1,721,180 research outputs found
Self assembling nanocomposites for protein delivery: Supramolecular interactions of soluble polymers with protein drugs.
No full textTranslation of therapeutic proteins to pharmaceutical products is often encumbered by their inadequate physicochemical and biopharmaceutical properties, namely low stability and poor bioavailability. Over the last decades, several academic and industrial research programs have been focused on development of biocompatible polymers to produce appropriate formulations that provide for enhanced therapeutic performance. According to their physicochemical properties, polymers have been exploited to obtain a variety of formulations including biodegradable microparticles, 3-dimensional hydrogels, bioconjugates and soluble nanocomposites. Several soluble polymers bearing charges or hydrophobic moieties along the macromolecular backbone have been found to physically associate with proteins to form soluble nanocomplexes. Physical complexation is deemed a valuable alternative tool to the chemical bioconjugation. Soluble protein/polymer nanocomplexes formed by physical specific or unspecific interactions have been found in fact to possess peculiar physicochemical, and biopharmaceutical properties. Accordingly, soluble polymeric systems have been developed to increase the protein stability, enhance the bioavailability, promote the absorption across the biological barriers, and prolong the protein residence in the bloodstream. Furthermore, a few polymers have been found to favour the protein internalisation into cells or boost their immunogenic potential by acting as immunoadjuvant in vaccination protocols
Effective colloidal systems to switch proteins into drugs: state of art and perspectives.
No full textThe advances in biotechnology science together with the enhanced comprehension of protein structure-activity relationships have rapidly raised proteins to a dominant position in the pharmaceutical scenario1. Nevertheless, the therapeutic exploitation of these macromolecules is often hurdled by their inadequate physicochemical and biopharmaceutical properties.
Chemical, physical or enzymatic inactivation during formulation, storage and delivery, poor membrane permeability and rapid elimination from the body dramatically reduce the protein transformation into drugs. Furthermore, long term daily injections required chronic treatments has obvious drawbacks. Therefore, the use of protein drugs relies on the development of suitable formulations, which can satisfactorily overcome their intrinsic limitations and ameliorate the patient compliance.
Colloidal vectors such as bioconjugates, liposomes, nanoparticles and micelles have been successfully reshaped for protein delivery2.
With regard to chemical bioconjugation, PEGnology is actually considered a routinary technique for delivering poorly performing proteins3. Typically, PEGylation prolongs the permanence in the blood stream, enhances the stability and solubility and reduces the immunogenicity of proteins.
Throughout the last years, PEGnology has been rapidly evolving to provide new solutions to the demanding requisites for new therapeutics. Selective PEGylation strategies have been set up as alternatives to the random and extensive polymer conjugation used to obtain the first clinically approved therapeutics, PEG-asparaginase (Oncaspar) and PEG-adenosine deaminase (Adagen) 4.
Physical protein/polymer associations are deemed a valuable alternative tool to the chemical bioconjugation. Soluble polymers, namely polysaccharides and synthetic polymers, can be properly designed to yield protein/polymer supramolecular structures, either by specific or unspecific interactions that can provide for protein protection from enzyme degradation and immunorecognition and slow release of the native drug5.
In conclusion, soluble polymers can be successfully exploited to yield colloidal soluble systems for protein delivery. The choice of the polymer and accurate conjugation design, conjugation strategy are the key issues to obtain therapeutically efficient products. This involves a number of considerations including the physicochemical and therapeutic properties of the protein candidates.
Targetable cyclodextrins for anti-tumor drug delivery
No full textA synthesis procedure was set up aimed at preparing a new tumor targetable drug carrier based on -cyclodextrins by derivatization with different chemical moieties. The hydrophobic core was expanded by conjugation of alkyl chains and folic acid was attached through a PEG spacer aiming at confering tumor targeting capacity. The construct was extensively characterized by chromatography and spectroscopy tecniques. The curcumine inclusion capacity was evaluated by assessing the solubility and stability increase after inclusion in the new carrier
Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers
Full text linkOver the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the "stealth" properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed
Corona-like (guanidyl)-oligosaccharidic derivatives as cell-penetrating enhancers for intracellular delivery of colloidal therapeutic systems
No full textA novel class of cell-penetrating enhancers with unusual chemical structure is herein disclosed. Said cell-penetrating enhancers are non-linear and non peptidic (guanidyl)-oligosaccharidic derivatives, which can be easily obtained according to simple and reproducible synthetic steps. A wide array of cell penetration enhancers can be obtained by slight modification of the main structure oligosaccharidic backbone and in order to provide for their conjugation or physical combination with a variety of therapeutic systems. These molecules can be designed for conjugation to proteins or polymer therapeutics or for surface decoration of liposomes or nanoparticles. Finally, the cationic features and the penetration enhancer properties of the corona-like (guanidyl)-oligosaccharidic derivatives can be exploited for oligonucleotide, namely siRNA, or gene delivery
ASCORBATE-LINKED NANOSYSTEMS FOR BRAIN DELIVERY
No full textThe invention is based, at least in part, on the discovery of a method for targeting liposomes and micelles to brain cells. This discovery was exploited to develop the invention, which, in one aspect, features a method of delivering a lipid formulation to brain cell, comprising contacting the brain cell with lipid formulation, the lipid formulation comprising ascorbate or an ascorbate derivative on an outer surface of the lipid formulation, the ascorbate or the ascorbate derivative contacting a sodium-dependent vitamin C transporter (SVCT) on the brain cell to thereby deliver the lipid formulation to the brain cell. In certain embodiments, the lipid formulation is a liposome or micelle. In particular embodiments, the ascorbate linked to the liposome or micelle is not bound by a glucose transporter (GLUT), or has reduced binding capacity to GLUT relative to free ascorbate.
In some embodiments, the liposome or micelle comprises a phospholipid conjugated to the ascorbate or the ascorbate derivative at the C6 position of the ascorbate or the ascorbate derivative. In some embodiments the phospholipid comprises derivatized phospholipids. In particular embodiments the derivatized phospholipid comprises polyethylenglycol (PEG). In certain embodiments the ascrobate or ascorbate derivative is conjugated to the derivatized phospholipid via PEG. In some embodiments, the brain cell is an epithelial cell of the choroid plexus or an ependymal cell of the blood brain barrier. In some embodiments the brain cell trasports the liposome or micelle into the cerebrospinal fluid (CSF) of the brain. In other embodiments, after entering the CSF, the liposome or micelle contacts a second brain cell. In particular embodiments the second brain cell is a neuron, a glial cell, or an astrocyte or a brain turmor cell.
In some embodiments the liposome or the micelle further comprises a therapeutic agent or a detection agent.
In other aspect the invention features a method of delivering a therapeutic agent or a detection agent to a brain cell, comprising contacting the brain cell with a lipid formulation loaded with a therapeutic agent or detection agent, and ascorbate or an ascorbate derivative on the outer surface of the lipid formulation, the ascorbate or the ascorbate derivative contacting a sodium-dependent vitamin C transporter (SVCT) on the brain cell to thereby deliver the therapeutic agent or the detection agent to the brain cell
Synthesis and characterization of cathepsin K sensitive antitumour drug-polymer conjugate for bone targeting.
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