9 research outputs found
Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line
Polymer particles consisting of a biodegradable poly[lactide-co-glycolide] (PLGA) core and a thermoresponsive shell have been formulated to encapsulate the dye rhodamine 6G and the potent cytotoxic drug paclitaxel. Cellular uptake of these particles is significantly enhanced above the thermal transition temperature (TTT) of the polymer shells in the human breast carcinoma cell line MCF-7 as determined by flow cytometry and fluorescence microscopy. Paclitaxel-loaded particles display reduced and enhanced cytotoxicity below and above the TTT respectively compared to unencapsulated drug. The data suggests a potential route to enhanced anti-cancer efficacy through temperature-mediated cell targeting.© The Royal Society of Chemistry 2013
Optimizing formulation parameters for the development of carvedilol injectable <i>in situ</i> forming depots
In situ forming depots (ISFDs) represent attractive alternatives to the conventional sustained drug delivery systems. Carvedilol, a short half-life drug used on a daily basis to manage chronic conditions, could benefit from this technology. The aim of this work was to develop, for the first time, a new injectable long-acting carvedilol-ISFD. Accordingly, 4 different grades of polyesters with varying properties as i) lactide-to glycolide ratio (polylactide-co-glycolide (PLGA) vs. polylactide (PLA)), and ii) end functionality (acid- vs. ester-capped) were utilized for the preparation of ISFD formulations. In addition, 4 different organic solvents with varying properties (i.e. N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), ethyl acetate, and benzyl benzoate) were also investigated. It was found that NMP and DMSO were more suitable for the formation of depots. Furthermore, all ISFD formulations demonstrated excellent encapsulation efficiency (i.e. 96–98%). Interestingly, both PLGA-based ISFDs (acid-capped and ester-capped) exhibited similar release behaviors and were able to extend carvedilol release over 30 days. On the other hand, acid-capped and ester-capped PLA-based ISFDs exhibited slower release over the 30 days with an average release of only 36% and 60%, respectively. In conclusion, the developed carvedilol-ISFDs resulted in a tunable extended-release behavior, simply by choosing the appropriate grade of polymer. These results open the door toward a novel injectable carvedilol-ISFD formulation.</p
Synergistic antibacterial activity of silver nanoparticles and hydrogen peroxide.
The increasing challenge of antibiotic resistance requires not only the discovery of new antibiotics, but also the development of new alternative approaches. Herein, the synergistic antibacterial activity of silver nanoparticles and hydrogen peroxide combination is reported. Unlike the bacteriostatic or slightly bactericidal activity achieved by using each agent alone, using these two agents in combination, even at relatively low concentrations, resulted in complete eradication of both the Gram negative Escherichia coli and the Gram positive Staphylococcus aureus in short treatment times indicating a clear synergistic effect between them. Modifying the surface chemistry of silver nanoparticles and the accompanied change in their surface charge enabled a further enhancement of such synergistic effect implying the importance of this aspect. Mechanistically, a Fenton-like reaction between silver nanoparticles and hydrogen peroxide is discussed and hypothesized to be the basis of the observed synergy. Achieving such a significant antibacterial activity at low concentrations reduces the potential toxicity of these agents and hence enables their utilization as an alternative antibacterial approach in wider range of applications
Thermoresponsive polymer colloids for drug delivery and cancer therapy
Many difficulties in treating cancer arise from the problems in directing highly cytotoxic agents to the deseased tissues, cells and intracellular compartments. Many drug delivery systems have been devised to address this problem, including those that show a change in properties in response to a temperature stimulus. In particular, colloidal materials based on thermoresponsive polymers offer a means to transport drugs selectively into tumour tissues that are hyperthermic, either intrinsically or through the application of clinical procedures such as localised heating. In this paper, the key attributes of thermoresponsive polymer colloids are considered, a number of important recent examples are discussed and the possible future developments of these materials are evaluated. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Facile synthesis of responsive nanoparticles with reversible, tunable and rapid thermal transitions from biocompatible constituents
Responsive polymeric nanoparticles composed of hybrid block co-polymers were prepared from biocompatible components that displayed rapid, tunable and multiply reversible transitions in response to change of temperature
Colloidal Stability of Citrate and Mercaptoacetic Acid Capped Gold Nanoparticles upon Lyophilization: Effect of Capping Ligand Attachment and Type of Cryoprotectants
For
various applications of gold nanotechnology, long-term nanoparticle
stability in solution is a major challenge. Lyophilization (freeze–drying)
is a widely used process to convert labile protein and various colloidal
systems into powder for improved long-term stability. However, the
lyophilization process itself may induce various stresses resulting
in nanoparticle aggregation. Despite a plethora of studies evaluating
lyophilization of proteins, liposomes, and polymeric nanoparticles,
little is known about the stability of gold nanoparticles (GNPs) upon
lyophilization. Herein, the effects of lyophilization and freeze–thaw
cycles on the stability of two types of GNPs: Citrate-capped GNPs
(stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic
acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic
acid, MAA-GNPs) are investigated. Both types of GNPs have similar
core size and effective surface charge as evident from transmission
electron microscopy and zeta potential measurements, respectively.
