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

Glutathione-triggered disassembly of isothermally responsive polymer nanoparticles obtained by nanoprecipitation of hydrophilic polymers

The encapsulation and selective delivery of therapeutic compounds within polymeric nanoparticles offers hope for the treatment of a variety of diseases. Traditional approaches to trigger selective cargo release typically rely on polymer degradation which is not always sensitive to the biological location of a material. In this report, we prepare nanoparticles from thermoresponsive polymers with a ‘solubility release catch’ at the chain-end. This release catch is exclusively activated in the presence of intracellular glutathione, triggering an ‘isothermal’ response and promoting a change in polymer solubility. This solubility switch leads to specific and rapid nanoparticle disassembly, release of encapsulated cargo and produces completely soluble polymeric side-products

Control of aggregation temperatures in mixed and blended cytocompatible thermoresponsive block co-polymer nanoparticles

A small library of thermoresponsive amphiphilic copolymers based on polylactide-block-poly((2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligoethylene glycol methacrylate)) (PLA-b-P(DEGMA)-co-(OEGMA)), was synthesised by copper-mediated controlled radical polymerisation (CRP) with increasing ratios of OEGMA:DEGMA. These polymers were combined in two ways to form nanoparticles with controllable thermal transition temperatures as measured by particle aggregation. The first technique involved the blending of two (PLA-b-P(DEGMA)-co-(OEGMA)) polymers together prior to assembling NPs. The second method involved mixing pre-formed nanoparticles of single (PLA-b-P(DEGMA)-co-(OEGMA)) polymers. The observed critical aggregation temperature Tt did not change in a linear relationship with the ratios of each copolymer either in the nanoparticles blended from different copolymers or in the mitures of pre-formed nanoparticles. However, where co-polymer mixtures were based on (OEG)9MA ratios within 5-10 mole% , a linear relationship between (OEG)9MA composition in the blends and Tt was obtained. The data suggest that OEGMA-based copolymers are tunable over a wide temperature range given suitable co-monomer content in the linear polymers or nanoparticles. Moreover, the thermal transitions of the nanoparticles were reversible and repeatable, with the cloud point curves being essentially invariant across at least three heating and cooling cycles, and a selected nanoparticle formulation was found to be readily endocytosed in representative cancer cells and fibroblasts

Novel thermo-responsive polymeric nanoparticles for cancer therapy

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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

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