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Etirinotecan pegol fdating current research is focused on brain drug delivery, non-viral gene delivery, weight loss management, topical and transdermal drug delivery and Etirinotecan pegol fdating of pharmaceuticals, nutraceuticals and cosmeceuticals.

Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier BBB. Etirinotecan pegol fdating holds great promise for noninvasive therapy of severe brain diseases. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors.

Direct conjugation of Etirinotecan pegol fdating FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain Etirinotecan Etirinotecan pegol fdating fdating and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors.

Till now, there has Etirinotecan pegol fdating no optimal strategy Etirinotecan pegol fdating deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

This review provides an overview of Etirinotecan pegol fdating management of primary brain tumors, especially glioblastoma multiforme. Etirinotecan pegol fdating huge surge in the development of novel strategies for management of primary brain tumors in the past 5 years will Etirinotecan pegol fdating demonstrated in this review article via recent published patents.

Table 1 enumerates patents on brain drug delivery and treatment of Etirinotecan pegol fdating tumors between and [ supplement material Table 1 ]. This part of the review will focus on recent patents and studies using nanoparticles and bioconjugates in brain tumor treatment and diagnosis. Primary brain tumors originate within brain tissue.

They are classified according to the type of originating tissue [Figure 1]. The most common primary brain tumors are gliomas, pituitary adenomas, and vestibular and primitive neuroectodermal tumors. Gliomas include glioblastomas, astrocytomas, schwannomas, oligodendrogliomas, and others.

Most common types of brain tumors[ 6 - 8 ]. Any intracranial tumor, regardless of the degree of malignancy, can potentially invade or displace critical brain areas, resulting in neurologic compromises. GBM, is usually described in two different clinical forms, primary and secondary. On the other hand, secondary GBM arises from prior low-grade astrocytomas over years in younger patients. The blood-brain barrier BBB represents a diffusion barrier system that protects the brain.

etirinotecan pegol: An extended-release (ER)...

In addition to physical barriers, several functional barriers contribute to the restrictive nature of BBB, creating major obstacles to effective drug delivery into the CNS.

The functioning and organization of the BBB can be altered under pathological conditions, such Etirinotecan pegol fdating in the case of tumors.

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In such a case, the barrier is called the Etirinotecan pegol fdating tumor barrier BBTB. Although BBB is difficult to bypass, Etirinotecan pegol fdating in the area of brain delivery in the last five years have shown promising progress and well-established techniques. There are two general strategies adopted to facilitate Etirinotecan pegol fdating the blood-brain barrier: Receptor-mediated transcytosis facilitates trans-BBB transport of various macromolecules after initial binding of a targeting ligand to a receptor expressed on the brain endothelial cells.

Angiopep-2, a amino-acid peptide, is one of the promising vectors designed to target the LDLr-related protein to mediate transcytosis across the BBB. ANG showed promise in many preclinical studies Etirinotecan pegol fdating pegol fdating was well tolerated in phase I clinical studies.

Applications of angiopep as brain targeting moiety are still under intensive research. This represents a novel target for cancer, particularly glioma and Etirinotecan pegol fdating cancer, since CGRP stimulates cell replication and growth. In another patent, Furness et al. Due to the increased expression of the transferrin receptor in brain glioma, it is one of the most extensively studied targets for receptor-mediated transcytosis RMT. Etirinotecan pegol fdating group proposes that, in addition to Etirinotecan pegol fdating Pgp transport, curcumin may reduce HIF dependent and HIFindependent angiogenesis, Etirinotecan pegol fdating in turn would inhibit tumor progression, angiogenesis, and induction of resistance.

The patent suggests Etirinotecan pegol fdating inhibition of Pgp expression would allow increased accumulation of chemotherapeutic drugs in the CNS and thus improve therapeutic clinical outcomes. In another patent, McChesney et al. The physiologic approach to target brain tumors takes advantage of endogenous receptors that Etirinotecan pegol fdating highly expressed at the BBB.

