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Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors.

BACKGROUND: Paclitaxel has been difficult to evaluate in preclinical tumor model systems because its poor solubility requires a Cremophor EL formulation, which results in lethal anaphylaxis. We tested the effectiveness of a novel polymeric micellar paclitaxel on androgen-independent tumor growth in the LNCaP tumor model. METHODS: Athymic male mice bearing LNCaP tumors were castrated and allowed to grow until their PSA levels increased to three times above precastration levels. The animals were then treated with 0.5 mg intravenous polymeric micellar paclitaxel once daily for the first 5 days o

[Determination of four antipyretic and analgesic drugs in water by solid-phase extraction coupled ultra-performance liquid chromatography-tandem mass spectrometry].

The widespread use of pharmaceutical and personal care products (PPCPs), including antipyretic and analgesic drugs, in the last two decades had led to the existence of PPCP residues in the environment, thus raising concerns about their pseudo-persistent nature and potential threat to human health. Generally, most of the detected contaminants are present at low levels (ranging from ng/L to μg/L) in environmental water. Therefore, advanced analytical methodologies are crucial to monitor the occurrence and distribution of antipyretic and analgesic drugs in environmental water. However, trace anal

Probing alpha-crystallin structure using chemical cross-linkers and mass spectrometry.

PURPOSE: Alternatives to X-ray crystallographic techniques are needed to probe the structure of the hetero-oligomeric lens protein alpha-crystallin. We utilized mass spectrometry for 3 dimensional analysis (MS3D) to study the quaternary structural characteristics of this important lens protein and molecular chaperone. METHODS: We have employed two types of chemical cross-linkers to probe key protein-protein and protein-solvent interactions of alpha-crystallin using MS3D. Native alpha-crystallin was exposed to 3,3'-dithiobis[sulfosuccinimidyl propionate] (DTSSP) and the common fixative, formal

Bioadhesive lipid compositions: self-assembly structures, functionality, and medical applications.

Lipid-based liquid crystalline compositions of phospholipids and diglycerides have unique bioadhesive properties with several medical applications, as exemplified by a lipid-based medical device indicated for management and relief of intraoral pain. The present paper describes the relation between self-assembly properties of phosphatidyl choline (PC) and glycerol dioleate (GDO) mixtures in the presence of aqueous fluids and functional attributes of the system, including: film formation and bioadhesion, intraoral coverage, acceptance by patients, and potential as a drug delivery system. The pha

Investigation of interactions between surface water and petroleum-type pollutants.

BACKGROUND, AIMS AND SCOPE: In oil spill investigations, one of the most important steps is a proper choice of approaches that imply an inve … alkanes and C19-C24 fatty acids in extract 4 is the formation of inclusion compounds with colloidal micelles formed between the oil contaminant's NSO-compounds and water. CONCLUSION: It was undoubtedly confirmed that there were specific differences in the compositions of the different extracts depending on the intensity of the interaction between the oil …

New concepts in bilirubin and jaundice: report of the Third International Bilirubin Workshop, April 6-8, 1995, Trieste, Italy.

The workshop covered three major areas: Unconjugated bilirubin (UCB) chemistry and physical chemistry; UCB transport and intracellular traff … o one UCB molecule; the other suggested that UCB binds to the nonpolar surface of helical bile salt micelles. (3) Structures were proposed for the varied calcium and copper bilirubinate salts formed at various pH values and cation/UCB ratios. (4) Studies of binding of UCB to human serum albumin (HSA) showed marked diminution of UCB-binding affinity as albu …

The π Configuration of the WWW Motif of a Short Trp-Rich Peptide Is Critical for Targeting Bacterial Membranes, Disrupting Preformed Biofilms, and Killing Methicillin-Resistant Staphylococcus aureus.

Tryptophan-rich peptides, being short and suitable for large-scale chemical synthesis, are attractive candidates for developing a new generation of antimicrobials to combat antibiotic-resistant bacteria (superbugs). Although there are numerous pictures of the membrane-bound structure of a single tryptophan (W), how multiple Trp amino acids assemble themselves and interact with bacterial membranes is poorly understood. This communication presents the three-dimensional structure of an eight-residue Trp-rich peptide (WWWLRKIW-NH2 with 50% W) determined by the improved two-dimensional nuclear magn

Celastrol nanomicelles attenuate cytokine secretion in macrophages and inhibit macrophage-induced corneal neovascularization in rats.

