Abstract
Several variants of hybrid polyelectrolyte microcapsules (hPEMC) were designed and produced by modifying in situ gelation methods and layer-by-layer (LbL) techniques. All of the hPEMC designs tested in the study demonstrated high efficiency of the model hydrophilic compound loading into the carrier cavity. In addition, the microcarriers were characterized by high efficiency of incorporating the model hydrophobic compound rhodamine B isothiocyanate (RBITC) into the hydrophobic layer consisting of poly-(d,l)-lactide-co-glycolide (PLGA), oligo-(l)-lactide (OLL), oligo-(d)-lactide (OLD) and chitosan/gelatin/poly-l-lactide copolymer (CGP). The obtained microcapsules exhibited high storage stability regardless of the composition and thickness of the polyelectrolyte shell. Study of the impact of hybrid polyelectrolyte microcapsules on viability of the adhesive L929 and suspension HL-60 cell lines revealed no apparent toxic effects of hPEMC of different architecture on live cells. Interaction of hPEMC with peritoneal macrophages for the course of 48 h resulted in partial deformation and degradation of microcapsules accompanied by release of the content of their hydrophilic (BSA–fluorescein isothiocyanate conjugate (BSA-FITC)) and hydrophobic (RBITC) layer. Our results demonstrate the functional efficiency of novel hybrid microcarriers and their potential for joint delivery of drugs with different physico-chemical properties in complex therapy.
Highlights
Most of the current systems of drug delivery enable loading and delivery of a single therapeutic agent [1–4]
EDTA, zimozan were all obtained from Sigma-Aldrich (Saint Louis, MO, USA); Phosphate buffered Saline (PBS), DMEM/F12, trypsin, penicillin and streptomycin were purchased from PanEco (Moscow, Russia); Fetal calf serum (FCS) was obtained from Invitrogen (Carlsbad, CA, USA); Chloroform was obtained from Chimmed (Moscow, Russia); DMSO was obtained from Panreac (Castellar del Vallès, Spain)
Ultrastructural analysis of the resulting microcapsules revealed the absence of regular structure in their external shell, which can be regarded as an advantage since such architecture accelerates hybrid polyelectrolyte microcapsules (hPEMC) degradation in vitro
Summary
Most of the current systems of drug delivery enable loading and delivery of a single therapeutic agent [1–4]. Simultaneous delivery of several compounds with different physical and chemical properties into the same target cells/tissue is known as combination drug delivery. Combination drug delivery systems offer a number of advantages, such as alleviation of multiple drug resistance, pharmacological synergy between the delivered compounds, as well as options to regulate bioavailability of the drugs in order to minimize their side effects. The existing systems for hydrophobic compound delivery, emulsion-based and spraying drying techniques in particular, do not meet the requirements for wider translational application. These methods are limited by low efficiency of hydrophobic compound loading, high manufacturing costs, and above all, the complexity of synthesis. The method of precipitation on the template appears advantageous, since it allows to alleviate these shortcomings [5–10]
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