34 research outputs found
Stability of Self-Assembled Polymeric Micelles in Serum
The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in both serum and individual serum protein solutions. By encapsulating Förster resonance energy transfer pairs and following their release by fluorescence, these micelles demonstrated excellent thermodynamic and kinetic stability in the presence of serum. Further analyses by fast protein liquid chromatography and dynamic light scattering confirmed these data. Moreover, these micelles are compatible with red blood cells, as shown by a hemolysis assay. The stability and compatibility demonstrated in blood suggest that these micelles may be stable in vivo, which is critical for intravenous drug delivery applications. This comprehensive approach to understanding micelle stability and compatibility is broadly applicable
Cross-Reactive Sensor Arrays for the Detection of Peptides in Aqueous Solution by Fluorescence Spectroscopy
A simple but powerful method for the sensing of peptides in aqueous solution has been developed. The transition-metal complexes [PdCl2(en)], [{RhCl2Cp*}2], and [{RuCl2(p-cymene)} 2] were combined with six different fluorescent dyes to build a cross-reactive sensor array. The fluorescence response of the individual sensor units was based on competitive complexation reactions between the peptide analytes and the fluorescent dyes. The collective response of the sensor array in a time-resolved fashion was used as an input for multivariate analyses. A sensor array comprised of only six metal-dye combinations was able to differentiate ten different dipeptides in buffered aqueous solution at a concentration of 50 uM. Furthermore, the cross-reactive sensor could be used to obtain information about the identity and the quantity of the pharmacologically interesting dipeptides carnosine and homocarnosine in a complex biological matrix, such as deproteinized human blood serum. The sensor array was also able to sense longer peptides, which was demonstrated by differentiating mixtures of the nonapeptide bradykinin and the decapeptide kallidin
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PMSE 246-Amphiphilic polymeric nanoassemblies for recognition of metalloproteins
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Fluorophore-cored dendrimers for patterns in metalloprotein sensing
In fluorophore-cored dendrimers with peripheral binding functionalities, the effect of generation upon protein binding-induced fluorescence quenching can be unpredictable; this is because the increase in fluorophore-binding functionality distance with generation is also accompanied by an increase in the number of binding moieties and the interplay between the two features is utilized to create patterns for metalloprotein sensing
Fluorophore-cored dendrimers for patterns in metalloprotein sensing
In fluorophore-cored dendrimers with peripheral binding functionalities, the effect of generation upon protein binding-induced fluorescence quenching can be unpredictable; this is because the increase in fluorophore-binding functionality distance with generation is also accompanied by an increase in the number of binding moieties and the interplay between the two features is utilized to create patterns for metalloprotein sensing
Recommended from our members
PMSE 246-Amphiphilic polymeric nanoassemblies for recognition of metalloproteins
Interconnected Roles of Scaffold Hydrophobicity, Drug Loading, and Encapsulation Stability in Polymeric Nanocarriers
Polymer-based nanoassemblies have
emerged as viable platforms for
the encapsulation and delivery of lipophilic molecules. Among the
criteria that such carriers must meet, if they are to be effective,
are the abilities to efficiently solubilize lipophilic guests within
an assembled scaffold and to stably encapsulate the molecular cargo
until desired release is achieved through the actions of appropriately
chosen stimuli. The former feature, dictated by the inherent loading
capacity of a nanocarrier, is well studied, and it has been established
that slight variations in assembly structure, such as introducing
hydrophobic content, can improve miscibility with the lipophilic guests
and increase the driving force for encapsulation. However, such clear
correlations between assembly properties and the latter feature, nanocarrier
encapsulation stability, are not yet established. For this purpose,
we have investigated the effects of varying hydrophobic content on
the loading parameters and encapsulation stabilities of self-cross-linked
polymer nanogels. Through investigating this nanogel series, we have
observed a fundamental relationship between nanoassembly structure,
loading capacity, and encapsulation stability. Furthermore, a combined
analysis of data from different loading amounts suggests a model of
loading-dependent encapsulation stability that underscores an important
correlation between the principal features of noncovalent encapsulation
in supramolecular hosts
Self-Cross-Linked Polymer Nanogels: A Versatile Nanoscopic Drug Delivery Platform
Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. By introducing variations into the precursor polymer, such as molecular weight and the relative percentages of hydrophilic OEG units and hydrophobic PDS functionalities, we have achieved significant control over nanogel size. We show that the noncovalently encapsulated guest molecules can be released in response to a redox trigger, glutathione (GSH). Stability of dye encapsulation inside the nanogels and tunability in the release of guest molecules have been demonstrated through in vitro fluorescence resonance energy transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast cancer cells (MCF-7) with nanogels of different cross-linking density to demonstrate that it plays a key role in the stable encapsulation of hydrophobic drug molecules and the cell-uptake efficiencies.close14913
Facile Preparation of Nanogels Using Activated Ester Containing Polymers
A facile methodology to prepare water-dispersible nanogels
based
on pentafluorophenyl acrylate and polyethylene glycol methacrylate
random copolymer and diamine cross-linkers has been developed. The
cross-linking reaction was characterized by FTIR and <sup>19</sup>F NMR. We show that those nanogels are (<i>i</i>) water-dispersible;
(<i>ii</i>) can conveniently encapsulate lipophilic guest
molecules; (<i>iii</i>) can be prepared with different nanosizes;
and (<i>iv</i>) are engineered to allow for surface decoration
with additional functional groups