11 research outputs found
Photolysis Triggered Sealing of Multilayer Capsules to Entrap Small Molecules
Novel
microcapsule systems containing UV-responsive diazonium groups were
fabricated as microcontainers for cargo substance encapsulation by
using a layer-by-layer (LbL) assembly technique. Upon direct exposure
to UV light with a wavelength of approximately 380 nm, the diazonium
groups of diazoresion (DAR) rapidly reacted with sulfonate or diazo-sulfonate
groups of counterpart polyelectrolytes, which converted electrostatic
interactions to covalent bonds, demonstrating an effective in situ
cross-linking within multilayers via photolysis. Such chemical transition
eliminated the paired ionic groups, therefore generating more hydrophobic
multilayer shells, offering a unique approach to seal the porous polyelectrolyte
capsule shells. Fluorescent molecule rhodamine B (RhB) was consequently
studied as a typical example for small molecule encapsulation. Results
indicated that the dye was remarkably retained within the microcapsules
after UV-triggered capsule shell sealing
UV-Cross-Linkable Multilayer Microcapsules Made of Weak Polyelectrolytes
Microcapsules composed of weak polyelectrolytes modified
with UV-responsive
benzophenone (BP) groups were fabricated by the layer-by-layer (LbL)
technique. Being exposed to UV lights, capsules shrunk in the time
course of minutes at irradiation intensity of 5 mW/cm<sup>2</sup>.
The shrinkage adjusted the capsule permeability, providing a novel
way to encapsulate fluorescence-labeled dextran molecules without
heating. Cross-linking within the capsule shells based on hydrogen
abstraction via excited benzophenone units by UV showed a reliable
and swift approach to tighten and stabilize the capsule shell without
losing the pH-responsive properties of the weak polyelectrolyte multilayers
Local and Sustained Activity of Doxycycline Delivered with Layer-by-Layer Microcapsules
Achieving localized delivery of small
molecule drugs has the potential
to increase efficacy and reduce off target and side effects associated
with systemic distribution. Herein, we explore the potential use of
layer-by-layer (LbL) assembled microcapsules for the delivery of doxycycline.
Absorbance of doxycycline onto core dextran sulfate of preassembled
microcapsules provides an efficient method to load both synthetic
and biodegradable microcapsules with the drug. Application of an outer
layer lipid coat enhances the sustained in vitro release of doxycycline
from both microcapsule types. To monitor doxycycline delivery in a
biological system, C2C12 mouse myoblasts are engineered to express
EGFP under the control of the optimized components of the tetracycline
regulated gene expression system. Microcapsules are not toxic to these
cells, and upon delivery to the cells, EGFP is more efficiently induced
in those cells that contain engulfed microcapsules and monitored EGFP
expression clearly demonstrates that synthetic microcapsules with
a DPPC coat are the most efficient for sustain intracellular delivery.
Doxycycline released from microcapsules also displayed sustained activity
in an antimicrobial growth inhibition assay compared with doxycycline
solution. This study reveals the potential for LbL microcapsules in
small molecule drug delivery and their feasible use for achieving
prolonged doxycycline activity
Adhesion of Polyelectrolyte Multilayers: Sealing and Transfer of Microchamber Arrays
Polyelectrolyte multilayer (PEM) films with array of
responsive
microchambers are promising candidates for site-specific release of
chemicals in small and precisely defined quantities on demand. It
requires effective sealing of the microchambers toward a support to
prevent leakage of a cargo. In this paper, we study the pressure-induced
adhesion of polyÂ(allylammonium)-polyÂ(4-styrenesulfonate) (PAH-PSS)
multilayers assembled on different templates toward the polyÂ(4-styrenesulfonate)-polyÂ(diallyldimethylammonium)
multilayer. The tensile bond strength increases from 0.4 to 3.5 MPa
upon the increase of PAH-PSS bilayers from 10 to 40, if assembled
on a silicon template. Weaker tensile bond strength of 0.35 MPa between
the PAH-PSS multilayer and a polyÂ(methylmethacrylate) (PMMA) template
results in adhesive break at this interface and allows mechanical
removal of the template. The successful PEM transfer is demonstrated
for templates of various geometrical patterns, while the tensile break
of a multilayer film happens for the others
Layer-by-Layer Assembled Multilayer Shells for Encapsulation and Release of Fragrance
Layer-by-layer
assembled shells are prospective candidates for encapsulation, stabilization,
storage, and release of fragrances. A shell comprising four alternative
layers of a protein and a polyphenol is employed to encapsulate the
dispersed phase of a fragrance-containing oil-in-water emulsion. The
model fragrance used in this work consists of 10 ingredients, covering
a range of typically employed aroma molecules, all premixed in equal
mass and with sunflower oil acting as the base. The encapsulated emulsion
is stable after 2 months of storage at 4 °C as revealed by static
light scattering and confocal laser scanning microscopy. Gas chromatography/mass
spectrometry data show that the encapsulation efficiency of 8 out
of 10 fragrance ingredients depends on the water solubility: the less
water-soluble an ingredient, the more of it is encapsulated. The amount
of these fragrance ingredients remaining encapsulated decreases linearly
upon emulsion incubation at 40 °C and the multilayer shell does
not hinder their release. The other two fragrance ingredients having
the lowest saturation vapor pressure demonstrate sustained release
over 5 days of incubation at 40 °C. The composition of released
fragrance remains almost constant over 3 days of incubation, upon
further incubation it becomes enriched with these two ingredients
when others start to be depleted
Functional Silver-Coated Colloidosomes as Targeted Carriers for Small Molecules
Colloidosomes have
attracted great interest in recent years because
of their capability for storage and delivery of small molecules for
medical and pharmaceutical applications. However, traditional polymer
shell colloidosomes leak low molecular weight drugs due to their intrinsic
shell permeability. Here, we report aqueous core colloidosomes with
a silver shell, which seals the core and makes the shell impermeable.
