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    Ultrasonically Assisted Preparation of Polysaccharide Microcontainers for Hydrophobic Drugs
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    Abstract:
    Stable polysaccharide microcontainers are fabricated by ultrasonically assisted procedure. Ultrasound induces formation of permanent microcontainer shell due to interaction between chitosan and xanthan gum. The obtained system has a core-shell structure with high loading capacity for hydrophobic molecules. The permanent polymer shell thickness of 7-10 nm allows to maintain the microcontainer stability for more than 4 months. The microcontainers in a wide size range of 350-7500 nm were obtained by changing an overall emulsion viscosity. Uptake of the microcontainers by mouse melanoma M3 cells was studied by flow cytometry and confocal microcscopy.
    An experimental protocol has been developed for synthesizing stable core–shell microcapsules using a biopolymer, chitosan, lacking cross-linkable thiol functional groups. In the first step, thiol moieties were introduced into the backbone of chitosan using DL-N-acetylhomocysteine thiolactone (AHT). In the second step, AHT-modified chitosan shelled microcapsules, encapsulating an oil core, were successfully prepared using high intensity 20 kHz ultrasound. The size of chitosan and AHT modified chitosan microcapsules was found to be in the range of 1–15 μm. The thickness of the microcapsule shell increased with an increase in thiol content. The mechanical properties of microcapsules were evaluated by subjecting the microcapsules to compressive forces by colloidal probe AFM. The stiffness and the Young's modulus of the shell of microcapsules were determined by analyzing the force versus indentation data using Reissner's theory for indentation of thin elastic shells. The stiffness of AHT modified chitosan microcapsules was found to be higher than unmodified chitosan microcapsules. The viability of microcapsules to be embedded into processed food, pharmaceutical and cosmetic products was tested via numerical simulations. The confined capsule in the micro-channel was subjected to linear shear and uniform flows. We used finite element numerical simulations to determine the deformation of microcapsules in flow as a function of shear rate and thickness of the shell. The deformation of capsule was found to be linear with an increase in the shear rate. The deformation decreased with an increase in the thickness of the shell. Based on the simulations, we predict that the microcapsules would survive processing conditions and shear rates used in industrial applications.
    Biopolymer
    Indentation
    Citations (13)
    Hollow poly(Lactic Acid) (PLA) microcapsules were fabricated using the bubble template method. In this method, microbubbles nucleated inside droplets of a dichloromethane solution of PLA which were located in a continuous phase of poly(vinyl alcohol). PLA-covered microbubbles formed when PLA adsorbed to the bubble surface by physisorption. Then, the coated microbubbles were spontaneously released from the droplet´s interior into the continuous phase. To increase the production yield of hollow microcapsules in this method, ultrasound was applied to enhance bubble nucleation inside the droplets. Thus to attain uniform hollow PLA microcapsules, the optimum PLA concentration with ultrasound was 30 g L-1, which is higher than that without ultrasound (2 g L-1). At the optimum concentration, the average radius was 0.54 μm, with a polydispersity index of 21.2%. It was found that the equilibrium size of the microbubble template radius was the same with and without ultrasound. The production yield had a tenfold increase when ultrasound was employed.
    Dispersity
    Particle (ecology)
    Abstract BACKGROUND In some disease therapy, it is necessary to release multiple drugs continuously and orderly. This paper describes a technique for preparing a microparticle that can load two kinds of substances and release them at two different rates. RESULTS A core–shell structural microparticle was designed using liposome as core and hyaluronan/poly( N ‐isopropylacrylamide) ( HA / PNIPAM ) gel as shell. The core liposome keeps its vesicle structure after undergoing the whole crosslinking process. The microparticles are injectable at room temperature and become sticky when heated. The fluorescent loaded in the shell released 80% in 1 h, while that in the core kept releasing for 35 h. CONCLUSION The stability and function of liposomes are improved after being coated with a gel shell. Two kinds of fluorophores were successfully loaded into microparticles and released at two different rates. The main factors controlling the tracer diffusion are the microparticle properties, e.g. crosslink density and shell thickness. These microparticles can be used as injectable or implantable drug carriers by minimally invasive techniques. © 2012 Society of Chemical Industry
    Microparticle
    Entrapment
    Citations (4)
    Poly( l ‐lactide‐ co ‐glycolide) (PLGA) microspheres with diverse internal structures and different release behaviors were prepared via a modified double‐emulsion method by introduction of heparin or carboxymethyl chitosan in the inner aqueous phase and calcium chloride in the outer aqueous phase, respectively. The main factors affecting the microsphere morphology were systematically studied, including compositions in the inner aqueous phase, the oily phase, and the outer aqueous phase. The transmission electron microscope images demonstrated that the microspheres are featured with single core, hollow, and multicore structures when their sizes were less than 200 nm, in the range of 200–700 nm, and greater than 700 nm, respectively. In comparison with hollow PLGA microspheres, the PLGA microspheres with heparin and carboxymethyl chitosan in the inner aqueous phase also showed multicore and single core structures, respectively, and exhibited higher loading efficiencies and slower release rates by using bovine serum albumin as a model for bioactive substances. It was concluded that this study provided a facile method to prepare microspheres with single core, multicore, or hollow feature, and the tunability of the different internal structures and related release profiles enables these systems cater to specific requirements for potential applications in controlled biomolecule delivery for tissue regeneration. POLYM. ENG. SCI., 55:896–906, 2015. © 2014 Society of Plastics Engineers
    PLGA
    Aqueous two-phase system
    Bovine serum albumin
    Citations (7)
    Ibuprofen microcrystals sized between 5 and 40 μm have been encapsulated with polyelectrolyte multilayers (PEM) for the purpose of controlled release. The encapsulation was accomplished by a novel coating technology based on layer-by-layer assembly of oppositely charged polyelectrolytes. The biocompatible polyelectrolytes including chitosan, dextran sulfate, carboxymethyl cellulose, and sodium alginate were used as coating materials to fabricate PEM capsules with varying shell thicknesses from 20 to 60 nm. UV spectroscopy was employed to monitor the drug release processes in both pH 1.4 and pH 7.4 solutions. It was found that the release of ibuprofen from these microcapsules is dependent on several parameters such as the crystal size, the PEM capsule thickness, and the solubility of the core material in the bulk solutions. Our results reveal that the polysaccharide capsules can substantially prolong the release time of the encapsulated drug crystals.
    Carboxymethyl cellulose
    Ibuprofen
    Layer by layer
    Citations (415)
    In this article, we present a facile and robust method for the surfactant-free preparation of polynorepinephrine stabilised microcapsules templated from an oil-in-water emulsion. The resulting microcapsule structures are dependent on the concentration of Cu2+ used to catalyse norepinephrine polymerisation. When the concentration of Cu2+ increases, the diameter of the microcapsules and the thickness of the shell increase correspondingly. The mechanical and chemical stability provided by the polynorepinephrine shell are explored using surface pressure measurements and atomic force microscopy, demonstrating that a rigid and robust polynorepinephrine shell is formed. In order to demonstrate potential application of the microcapsules in sustained release, Nile red stained squalane was encapsulated, and pH responsive release was monitored. It was seen that by controlling pH, the release profile could be controlled, with highest release efficacy achieved in alkaline conditions, offering a new pathway for development of encapsulation systems for the delivery of water insoluble actives.
    Squalane
    Citations (6)