The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), …

Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development.

It is well known that neurodegenerative diseases' development and progression are accelerated due to oxidative stress and inflammation, whic … owing nanoscale delivery systems can be used to encapsulate polyphenols: nanocapsules, nanospheres, micelles, cyclodextrins, solid lipid nanoparticles, and liposomes. It results in great expectations for the wide-scale and effective use of polyphenols in the prevention of neurodegenerative diseases. Thus far, only natural polyphenols have been studied as n …

Developing oxidative stress-responsive neuroprotective nanotheranostic agents for the image-guided treatment of radiotherapy-induced brain injury.

RATIONALE: Radiotherapy-induced brain injury (RIBI) is a chronic side effect, that affects up to ~90% of brain tumor survivors treated with … after nanoparticle administration. RESULTS: Both polymers readily formed spherical nanoparticular micelles in aqueous milieu at low concentrations (~ 0.08 mg/mL), with comparable hydrodynamic diameters and zeta-potentials of 166 ± 51 nm and -2.52 ± 0.658 mV for P2a; and 183 ± 54 nm and -2.89 ± 1.58 mV for P2b. The activation kinetics of both nanoparticle …

Effects on mollicutes (wall-less bacteria) of synthetic peptides comprising a signal peptide or a membrane fusion peptide, and a nuclear localization sequence (NLS) -- a comparison with melittin.

In order to investigate the effect of primary amphipathic peptides on mollicutes (wall-less bacteria), we have synthesised five molecules (P1, P2, P3, JM123, and JM133) comprising a 16 to 18-residue hydrophobic sequence and the nuclear localization sequence (NLS) PKKKRKV of simian virus 40 large-T antigen, C-terminated by a cysteamide group. The hydrophobic cluster was in P1 the signal sequence of the heavy chain of Caiman crocodilus immunoglobulin G and in JM123 the fusion peptide of human immunodeficiency virus 1 glycoprotein gp41 in which phenylalanine7 was replaced by a tryptophan residue.

Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs.

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers t

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… Several studies have been reported on the co-delivery of curcumin using nano-sized micelles, as discussed below. Figure 3 Schematic diagram of micelles. … The average volume of the tumors treated with the co-loaded micelles was 4.7, 5.2, 5.4, 6.6-fold smaller when compared to curcumin-loaded micelles, paclitaxel-loaded micelles, free curcumin-paclitaxel, and 0.9% NaCl (control), respectively. …

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy.

Cancer therapies have advanced tremendously throughout the last decade, yet multiple factors still hinder the success of the different cancer therapeutics. The traditional therapeutic approach has been proven insufficient and lacking in the suppression of tumor growth. The simultaneous delivery of multiple small-molecule chemotherapeutic drugs and genes improves the effectiveness of each treatment, thus optimizing efficacy and improving synergistic effects. Nanomedicines integrating inorganic, lipid, and polymeric-based nanoparticles have been designed to regulate the spatiotemporal release of

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… The micelle dissociates, and then the drug separates by breaking down from monomers. Then, the polymer of the drug links inside the micelle, followed by a diffusional discharge from the micelle core nanocarrier ( Figure 3 ) [ 25 , 33 ]. … In cancer therapy, polymeric micelles, rather than lipid micelles, have been used in several studies as optimal delivery vehicles for different therapeutic agents. …

Стратегии лечения множественной миеломы, основанные на наномедицине.

Множественная миелома (ММ) принадлежит к гематологическим маньякам, и общее число случаев заболевания MM растет во всем мире. В течение последних нескольких десятилетий повышенное внимание уделялось развитию и патогенезу MM. Существенные изменения произошли также в парадигме лечения MM, включая протеаозные ингибиторы, иммуномодуляторы и анти CD38 моноклонные антитела, которые значительно улучшили выживание пациентов. Уделение все большего внимания наномедицине обусловлено ее способностью улучшить лечение MM за счет уменьшения системных побочных эффектов и создания возможностей для более точног