The silver-coated colloidosomes were prepared by reacting l-ascorbic acid in the microcapsule core with silver nitrate in the
wash solution. The silver shell colloidosomes were then modified by
using 4,4′-dithiodibutyric acid and cross-linked with rabbit
Immunoglobulin G (IgG). Label-free surface plasmon resonance was used
to test the specific targeting of the functional silver shell with
rabbit antigen. To break the shells, ultrasound treatment was used.
The results demonstrate that a new type of functional silver-coated
colloidosome with immunoassay targeting, nonpermeability, and ultrasound
sensitivity could be applied to many medical applications
Intracellular Delivery of Antioxidant CeO<sub>2</sub> Nanoparticles via Polyelectrolyte Microcapsules
Cerium
oxide nanoparticles (nanoceria) are regarded as one of the most promising
inorganic antioxidants for biomedical applications. Considering nanoceria
as a potential therapeutic agent, we aimed to develop a robust system
for its intracellular delivery using layer-by-layer polyelectrolyte
microcapsules. We have shown that citrate-stabilized cerium oxide
nanoparticles can be effectively incorporated into the structure of
polyelectrolyte microcapsules made from biodegradable and nonbiodegradable
polymers. The structure and morphology of synthesized microcapsules
were investigated and analyzed using confocal laser scanning microscopy,
scanning electron microscopy, transmission electron microscopy, energy-dispersive
X-ray spectroscopy, and UV/vis spectroscopy. Results of experiments
in vitro on B50 neuroblastoma cells confirmed nanoceria delivery into
the cell while maintaining their antioxidant properties. The results
presented confirm polyelectrolyte microcapsules to be an efficient
intracellular delivery system for therapeutic nanoparticles
Multilayer Capsules of Bovine Serum Albumin and Tannic Acid for Controlled Release by Enzymatic Degradation
With
the purpose to replace expensive and significantly cytotoxic positively
charged polypeptides in biodegradable capsules formed via Layer-by-Layer
(LbL) assembly, multilayers of bovine serum albumin (BSA) and tannic
acid (TA) are obtained and employed for encapsulation and release
of model drugs with different solubility in water: hydrophilic-tetramethylrhodamine-isothiocyanate-labeled
BSA (TRITC-BSA) and hydrophobic 3,4,9,10-tetra-(hectoxy-carbonyl)-perylene
(THCP). Hydrogen bonding is proposed to be predominant within thus
formed BSA/TA films. The TRITC-BSA-loaded capsules comprising 6 bilayers
of the protein and polyphenol are benchmarked against the shells composed
of dextran sulfate (DS) and poly-l-arginine (PARG) on degradability
by two proteolytic enzymes with different cleavage site specificity
(i.e., α-chymotrypsin and trypsin) and toxicity for murine RAW264.7
macrophage cells. Capsules of both types possess low cytotoxicity
taken at concentrations equal or below 50 capsules per cell, and evident
susceptibility to α-chymotrypsin resulted in release of TRITC-BSA.
While the BSA/TA-based capsules clearly display resistance to treatment
with trypsin, the assemblies of DS/PARG extensively degrade. Successful
encapsulation of THCP in the TRITC-BSA/TA/BSA multilayer is confirmed,
and the release of the model drug is observed in response to treatment
with α-chymotrypsin. The thickness, surface morphology, and
enzyme-catalyzed degradation process of the BSA/TA-based films are
investigated on a planar multilayer comprising 40 bilayers of the
protein and polyphenol deposited on a silicon wafer. The developed
BSA/TA-based capsules with a protease-specific degradation mechanism
are proposed to find applications in personal care, pharmacology,
and the development of drug delivery systems including those intravenous
injectable and having site-specific release capability
Image_1_Use of Submicron Vaterite Particles Serves as an Effective Delivery Vehicle to the Respiratory Portion of the Lung.jpg
<p>Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.</p
Image_2_Use of Submicron Vaterite Particles Serves as an Effective Delivery Vehicle to the Respiratory Portion of the Lung.jpg
<p>Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.</p