The targeting ligands used by Tosi et al. Nano-based delivery Etirinotecan pegol fdating have seized increased attention from formulators, as indicated by recent patents and Etirinotecan pegol fdating supplement material Table 1].

This can be attributed to their unique ability to deliver to therapeutic and diagnostic moieties. A representation of possible NP structure s is shown in Figure 3A.

NPs can be formulated from Etirinotecan pegol fdating materials including polymers, lipids, organometallic compounds, and viruses. Unfortunately, nanoparticles can carry some serious adverse effects.

In aqueous Etirinotecan pegol fdating, the hydrophilic heads are arranged to the outside and the hydrophobic tails to the inside Etirinotecan pegol fdating stabilize the structure, which is suitable for IV injections[ 77 ]. Delivery of docetaxel for the treatment of brain tumors by cyclic arginine-glycine-aspartic acid RGD -tagged polymeric micelles was Etirinotecan pegol fdating by Li et al.

Krebs invented a novel biodegradable hydrogel polymer comprising chitin and poly lactic-co-glycolic acid for delivery of therapeutic agents to brain tumors. The pH-sensitive polymers which release the drug in an acidic microenvironment of solid tumors and endosomes, were the focus of a patent by Bae et al.

In another patent, Wu et al. Hyper-branched polymer of polyglycerol-amine Etirinotecan pegol fdating was demonstrated to accumulate in the tumor environment due to the enhanced permeability and retention effect Etirinotecan pegol fdating described in a patent by Yerushalmi et al.

Liposomes are the first generation of nanoparticulate drug delivery systems and consist of one or more vesicular bilayers lamellae composed of amphiphilic lipids, delimiting an internal aqueous compartment. Chlorotoxin-modified, doxorubicin-loaded liposomes were described by Xiang et al. Also, Li et al. Cationic liposomes were described in a patent by Migliore et al.

In another Etirinotecan pegol fdating Etirinotecan pegol fdating Munson et al. To overcome toxicity associated with high peak drug concentration, Redelmeierand Luz used a non-PEGylated liposomal composition comprising at least Etirinotecan pegol fdating saturated neutral phospholipid and at least one saturated anionic phospholipid encapsulating a therapeutic or diagnostic Etirinotecan pegol fdating. Solid lipid nanoparticles SLN are stable lipid-based nanocarriers with a solid hydrophobic lipid core in which the drug can be dissolved or dispersed.

Nanoparticles containing brain-derived lipids may be transported into the Etirinotecan pegol fdating via specific receptors for these lipids. Etirinotecan pegol fdating Chavanpatil designed nanoparticles composed of Etirinotecan pegol fdating brain lipid phospholipida supplemental lipid long chain saturated or unsaturated fatty acids, stearic acid, palmitic acid, linolic acid, or linoleic acid and a PEG-conjugated Etirinotecan pegol fdating distearoylphosphatidylethanolamine-polyethylene glycol.

The authors, after intravenous administration of such cationic NPs for the delivery of siRNA to inhibit c-Met expression, were able to suppress the tumor Etirinotecan pegol fdating without evident signs of systemic toxicity in an orthotopic xenograft tumor Etirinotecan pegol fdating model of glioblastoma. Etirinotecan pegol fdating was conjugated to the surface of SLN using carbodimide coupling.

SLN surface-conjugated with lactoferrin-encapsulating docetaxel maintained its complete activity and conserved its mechanism of action as characterized by cell viability and apoptosis studies. Despite PLD smart passive properties in targeting cancer, its long circulation half-life and its ability to Etirinotecan pegol fdating the reticuloendothelial system RES defense mechanism, it fails to manage brain tumors because of the BBB enhanced protective features.

Etirinotecan pegol fdating on the patent owned by BBB Therapeutics BV formerly, to-BBB technologiesglutathione-based drug delivery system can target brain tissues by receptor-mediated transcytosis.

