PEGylation

Hepatitis D virus (HDV) is an RNA subvirus that infects patients with co-existing hepatitis B virus (HBV) infections. HDV burden is estimated to be approximately 15-20 million people worldwide. Despite HDV severity, screening for HDV remains inadequate. HDV screening would benefit from a revamped approach that automatically reflexes testing when individuals are diagnosed with HBV if HBsAg-positive, to total anti-HDV, and then to quantitative HDV-RNA polymerase chain reaction (PCR) rather than only testing those at high risk sequentially...

BACKGROUND: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. METHODS: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B)...

Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability...

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies...

A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway...

Over the years, there has been significant interest in PEGylated lipid-based nanocarriers within the drug delivery field. The inevitable interplay between the nanocarriers and plasma protein plays a pivotal role in their in vivo biological fate. Understanding the factors influencing lipid-based nanocarrier and protein corona interactions is of paramount importance in the design and clinical translation of these nanocarriers. Herein, discoid-shaped lipid nanodiscs (sNDs) composed of different phospholipids with varied lipid tails and head groups were fabricated...

COVID-19 vaccines consisting of mRNA lipid nanoparticles (LNPs) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein antigen protected millions of people from severe disease; however, they must be stored frozen prior to use. The objective of this study was to evaluate the compatibility and stability of mRNA LNPs within a polymer-based film matrix. An optimized formulation of polymer base, glycerol, surfactants, and PEGylated lipid that prevents damage to the LNP due to physical changes during the film-forming process (osmotic stress, surface tension, spatial stress, and water loss) was identified...

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression. METHODS: Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers...

There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/Fe3 O4 -loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy...

Introduction The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. Aim We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12-<18 years at enrolment. Method PROTECT VIII was a multicentre, open-label study of previously treated males aged 12-65 years with severe haemophilia A (FVIII<1%)...

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and 1 H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates. For SAR study, all PEGylated 1,2,4-triazoles 5-8 performed potential anti-inflammatory activity on LPS-induced RAW 264...

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs. Functional upstream domain (FUD) tightly binds the N-terminal 70-kilodalton domain of FN that is crucial for FN assembly...

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility...

INTRODUCTION: Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon alpha (IFN-α, subtypes 2a and 2b) has been used for MF/SS since 1984, however its production was recently stopped and so the recombinant pegylated (PEG) form of IFN α-2a remains as single IFN alternative treatment, even though not approved for MF/SS. OBJECTIVE: To assess effectiveness and safety of PEG IFN α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in real world setting...

Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption...

Poly(ADP-ribose) polymerase inhibitors (PARPi) have been approved for once or twice daily oral use in the treatment of cancers with BRCA defects. However, for some patients, oral administration of PARPi may be impractical or intolerable, and a long-acting injectable formulation is desirable. We recently developed a long-acting PEGylated PARPi prodrug, PEG∼talazoparib (TLZ), which suppressed the growth of PARPi-sensitive tumors in mice for very long periods. However, the release rate of TLZ from the conjugate was too fast to be optimal in humans...

The development of nanoparticles could help to improve the efficacy/toxicity balance of drugs. This project aimed to develop liposomes and immunoliposomes using microfluidic mixing technology.Various formulation tests were carried out to obtain liposomes that met the established specifications. The liposomes were then characterized in terms of size, polydispersity index (PDI), docetaxel encapsulation rate and lamellarity. Antiproliferative activity was tested in human breast cancer models ranging from near-negative (MDA-MB-231), positive (MDA-MB-453) to HER2 positive...

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of vascular complications and a tendency to progress to myelofibrosis and acute leukaemia. ET patients have traditionally been stratified into two thrombosis risk categories based on age older than 60 years and a history of thrombosis. More recently, the revised IPSET-thrombosis scoring system, which accounts for the increased risk linked to the JAK2 mutation, has been incorporated into most expert recommendations...

PURPOSE: Proteins and peptides have secured a place as excellent therapeutic moieties on account of their high selectivity and efficacy. However due to oral absorption limitations, current formulations are mostly delivered parenterally. Oral delivery of peptides and proteins (PPs) can be considered the need of the hour due to the immense benefits of this route. This review aims to critically examine and summarize the innovations and mechanisms involved in oral delivery of peptide and protein drugs...

A 48-year-old female presented to the emergency department with severe fatigue. Admission laboratory test results were hemoglobin 6.6 g/dL, platelet count 287,000/μL, and white blood cell count 25,200/μL. Lactate dehydrogenase was elevated at 898 U/L, haptoglobin was markedly decreased (< 31 mg/dL), indirect bilirubin was elevated (5.3 mg/dL), and the absolute reticulocyte count was low at 0.0050/μL. A sample was sent to the immunohematology reference laboratory. The direct antiglobulin test immunoglobulin G was negative; C3 was 1+...