•Polyurethane microcapsules with different shapes are prepared.•The capsules can maintain their original shapes in aqueous solution.•The discal capsules are internalized with faster rate and higher amount by cells.The shape of particles is recognized as an important parameter to influence their interactions with cells. In this study, spherical and discal polyurethane microcapsules were prepared via an adsorption and crosslinking method on the templates with corresponding shapes in organic solvent. Both types of capsules could be well dispersed in aqueous medium and maintain their original shapes. The internalization behaviors of the microcapsules were investigated by co-incubation with RAW 264.7 and HepG2 cells. Compared with the spherical capsules, the discal microcapsules could be internalized with faster rate and higher amount by both types of cells. Both types of capsules did not show significant cytotoxicity even after co-incubation for 72 h at a high ratio of capsule to cell.Discal and spherical polyurethane microcapsules were prepared via a templating method to investigate the influence of shape on cellular internalization.Download high-res image (84KB)Download full-size image

Among several properties of colloidal particles, shape is emerging as an important parameter for tailoring the interactions between particles and cells. In this study, bowl-like multilayer microcapsules were prepared by osmotic-induced invagination of their spherical counterparts in a concentrated polyelectrolyte solution. The internalization behaviors of bowl-like and spherical microcapsules were compared by coincubation with smooth muscle cells (SMCs) and macrophages. The bowl-like capsules tended to attach onto the cell membranes from the bend side and could be enwrapped by the membranes of SMCs, leading to a faster uptake rate and larger accumulation inside cells than those of their spherical counterparts. These results are important for understanding the shape-dependent internalization behavior, providing useful guidance for further materials design especially in biomedical applications.Keywords: bowl-like; cellular uptake; microcapsules; osmotic pressure; polyelectrolyte; shape effect

Intelligent capsules are widely used as carriers for loading small molecules and particles for their capacity to respond to environmental stimuli. In this study, photo-responsive polyethyleneimine (PEI) microcapsules were fabricated using 4-bromomethyl-3-nitrobenzoic acid (BNBA) bearing a photodegradable ortho-nitrobenzyl group as a cross-linker. PEI-doped CaCO3 particles were used as the sacrificial templates, in which the PEI molecules were cross-linked by BNBA molecules under the activation of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) and N,N-diisopropylethylamine (DIEA). After the removal of CaCO3 particles by hydrochloric acid, the PEI–BNBA capsules were obtained. Since the C–N bond that formed via reaction of benzyl bromide and amine is photo-cleavable, the capsules could be decomposed under UV irradiation at 365 nm. The loaded macromolecules could be released upon UV irradiation, exhibiting the microcapsules’ potential applications in the field of controlled release.

Colloidal microcapsules (MCs) have received considerable attention in the fields of microencapsulation, drug delivery as well as microreactors due to their unique nanoparticles-composed structure. In this study, dual-responsive colloidal MCs based on host-guest interaction were successfully fabricated via a layer-by-layer assembly method on sacrificial solid templates. Ferrocene-modified polyethylenimine (PEI-Fc) and cyclodextrin-modified polystyrene nanoparticles (PS-CD NPs) were used as building blocks for assembly. The colloidal MCs could be disassembled into nano-components upon addition of competitive adamantane (Ad) molecules or in the solution with a pH lower than 4.

•The microspheres are fabricated via polyamine/salt assembly and stabilized via covalent crosslinking.•The surface of microspheres is modified with hyaluronic acid by layer-by-layer assembly method.•The pH sensitive dye and insensitive dye are labeled to endow the microspheres with ratiometric pH sensing property.•The microspheres can be selectively internalized by tumor cells and report the local pH environment.The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization.

Elastic polyurethane (PU) microcapsules were successfully fabricated via a simple and well controllable adsorption and crosslinking method on porous CaCO3 templates in organic solvent. The PU capsules possessed some amine groups, enabling well dispersion in water. These PU capsules with hydrophobic interiors could load hydrophobic substances such as drugs and dyes from organic solution spontaneously. And the loaded dyes can be well preserved. Their deformation and recovery behaviours were investigated after being forced to flow through a microchannel. Due to their good elasticity, more than 82% squeezed PU capsules could recover their original spherical shape even at a high deformation ratio of 32%. These elastic PU microcapsules with strong shape recovery ability may find diverse applications as microcontainer or microsensor which could survive through harsh conditions like forced deformation.

The widely used bovine serum albumin (BSA) nanoparticles (NPs) were modified with poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and aptamers to improve their suspension stability and targeting ability. For this to occur, a PAH-g-poly(ethylene glycol) (PAH-g-PEG–COOH) layer was further adsorbed onto the (PAH/PSS)2 multilayer-coated BSA NPs and used to covalently bond the aptamer AS1411, which is known to specifically bind the over-expressed nucleolin on cancer cell membranes. The PEGylated multilayer-coated BSA NPs showed good suspension stability in diverse media, in particular in a serum containing medium. By a mechanism of spontaneous deposition, doxorubicin (DOX) was effectively loaded into the pre-formed BSA NPs with both good encapsulation efficiency (98.6%) and loading percentage (9%). The loaded drug showed a pH-dependent release behaviour, i.e. faster at pH 5.5 than at pH 7.4. The multilayer coating did not significantly influence either both drug loading or release. In vitro cell culture demonstrated that the as-prepared BSA NPs could be specifically delivered to liver cancer cells, leading to higher cellular uptake and cytotoxicity.