Plasmon absorption of GNPs and its dependence on nanoparticle aggregation
was employed to follow stability of GNPs in combination with dynamic
light scattering analysis. Plasmon peak broadening index (PPBI) is
proposed herein for the first time to quantify GNPs aggregation using
nonlinear Gaussian fitting of GNPs UV–vis spectra. Our results
indicate that Cit-GNPs aggregate irreversibly upon freeze–thaw
cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable
stability under the same conditions. Cit-GNPs exhibit no significant
aggregation in the presence of cryoprotectants (molecules that are
typically used to protect labile ingredients during lyophilization)
upon freeze–thaw cycles and lyophilization. The effectiveness
of the cyroprotectants evaluated was on the order of trehalose or
sucrose > sorbitol > mannitol. The ability of cryoprotectants
to prevent
GNPs aggregation was dependent on their chemical structure and their
ability to interact with the GNPs as assessed with zeta potential
analysis
Colloidal Stability of Citrate and Mercaptoacetic Acid Capped Gold Nanoparticles upon Lyophilization: Effect of Capping Ligand Attachment and Type of Cryoprotectants
For
various applications of gold nanotechnology, long-term nanoparticle
stability in solution is a major challenge. Lyophilization (freeze–drying)
is a widely used process to convert labile protein and various colloidal
systems into powder for improved long-term stability. However, the
lyophilization process itself may induce various stresses resulting
in nanoparticle aggregation. Despite a plethora of studies evaluating
lyophilization of proteins, liposomes, and polymeric nanoparticles,
little is known about the stability of gold nanoparticles (GNPs) upon
lyophilization. Herein, the effects of lyophilization and freeze–thaw
cycles on the stability of two types of GNPs: Citrate-capped GNPs
(stabilized via weakly physisorbed citrate ions, Cit-GNPs) and mercaptoacetic
acid-capped GNPs (stabilized via strongly chemisorbed mercaptoacetic
acid, MAA-GNPs) are investigated. Both types of GNPs have similar
core size and effective surface charge as evident from transmission
electron microscopy and zeta potential measurements, respectively.
Plasmon absorption of GNPs and its dependence on nanoparticle aggregation
was employed to follow stability of GNPs in combination with dynamic
light scattering analysis. Plasmon peak broadening index (PPBI) is
proposed herein for the first time to quantify GNPs aggregation using
nonlinear Gaussian fitting of GNPs UV–vis spectra. Our results
indicate that Cit-GNPs aggregate irreversibly upon freeze–thaw
cycles and lyophilization. In contrast, MAA-GNPs exhibits remarkable
stability under the same conditions. Cit-GNPs exhibit no significant
aggregation in the presence of cryoprotectants (molecules that are
typically used to protect labile ingredients during lyophilization)
upon freeze–thaw cycles and lyophilization. The effectiveness
of the cyroprotectants evaluated was on the order of trehalose or
sucrose > sorbitol > mannitol. The ability of cryoprotectants
to prevent
GNPs aggregation was dependent on their chemical structure and their
ability to interact with the GNPs as assessed with zeta potential
analysis
Multicomponent Synthetic Polymers with Viral-Mimetic Chemistry for Nucleic Acid Delivery
The ability to deliver genetic material for therapy remains
an
unsolved challenge in medicine. Natural gene carriers, such as viruses,
have evolved sophisticated mechanisms and modular biopolymer architectures
to overcome these hurdles. Here we describe synthetic multicomponent
materials for gene delivery, designed with features that mimic virus
modular components and which transfect specific cell lines with high
efficacy. The hierarchical nature of the synthetic carriers allows
the incorporation of membrane-disrupting peptides, nucleic acid binding
components, a protective coat layer, and an outer targeting ligand
all in a single nanoparticle, but with functionality such that each
is utilized in a specific sequence during the gene delivery process.
The experimentally facile assembly suggests these materials could
form a generic class of carrier systems that could be customized for
many different therapeutic settings