Search results for "Pegylation"
showing 10 items of 32 documents
PEGYLATED POLYASPARTAMIDE–POLYLACTIDE BASED NANOPARTICLES PENETRATING CYSTIC FIBROSIS ARTIFICIAL MUCUS
2016
Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide− polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene gly…
"A versatile post-polymerization modification method for polyglutamic acid: synthesis of orthogonal reactive polyglutamates and their use in ""click …
2013
In this article we describe a versatile methodology for the synthesis of polyglutamic acid (PGA) derivatives bearing orthogonal reactive sites. The reactive groups enable selective conjugation chemistry by copper catalyzed azide-alkyne coupling (CuAAC). PGA was derived in aqueous media as well as in organic media using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholinium chloride (DMTTM) salts. The spectra of attached chemical moieties ranges from simple PEGylation with 2,5,8,11,14,17,20-heptaoxadocosan-22-amine (mEG(6)NH2) to the incorporation of propargylamine, 11-azido-3,6,9-trioxaundecan-1-amine (NH2-EG(2)N-3), and 20-azido-3,6,9,12,15,18-hexaoxaicosan-1-amine (NH2-EG(6)N-3). Here…
Universal Concept for the Implementation of a Single Cleavable Unit at Tunable Position in Functional Poly(ethylene glycol)s
2013
Poly(ethylene glycol) (PEG) with acid-sensitive moieties gained attention particularly for various biomedical applications, such as the covalent attachment of PEG (PEGylation) to protein therapeutics, the synthesis of stealth liposomes, and polymeric carriers for low-molecular-weight drugs. Cleavable PEGs are favored over their inert analogues because of superior pharmacodynamic and/or pharmacokinetic properties of their formulations. However, synthetic routes to acetal-containing PEGs published up to date either require enormous efforts or result in ill-defined materials with a lack of control over the molecular weight. Herein, we describe a novel methodology to implement a single acetalde…
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…
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…
Hydrophilicity Regulates the Stealth Properties of Polyphosphoester‐Coated Nanocarriers
2018
Increasing the plasma half-life is an important goal in the development of drug carriers, and can be effectively achieved through the attachment of polymers, in particular poly(ethylene glycol) (PEG). While the increased plasma half-life has been suggested to be a result of decreased overall protein adsorption on the hydrophilic surface in combination with the adsorption of specific proteins, the molecular reasons for the success of PEG and other hydrophilic polymers are still widely unknown. We prepared polyphosphoester-coated nanocarriers with defined hydrophilicity to control the stealth properties of the polymer shell. We found that the log P value of the copolymer controls the composit…
Poly(sarcosine) surface modification imparts stealth-like properties to liposomes
2019
Circulation lifetime is a crucial parameter for a successful therapy with nanoparticles. Reduction and alteration of opsonization profiles by surface modification of nanoparticles is the main strategy to achieve this objective. In clinical settings, PEGylation is the most relevant strategy to enhance blood circulation, yet it has drawbacks, including hypersensitivity reactions in some patients treated with PEGylated nanoparticles, which fuel the search for alternative strategies. In this work, lipopolysarcosine derivatives (BA-pSar, bisalkyl polysarcosine) with precise chain lengths and low polydispersity indices are synthesized, characterized, and incorporated into the bilayer of preformed…
In vitro and in vivo efficacy of PEGylated diisopropyl fluorophosphatase (DFPase)
2011
Highly toxic organophosphorus compounds that irreversibly inhibit the enzyme acetycholinesterase (AChE), including nerve agents like tabun, sarin, or soman, still pose a credible threat to civilian populations and military personnel. New therapeutics that can be used as a pretreatment or after poisoning with these compounds, complementing existing treatment schemes such as the use of atropine and AChE reactivating oximes, are currently the subject of intense research. A prominent role among potential candidates is taken by enzymes that can detoxify nerve agents by hydrolysis. Diisopropyl fluorophosphatase (DFPase) from the squid Loligo vulgaris is known to effectively hydrolyze DFP and the …
Evaluation of nanoparticle aggregation in human blood serum.
2010
In a certain stage of development, the performance of nanoparticle- or polymer-drug conjugates is tested "in vivo", that is, in mice or rats. Besides pharmaceutical and chemical characterization, the structural characterization of such drug carrier systems in terms of size, size distribution, and shape is typically performed in physiological salt solution prior to animal tests. The present work introduces a simple method based on dynamic light scattering to monitor the particle size in blood serum. Utilizing a model system of pegylated poly-l-lysines (PLL-g-PEOx) of various degrees of pegylation, x, it is demonstrated that large aggregates may form in human serum solution that are not obser…
From Biocompatible to Biodegradable: Poly(Ethylene Glycol)s with Predetermined Breaking Points
2013
Poly(ethylene glycol) (PEG) is the gold standard polymer for biomedical applications. PEG is known for its biocompatibility and antifouling properties and is widely used for bioconjugation. However, like other synthetic polymers in the field, PEG is not biodegradable, limiting its use for parenteral formulations and protein conjugation to a molecular weight range with a specific upper limit (commonly 40–60 kDa) to avoid polyether accumulation in human tissue. For these biomedical applications, but also for other purposes such as cleavable hydrogels and templates for porous membranes, several routes for the insertion of in-chain biocleavable moieties, such as acetals or disulfides, into PEG …