Search results for "Delivery"

Aggregation behavior of amphiphilic p(HPMA)-co-p(LMA) copolymers studied by FCS and EPR spectroscopy.

2012

A combined study of fluorescence correlation spectroscopy and electron paramagnetic resonance spectroscopy gave a unique picture of p(HPMA)-co-p(LMA) copolymers in aqueous solutions, ranging from the size of micelles and aggregates to the composition of the interior of these self-assembled systems. P(HPMA)-co-p(LMA) copolymers have shown high potential as brain drug delivery systems, and a detailed study of their physicochemical properties can help to elucidate their mechanism of action. Applying two complementary techniques, we found that the self-assembly behavior as well as the strength of hydrophobic attraction of the amphiphilic copolymers can be tuned by the hydrophobic LMA content or…

Poly(Ethylene Glycol) Dimethacrylates with Cleavable Ketal Sites: Precursors for Cleavable PEG-Hydrogels.

2017

The authors introduce poly(ethylene glycol) (PEG) based macromonomers containing acid-labile ketal moieties as well as terminal methacrylate units that are amenable to radical polymerization. The synthesis of PEGs of different molecular weights (ranging from 2000 to 13 000 g mol-1 with polydispersities <1.15) with a central ketal unit (PEG-ketal-diol) and their conversion to PEG-ketal-dimethacrylates (PEG-ketal-DMA) is introduced. Degradation rates of both PEG-ketal-diols and PEG-ketal-DMA are investigated by in situ 1 H NMR kinetic studies in deuterated phosphate buffer. Hydrogels containing 0, 5, or 10 wt% of PEG-ketal-DMA and 100, 95, or 90 wt% of PEG-DMA, respectively, are synthesized a…

Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

2021

Financial support by the Emil Aaltonen Foundation, the Sigrid Jusélius Foundation, the Magnus Ehrnrooth Foundation, Academy of Finland (grants no. 317042 and 331151), the Jane and Aatos Erkko Foundation and the Vilho, Yrjö and Kalle Väisälä Foundation of the Finnish Academy of Science and Letters is gratefully acknowledged Nanostructures based on DNA self-assembly present an innovative way to address the increasing need for target-specific delivery of therapeutic molecules. Currently, most of the chemotherapeutics being used in clinical practice have undesired and exceedingly high off-target toxicity. This is a challenge in particular for small molecules, and hence, developing robust and ef…

Minimalism in radiation synthesis of biomedical functional nanogels.

2012

A scalable, single-step, synthetic approach for the manufacture of biocompatible, functionalized micro- and nanogels is presented. In particular, poly(N-vinyl pyrrolidone)-grafted-(aminopropyl)methacrylamide microgels and nanogels were generated through e-beam irradiation of PVP aqueous solutions in the presence of a primary amino-group-carrying monomer. Particles with different hydrodynamic diameters and surface charge densities were obtained at the variance of the irradiation conditions. Chemical structure was investigated by different spectroscopic techniques. Fluorescent variants were generated through fluorescein isothiocyanate attachment to the primary amino groups grafted to PVP, to …

pH-Responsive protein nanoparticlesviaconjugation of degradable PEG to the surface of cytochromec

2020

Proteins represent a versatile biopolymer material for the preparation of nanoparticles. For drug delivery applications an acid-triggered disassembly and payload release is preferred. Herein, we present a protein nanoparticle system based on cytochrome c, which is surface-modified with acid-degradable polyethylene glycol (PEGylation). pH-Sensitivity was obtained through vinyl ether moieties distributed in the polyether backbone. When PEGylated, cytochrome c shows a different solubility behaviour in organic solvents, which allows for particle preparation using an emulsion-based solvent evaporation method. The resulting particles are stable under physiological conditions but degrade at acidic…

Co-transfection of star-shaped PDMAEMAs enhance transfection efficiency of protamine/pDNA complexes in the presence of serum

2018

Abstract In previous studies, we have found that un-complexed free cationic polymers greatly promote gene transfection efficiency of pDNA complexes. Dividing the gene transfection system into two parts, bound chains and free chains, we exploited mixing different biomaterials as the second component of our designed system to improve gene transfection outcome. In this study, we investigated the effectiveness of star-shaped poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) with different arm numbers as free chains (i.e., co-transfection agent) while using natural salmon protamine as bound chains. We explored the gene transfer ability of the system in both serum free and complete cell culture…

Preparation and Characterization of Aminoglycoside-Loaded Chitosan/Tripolyphosphate/Alginate Microspheres against E. coli

2021

Although aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria, the evolution of bacterial resistance mechanisms and their inherent toxicity have diminished their applicability. Biocompatible carrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, novel chitosan gel beads were synthesized by a double ionic co-crosslinking mechanism. Tripolyphosphate and alginate, a polysaccharide obtained from marine brown algae, were employed as ionic cross-linkers to prepare the chitos…

2019

In photodynamic therapy (PDT), photosensitizers and light are used to cause photochemically induced cell death. The selectivity and the effectiveness of the phototoxicity in cancer can be increased by a specific uptake of the photosensitizer into tumor cells. A promising target for this goal is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe a polysaccharide-based nanoparticle system suitable for targeted uptake and its photochemical and photobiological characterization. The photosensitizer 5, 10, 15, 20-tetraphenyl-21H, 23H-porphyrine (TPP) was encapsulated in spermine- and acetal-modified dext…

Reactive Self-Assembly and Specific Cellular Delivery of NCO-sP(EO-stat-PO)-Derived Nanogels

2018

This study presents the reactive self-assembly of isocyanate functional and amphiphilic six-arm, star-shaped polyether prepolymers in water into nanogels. Intrinsic molecular amphiphilicity, mainly driven by the isophorone moiety at the distal endings of the star-shaped molecules, allows for the preparation of spherical particles with an adjustable size of 100-200 nm by self-assembly and subsequent covalent cross-linking without the need for organic solvents or surfactants. Covalent attachment of a fluorescence dye and either the cell-penetrating TAT peptide or a random control peptide sequence shows that only TAT-labeled nanogels are internalized by HeLa cells. The nanogels thus specifical…

Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers

2020

Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with dif…