A5053577900- Dendrimers and Hyperbranched Polymers
- Click Chemistry and Applications
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Virology and Viral Diseases
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Cancer Research and Treatments
- Cancer therapeutics and mechanisms
- Nanoparticle-Based Drug Delivery
- Cancer Treatment and Pharmacology
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- vaccines and immunoinformatics approaches
- HIV/AIDS drug development and treatment
- Cancer Mechanisms and Therapy
Starpharma (Australia)
2005-2023
Monash University
2007
Background Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers highly branched nanoparticles being developed as microbicides. However, anti-HIV HSV structure-activity relationship dendrimers comprising benzyhydryl amide cores lysine branches, a comprehensive analysis their broad-spectrum activity mechanism action have not been published. Methods Findings with optimized against HIV-1 HSV-2 were...
Abstract Dual Bcl-2/Bcl-x L inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by tolerability issues. AZD4320, a potent dual inhibitor, has shown good efficacy however had dose limiting cardiovascular toxicity preclinical species, coupled with challenging physicochemical properties, which prevented its clinical development. Here, we describe the design development of AZD0466, drug-dendrimer conjugate, where...
Tritium-labeled poly-l-lysine dendrimers displaying 8 or 16 surface lysines have been capped with benzene sulfonate (BS), disulfonate (BDS), succinate (Succ) groups, and the intravenous pharmacokinetics disposition profiles of resulting (Lys8(BS)16, Lys16(BS)32, Lys16(BDS)32, Lys16(Succ)32) evaluated. Lys16(Succ)32 was rapidly removed from plasma primarily via renal elimination. Lys16(BS)32 Lys16(BDS)32 were opsonized, in more prolonged elimination kinetics increased uptake by liver. Data...
Abstract Docetaxel (Taxotere®) and cabazitaxel (Jevtana®) are mitotic inhibitors that function as effective cytotoxic agents widely used in many chemotherapy regimens. However, treatment with taxanes is limited by serious adverse toxicities, notably bone marrow toxicity (neutropenia, leukopenia anemia) hepatotoxicity. Taxanes poorly water soluble must be formulated surfactants such polysorbate, which can cause systemic events (e.g. anaphylaxis fluid retention) requiring predosing...
Abstract Irinotecan (Camptosar®) is a water-soluble prodrug of the potent topoisomerase I inhibitor SN-38 used clinically to treat multiple cancers. must be metabolized its active metabolite by carboxylesterases in hepatic and tumor cells. This metabolism humans inefficient with significant interpatient variability leads serious toxicities, notably diarrhea myelosuppression. The narrow therapeutic window irinotecan makes it an ideal candidate for improvement using dendrimer nanomedicine...
Starpharma focuses on the use of dendrimers as drugs in their own right – contrast to drug delivery vehicles or diagnostics. Dendrimers offer a unique platform for exploring chemical diversity nanoscale and production dendrimer libraries covering diverse array macromolecular structures can be used discovery development. One pharmaceutical application that is pursuing development microbicides prevention HIV sexually transmitted infections (STIs). This presentation will describe lead candidate...
Abstract Background: Development of targeted radiotheranostics for human epidermal growth factor receptor type 2 positive (HER2+) tumors has lagged advances made in other systems such as prostate-specific membrane antigen (PSMA) prostate cancer. Myelosuppression is a dose limiting toxicity clinical studies trastuzumab due to slow clearance this large radiotherapeutic from circulation. Conjugation chemotherapeutics taxanes and irinotecan/SN38 highly optimized dendrimer nanoparticles improves...
Abstract Background: Irinotecan is a topoisomerase 1 inhibitor pro-drug used to treat gastrointestinal (GI) cancers including as first line for colorectal cancer (CRC) part of the FOLFIRI plus monoclonal antibody (mAb) regimen, and pancreatic in FOLFIRINOX regimen. However, irinotecan causes severe dose-limiting side effects, diarrhea neutropenia. Starpharma has developed highly optimized polylysine dendrimer enhanced (DEP) nanoparticle conjugate active metabolite, SN38 (DEP or DEP...