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… These nanosystems encompass a variety of structures including polymeric nanoparticles and polymer micelles. … Among polymer micelles, lipid core micelles form special groups, namely micelles formed by the coupling of soluble copolymers and lipids, such as polyethylene glycol phosphatidyl ethanolamine (PEG-PE) conjugates. 75 CFZ has been introduced into the market as a treatment option for refractory MM, and …

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc

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… Polymeric micelles Polymeric micelles are formed upon the self-assembly of amphiphilic polymers, with the hydrophobic portion of the polymer toward the core and the hydrophilic segments on the outer shell ( Figure 2 ). 13 The micelles are in the size range of 20–80 nm, suitable for the entrapment of … Additionally, PEG limits micelle interactions with other micelles (which could lead to aggregation) and proteins (opsonins). Several aspects of polymeric micelle-based delivery systems need to be addressed for further utilization in the clinical setting. …

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe

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… These micelles exhibited strong hydrophobic interactions between the double acyl chains, resulting in stable micelles with low critical micelle concentration values. … These micelles exhibited strong hydrophobic interactions between the double acyl chains, resulting in stable micelles with low critical micelle concentration values. …

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

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… These micelles increased the drug’s elimination half-life and biodistribution of vismodegib. Micelles made of cationic polymers may easily mix with nucleic acids and be taken up by target cells. … | micelles | Intravenous injection | In a siRNA sequence-specific way, intravenously administered hybrid micelles dramatically decreased the luciferase-based luminous signal from spontaneous PCA. …

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors.

Bone tumors are tumors that occur in the bone or its accessory tissues, including primary tumors and metastatic tumors. The main mechanism of bisphosphonate is to inhibit the resorption of destructive bone, inhibit the activity of osteoclasts and reduce the concentration of blood calcium. Therefore, bisphosphonates can be used for malignant hypercalcaemia, pain caused by osteolytic bone metastasis, prevention of osteolytic bone metastasis, multiple myeloma osteopathy, improving radiosensitivity and so on. However, the traditional administration of bisphosphonates can cause a series of adverse

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… Polymeric Micelles The polymer micelle has a hydrophobic interior core and a hydrophilic outer shell and has the characteristics of simple preparation, simultaneous loading of multiple drugs and easy surface modification. … The three-dimensional permeation experiments show that the polymer micelles developed by them can enter the tumor tissue, indicating that the micelles have a certain potential to become a tumor therapeutic drug delivery system. …

Biopharmaceutical and pharmacokinetic attributes to drive nanoformulations of small molecule tyrosine kinase inhibitors.

Buoyed by the discovery of small-molecule tyrosine kinase inhibitors (smTKIs), significant impact has been made in cancer chemotherapeutics. However, some of these agents still encounter off-target toxicities and suboptimal efficacies due to their inferior biopharmaceutical and/or pharmacokinetic properties. Almost all of these molecules exhibit significant inter- and intra-patient variations in plasma concentration-time profiles. Thus, therapeutic drug monitoring, dose adjustments and precision medicine are being contemplated by clinicians. Complex formulations or nanoformulation-based drug d

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… Although there are drawbacks to polymeric micelles, such as low stability in the gastrointestinal environment, numerous methods have been documented to increase the stability of the polymeric micelle. … It delivered the Dab and miR-200c. | At low dose, the development of tumors was reduced. | [94] Dasatinib (DAS) | Micelles: DAS was encapsulated in micelles. …

Advances in Drug Delivery and Biomaterials: Facts and Vision.

Drug delivery and biomaterials are different fields of science but, at the same time, are tightly related and intertwined. The 2018 CRS Italy Chapter Annual Workshop aims to explore recent advances in design and development in these areas. Many colleagues from Europe participated to the Workshop, stimulating the discussion. To foster the discussion on recent research and networking opportunities, especially among younger attendees, all poster-presenting authors were asked to provide a short talk. The very friendly and stimulating atmosphere allowed the attendees to explore new frontiers and ta

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… However, covalent crosslinking of micelles is considered to be of high importance to guarantee the stability of micelles in-vivo. Here, we introduced native chemical ligation (NCL) as a novel and straightforward method for covalent crosslinking of micelles in aqueous solution. … Aqueous solutions of these complementary polymers were mixed at 4 °C and rapidly heated to form either flower-like (ABA) or star-like (AB) micelles. Subsequently, native chemical ligation in the core of the micelles resulted in the stabilization of the micelles. …