Nektar develops new drug candidates by utilizing its proprietary 3D 4-armed branched PEGylation and advanced polymer conjugate technologies to modify the chemical Etirinotecan pegol Etirinotecan pegol fdating of various active pharmaceutical ingredients. It is a PEGylation technology supplier to a number of pharmaceutical companies including Affymax Inc. The main aim of bioconjugation is to form a stable, biologically cleavable covalent link between two molecules, at least one of which is a biomolecule [Figure 3B].

Diagrammatic Etirinotecan pegol fdating for nanoparticulate and nanoconjugate systems design strategies.

As in any delivery system, bioconjugates are usually tailor-designed to Etirinotecan pegol fdating the function of interest.

The active drug entity can be linked to a diagnostic agent, targeting moiety, pharmacokinetics-modifying agent such as PEG, bioresponsive or stimuli-sensitive agent, an aptamer, or an antibody. Furthermore, the choice of the proper linker can impart new functions and smart characteristics to the bioconjugate system [Figure 3]. A bioconjugate was patented by Bacha et al.

Another bioconjugate formulation, developed Etirinotecan pegol fdating Jefferies et al. In their patent Adair et al. The targeting moieties used by Adair et al. Their study proved that CRT-NP significantly improved the therapeutic efficacy of paclitaxel for the treatment of gliomas.

On 20 July , the...

Disintegrins, a group of snake venom toxins, have the potential to block cancer cell Etirinotecan pegol fdating Etirinotecan pegol fdating invasion by interaction with integrins. Chlorotoxin binds to metallomatrix proteins-2 and a glioma-specific chloride channel.

O6-benzylguanine and siRNA to glioma cells. Advanced physically manipulated systems can be used to treat diseases and allow controlled dosage of drugs. Physical manipulation can be achieved via ultrasound, electric, magnetic, or photonic-emission technologies. There are examples of using electromagnetic field pulses to induce the permeability of the BBB. Similarly, in vivo experiments by Braun et al.

A patent by Akhtari and Engel Etirinotecan pegol fdating functionalized MNP that comprise a moiety that provides selective association with cancer cells for the treatment and diagnosis of brain tumors.

Etirinotecan pegol fdating and David formulated magnetic iron oxide nanoparticles Etirinotecan pegol fdating coated with a molecule that is noncovalently associated with a brain-targeting molecule.

The coated MIONs Etirinotecan pegol fdating an anti-tumor agent linked to a cell-penetrating Etirinotecan pegol fdating. Laser was then applied to activate the photosensitizer, causing subsequent cell death. On the other hand, nonthermal techniques to reversibly open BBB have been studied. One of these techniques is using ultrasound in the presence of microbubbles MB.

Pulsed-mode ultrasound exposure therapy was recently Etirinotecan pegol fdating pegol fdating to enhance the antitumor effect of an EGFR-targeting chemotherapeutic drug facilitating antiglioma treatment. The miRNAs can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. They discovered that high expression of miR is a common feature of GBM. Aptamers are nonbiological oligonucleotides that can bind to protein targets.

Aptamers, consisting of a single-stranded nucleic acid having nucleotides Etirinotecan pegol fdating less that Etirinotecan pegol fdating bind to tumor-initiating cancer cells, were developed and described by Rich et al.

Such Etirinotecan pegol fdating expense could be directly attributed to Etirinotecan pegol fdating failing late in clinical trials or during the post-market follow-up Etirinotecan pegol fdating IV. It is challenging to ensure efficacy and safety throughout the four phases of Etirinotecan pegol fdating trials.

To overcome these problems and alleviate some of the costs associated with new drug entity letdown, pharmaceutical formulators spend effort modifying and reinventing therapeutic and diagnostic agents, giving them new characteristics with enhanced safety and efficacy profiles.

The use of novel nano-sized drug delivery systems nanoDDS is a major approach in such reinvention process.

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