Application of erythrocytes, the most abundant cells of the human body with desirable physiologic and morphologic characteristics, in drug delivery has been exploited extensively. These cellular carriers, having remarkable biocompatibility, biodegradability, and life-span in circulation, can be loaded by a wide spectrum of compounds of therapeutic value using different chemically, as well as physically, based methods. Most of the characteristics of the erythrocytes, including shape, membrane fragility, deformability, and hematologic indices undergo some degree of irreversible changes during the loading procedure. The efflux pattern of the encapsulated compounds from the carrier erythrocytes covers a wide range between a relatively rapid release (complete release within a few hours) and no detectable release until the cell lysis. A series of methods have been tested successfully for improvement of in vitro storability of the carrier erythrocytes without any significant changes in cell biology as well as drug delivery efficacy. Carrier erythrocytes have been exploited for several potential applications, including intravenous slow release of therapeutic agents, enzyme therapy, drug targeting to reticuloendothelial system (RES), improvement of oxygen delivery to tissues, and preparation of fused cells.
In vitro characteristics of the human erythrocytes loaded by enalaprilat have been evaluated. Erythrocytes obtained from a healthy volunteer were loaded by enalaprilat using the hypotonic preswelling method, and the loading parameters, drug-release kinetics, hematological indices, particle size distribution, scanning electron microscopy view, osmotic and turbulence fragilities, and deformability of the resulting carrier cells were determined along with the sham encapsulated and unloaded cells. Carrier erythrocytes, having acceptable loading parameters, released their drug content according to zero-order kinetics. Mean corpuscular hemoglobin and mean corpuscular hemoglobin content values of the cells decreased, particle size dispersion increased, the cells transformed to cup-form, the erythrocytes became more fragile against osmotic pressure and turbulent flow, and, finally, the deformability of the cells decreased significantly upon drug loading.
Multiple phase emulsions are increasingly used as alternatives to simple emulsions in personal care products. One of the major advantages of these emulsions over simple emulsions is slow and controlled release of their ingredients. Other favorite cosmetic characteristics of multiple emulsions include occlusivity (in O/W/O emulsions), esthetics and consumer acceptance. Vitamin C (ascorbic acid) has been widely used in formulations of skin care products. Due to its effects on collagen biosynthesis, it is considered as moisturizing and anti-aging active ingredient. Instability problems such as oxidation susceptibility have made incorporating vitamin C in topical formulations a challenging issue. The O/W/O emulsions have been formulated using two-step procedure, to investigate vitamin C stability and its release profile. By using different surfactant types and ratios, volume ratio of phases, multiple emulsions containing vitamin C were prepared. Different parameters and formulation factors such as temperature of phases, duration and speed of mixing were evaluated. Based on our results, more stable emulsions were prepared from non-ionic siliconized surfactants, sorbitan derivatives and co-surfactants such as polyglyceryl derivatives. Physical stability was determined by microscopic examination, centrifugation and incubating emulsions in different temperatures. Vitamin C in vitro release studies from O/W and O/W/O emulsions were conducted using Franz diffusion cell (at room temperature) and UV spectrophotometry. The results showed that in the first four-hour period, about 14% of vitamin C released from O/W/O emulsions. It appears that in multiple emulsions the profile of release follows zero-order kinetics. Our data indicate that incorporating vitamin C in multiple emulsions significantly increased its stability possibly attributed to the formation of reverse micelles of surfactants (and/or co-surfactants), which entrapped vitamin C inside the micelles surrounded by hydrophilic heads of surfactant. Moreover, vitamin C was released from multiple emulsions in a zero order slow and controlled release manner.
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