Shrinking phenomenon of poly(allylamine hydrochloride) (PAH)/poly(styrene sulfonate, sodium salt) (PSS) multilayer microcapsules was observed when they were incubated in alkaline solutions containing Ca2+. The shrinking was universal to those polyelectrolyte multilayer capsules regardless of the wall thickness and wall compositions suppose the conditions were proper. The shrinking extent increased along with the increase of solution pH and Ca2+ concentration, and reached to a maximum value of 70% (from 7.4 to 2.3 μm). The shrunk capsules with a hollow structure and thick wall could well maintain their spherical shape in a dry state. During the capsule shrinking partial loss of the polyelectrolytes especially PSS took place, and the loss amount increased along with the increase of solution pH although the alteration patterns were different at lower Ca2+ concentration. The complexation of PSS with Ca2+, which is believed one of the major reasons governing the capsule shrinking, was demonstrated by X-ray photoelectron spectroscopy and turbidity experiment. The mechanism is proposed, which relies on the synergistic effects of deprotonation of PAH and screening of PSS by Ca2+ leading to the thermodynamically favored-capsule shrinking.

To improve the colloidal stability of bovine serum albumin (BSA) nanoparticles (NPs) in diverse mediums, poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and poly(allylamine hydrochloride)-graft-poly(ethylene glycol) (PAH-g-PEG) coating were coated on the surface of BSA NPs. Stabilities of the BSA NPs in diverse mediums with different surfaces were detected by dynamic light scattering (DLS). Multilayers and PAH-g-PEG coated BSA NPs can be well dispersed in various mediums with a narrow polydispersity index (PDI). The BSA NPs with the highest surface density of PEG show the best stability. The multilayers and PAH-g-PEG coating do not deter the pH-dependent loading and release property of BSA NPs. At pH 9, the encapsulation efficiency of doxorubicin reaches almost 99%, and the release rate at pH 5.5 is significantly higher than that at pH 7.4.

The deformation and recovery behaviors of multilayer microcapsules were investigated after being forced to flow through a microchannel. The microchannel device with a constriction (5.7 μm in depth) in the middle was designed, and the multilayer microcapsules with different size and layer thickness (and thereby different mechanical strength) were used. Deformation in the microchannel was observed for all the capsules with a size larger than the constriction height, and its extent was mainly governed by the difference between capsule size and constriction height. The squeezed microcapsules could recover their original spherical shape when the deformation extent was smaller than 16%, whereas permanent physical deformation took place when the deformation extent was larger than 34%. The capsules filled with polyelectrolytes could greatly enhance their shape recovery ability due to the higher osmotic pressure in the capsule interior and could well maintain the preloaded low-molecular-weight dyes regardless of the squeezing.

Ionic strength-responsive microcapsules with auto-fluorescence were fabricated by incubation of poly(allylamine hydrochloride) (PAH)-doped CaCO3 particles in triethylamine (Et3N), followed by core removal using HCl. Based on the combination of hydrophobic interaction and hydrogen bonding, PAH and Et3N formed a complex with a molar ratio of 3:1 (repeating unit of PAH: Et3N). The as-prepared capsules showed extraordinary stability against 1 M HCl, 1 M NaOH and 6 M urea solutions, and could swell or shrink reversibly in response to the ionic strength. Furthermore, the capsules possessed auto-fluorescence, allowing easily tracking of capsules during applications. Such interaction may be expanded to formation of stimuli-responsive multilayer films and other colloidal particles.

The widely used bovine serum albumin (BSA) nanoparticles (NPs) were modified with poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and aptamers to improve their suspension stability and targeting ability. For this to occur, a PAH-g-poly(ethylene glycol) (PAH-g-PEG–COOH) layer was further adsorbed onto the (PAH/PSS)2 multilayer-coated BSA NPs and used to covalently bond the aptamer AS1411, which is known to specifically bind the over-expressed nucleolin on cancer cell membranes. The PEGylated multilayer-coated BSA NPs showed good suspension stability in diverse media, in particular in a serum containing medium. By a mechanism of spontaneous deposition, doxorubicin (DOX) was effectively loaded into the pre-formed BSA NPs with both good encapsulation efficiency (98.6%) and loading percentage (9%). The loaded drug showed a pH-dependent release behaviour, i.e. faster at pH 5.5 than at pH 7.4. The multilayer coating did not significantly influence either both drug loading or release. In vitro cell culture demonstrated that the as-prepared BSA NPs could be specifically delivered to liver cancer cells, leading to higher cellular uptake and cytotoxicity.