Biotinylated HPMA Centered Polymeric Nanoparticles for Bortezomib Delivery

Publication date: Available online 22 February 2020Source: International Journal of PharmaceuticsAuthor(s): Sarita Rani, Rakesh K. Sahoo, Kartik T. Nakhate, Ajazuddin, Umesh GuptaAbstractBortezomib (BTZ) is a proteasome inhibitor as approved by US FDA for the treatment of multiple myeloma. It exhibits significant anti-cancer properties including against solid tumors; but lacks aqueous solubility, chemical stability which hinders its successful formulation development. The present study is an attempt to deliver BTZ using N-(2-hydroxypropyl) methacrylamide (HPMA) based copolymeric conjugates and biotinylated PNPs in an effective manner. Study describes a systematic synthetic pathway to synthesize functional polymeric conjugates such as HPMA-Biotin (HP-BT) HPMA-Polylactic acid (HPLA) and HPMA-PLA-Biotin (HPLA-BT) followed by exhaustive characterization both spectroscopically and microscopically. Our strategy yielded polymeric nanoparticles (PNPs) of narrow size range of 199.7±1.32 nm. Release studies were performed at pH 7.4 and 5.6. PNPs were 2-folds less hemolytic (p
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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In this study, we sought to investigate whether scutellarin (STN), a flavonoid, could reduce MM progression, mitigate chemoresistance of MM cells to bortezomib (BTB), and cause MM cell apoptosis in a xenograft mouse model of MM. Epigenetic signalling plays a main role in the modulation of various pathways involved in multiple myeloma progression. At the outset, mechanistic analyses of the MM pathways indicated that key epigenetic molecules including HDAC1/3 and miR-34a were up-modulated and down-modulated respectively, in the MM mice. Besides, the downstream signalling analysis of miR-34a depicted that the c-Met/AKT/mTOR p...
Source: International Journal of Clinical and Experimental Pathology - Category: Pathology Authors: Tags: Int J Clin Exp Pathol Source Type: research
ojo Fujii Recent cancer treatment modalities have been intensively focused on immunotherapy. The success of chimeric antigen receptor T cell therapy for treatment of refractory B cell acute lymphoblastic leukemia has pushed forward research on hematological malignancies. Among the effector types of innate lymphocytes, natural killer (NK) cells show great importance in immune surveillance against infectious and tumor diseases. Particularly, the role of NK cells has been argued in either elimination of target tumor cells or escape of tumor cells from immune surveillance. Therefore, an NK cell activation approach has b...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
(Worldwide Cancer Research) Researchers at the VU University Medical Center in the Netherlands have tested a new drug in patient samples and mice with multiple myeloma and discovered that it was effective even in advanced disease -- a point when many patients currently run out of options. These promising results could pave the way for the new drug to be tested in patients.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
CONCLUSIONS: BM infiltrating T cell subsets, specifically Treg and PD-1 expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies. PMID: 32220887 [PubMed - as supplied by publisher]
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ntonino Neri Elisa Taiana The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies. Transcripto...
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Abstract Metastatic bone disease (MBD) is common-it is detected in up to 65-75% of patients with breast or prostate cancer, in over 35% of patients with lung cancer; and almost all patients with symptomatic multiple myeloma have focal lesions or a diffuse bone marrow infiltration. Metastatic bone disease can cause a variety of symptoms and is often associated with a poorer prognosis, with high social and health-care costs. Population-based cohort studies confirm significantly increased health-care utilization costs in patients presenting with cancer with MBD compared with those without MBD. The prol...
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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