherently have a distribution in mechanical resistance.

Synthesis of multifunctional bovine serum albumin microcapsules by the sonochemical method for targeted drug delivery and controlled drug release

Multifunctional folic acid conjugated BSA@Fe3O4 microcapsules (FA-BSA@Fe3O4 MCs) have been prepared successfully based on the sonochemical method. The as-synthesized FA-BSA@Fe3O4 MCs have a suitable size range for biomedical applications, and a high loading capacity for water-insoluble drugs. Furthermore, FA-BSA@Fe3O4 MCs show excellent magnetic properties. Cytotoxicity tests indicate that FA-BSA@Fe3O4 MCs are non-toxic. Cellular uptake and flow cytometric assay illustrate together that FA-BSA@Fe3O4 MCs can target tumor cells selectively through molecular targeted endocytosis. As carriers for water-insoluble drugs, FA-BSA@Fe3O4 MCs are also proved to possess superior redox- and thermo- dual responsiveness for controlled drug release.

Effect of membranotropic and mucoadhesive formulations of protein proteinase inhibitors on bovine herpes virus-1 reproduction

The lipidized derivatives of Bowman–Birk soybean protease inhibitor (BBI) containing one to three oleoyl groups were synthesized and characterized. The (ole) 1- and (ole) 2BBI were demonstrated to have 200- and 100-fold higher uptake into Caco-2 cell monolayers compared to native BBI. The acylated BBI had increased affinity to elastase-like proteases. Aprotinin-loaded starch/bovine serum albumin microcapsules were prepared using interfacial cross-linking with terephthaloyl chloride and characterized for their morphology, size and release of the inhibitor. Various formulations of protein proteinase inhibitors were tested for their influence on BHV-1 reproduction in cell cultures. Native aprotinin possessed palpable dose-dependent effect inhibiting the virus reproduction up to 4.0 lg (10,000-fold). The bioadhesive, biodegradable aprotinin-loaded microcapsules were the most effective decreasing virus infectious titer up to 4.0 lg and delaying the cytopathic effect up to 144 h in lesser doses of aprotinin. The lipophilic derivative (ole) 1BBI was shown to exhibit effective inhibition (>100-fold) of BHV-1 reproduction unlike native BBI.

In vitro inhibition of bovine herpes virus 1 reproduction with native and microencapsulated proteinase inhibitor aprotinin

This study evaluated the antiviral effect of various dosage forms of proteinase inhibitor—aprotinin as a potential remedy for prophylactics and therapy of infectious bovine rhinotracheitis. Formulations of the inhibitor were tested for their influence on bovine herpes virus reproduction in cell cultures. Starch/bovine serum albumin microcapsules with aprotinin were prepared using interfacial cross-linking with terephthaloyl chloride and characterized for their morphology, size and release of the inhibitor. Two types of these microcapsules—impregnated and loaded with the inhibitor—were used in virus infectious studies. Native aprotinin possessed palpable dose-dependent antiviral effect inhibiting the virus reproduction up to 4.0 lg (10,000-fold) and delaying the cytopathic effect up to 96 h in the concentration 800–3300 TIU/ml. The bioadhesive, biodegradable aprotinin-loaded microcapsules were the most effective antiviral drug as this formulation allowed to decrease virus infectious titer up to 4.0 lg and a delay in the cytopathic effect of up to 144 h in lesser doses of inhibitor compared with the native form. In comparision the antiviral effect of microcapsules impregnated with aprotinin was not so appreciable. It was interesting to note that the results of the experiments on diverse cultures were very similar. This was because the drugs influenced the fundamental processes of virus replication cycle.

Sustained release of hydrophobic materials from sonochemically prepared bovine serum albumin microcapsules

Bovine serum albumin microcapsules containing chloroform have been synthesized from the mixture of bovine serum albumin solution and chloroform using an ultrasound irradiation technique. Sudan III dissolved in chloroform phase was microencapsulated. The membrane permeability of Sudan III was evaluated at 25, 30 and 37°C in chloroform. A lag phase was observed in the time course of the permeation. The length of the lag phase was temperature-dependent. It was found that the length of the lag phase was explained by the activation energy. The Arrhenius plot of the reciprocal of the lag time suggests that the existence of the lag phase is associated with activation energy. The activation energy was evaluated to be 60 kJ mol −1. The release of Sudan III from the microcapsules by the degradation of microcapsule membranes has also been studied.

Determination of free amino group content of serum albumin microcapsules: II. Effect of variations in reaction time and in terephthaloyl chloride concentration

Microcapsules were prepared through interfacial cross-linking of human serum albumin (HSA) using terephthaloyl chloride (TC) at a constant pH of 9.8. Variations were performed in reaction time (for a 2.5% w/v TC concentration) and in TC concentration (for a 30 min reaction time). Determination of free amino groups was performed on lyophilized microcapsules by means of a back titration method using trinitrobenzenesulfonic acid (TNBS). When prolonging the reaction time from 2 to 30 min. microcapsule-NH 2 content progressively decreased from 154 to 60 μmol/g dry weight. These results were in good agreement with those of a previous study conducted using Fourier transform infrared spectroscopy. A slight recovery of free-NH 2 was observed after 60 and 120 min. Increasing TC concentration from 1 to 5% (w/v) resulted in a progressive decrease in microcapsule-NH 2 content from 99 to 38 μmol/g.

Polyhydroxamic serum albumin microcapsules: preparation and chelating properties

Polyhydroxamic serum albumin microcapsules were prepared through interfacial cross-linking with terephthaloyl chloride and further treatment of microcapsules with alkaline hydroxylamine. They exhibited iron-binding properties which were increased by esterification of the free carboxylic groups of the membrane with benzylic alcohol using a carbodiimide, prior to the hydroxylamine treatment.