Search results for "Delivery"
showing 10 items of 1271 documents
Engineering approaches in siRNA delivery.
2017
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management ca…
Birth Mode-Related Differences in Gut Microbiota Colonization and Immune System Development.
2018
<b><i>Background:</i></b> The process of early gut colonization is extremely variable among individuals and is influenced by numerous factors. Among these, the mode of birth will strongly shape the early microbial exposure and immune environment of the neonate. <b><i>Summary:</i></b> Here, I review how the concomitant processes of microbiota and immune system development are altered by C-section delivery and the effects of such alterations on long-term health. <b><i>Key messages:</i></b> C-section delivery impinges on microbiota and immune system development through various means: (i) if labor is lacking, intrauterine i…
Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma
2020
Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of …
Controlled Transdermal Release of Antioxidant Ferulate by a Porous Sc(III) MOF
2020
Summary The Sc(III) MOF-type MFM-300(Sc) is demonstrated in this study to be stable under physiological conditions (PBS), biocompatible (to human skin cells), and an efficient drug carrier for the long-term controlled release (through human skin) of antioxidant ferulate. MFM-300(Sc) also preserves the antioxidant pharmacological effects of ferulate while enhancing the bio-preservation of dermal skin fibroblasts, during the delivery process. These discoveries pave the way toward the extended use of Sc(III)-based MOFs as drug delivery systems (DDSs).
Ticket to Ride: Targeting Proteins to Exosomes for Brain Delivery.
2017
Exosomes represent an attractive vehicle for the delivery of biomolecules. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here we report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes. We demonstrate that labeling of a target protein, Cre recombinase, with a WW tag leads to recognition by the L-domain-containing protein Ndfip1, resulting in ubiquitination and loading into exosomes. Our results show that Ndfip1 expression acts as a molecular switch for exosomal packaging of WW-Cre that can be suppressed using the exosome inhibitor GW4869. When taken up by floxed …
Dextran-based therapeutic nanoparticles for hepatic drug delivery.
2016
Aim: Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver. Materials & methods: DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake. Results: In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity. Conclusion: DNP are multifunctional liver-s…
Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles
2016
Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes…
Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
2017
Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors.…
Chemotherapeutic efficacy of curcumin and resveratrol against cancer: Chemoprevention, chemoprotection, drug synergism and clinical pharmacokinetics
2021
The frequent inefficiency of conventional cancer therapies due to drug resistance, non-targeted drug delivery, chemotherapy-associated toxic side effects turned the focus to bioactive phytochemicals. In this context, curcumin and resveratrol have emerged as potent chemopreventive and chemoprotective compounds modulating apoptotic and autophagic cell death pathways in cancer in vitro and in vivo. As synergistic agents in combination with clinically established anticancer drugs, the enhanced anticancer activity at reduced chemotherapy-associated toxicity towards normal organs can be explained by improved pharmacokinetics, pharmacodynamics, bioavailability and metabolism. With promising precli…
Dosimetric Impact of Interfractional Variations in Prostate Cancer Radiotherapy—Implications for Imaging Frequency and Treatment Adaptation
2019
Background and purpose: To analyze deviations of the applied from the planned doses on a voxel-by-voxel basis for definitive prostate cancer radiotherapy depending on anatomic variations and imaging frequency. Materials and methods: Daily in-room CT imaging was performed in treatment position for 10 patients with prostate cancer undergoing intensity-modulated radiotherapy (340 fraction CTs). Applied fraction doses were recalculated on daily images, and voxel-wise dose accumulation was performed using a deformable registration algorithm. For weekly imaging, weekly position correction vectors were derived and used to rigidly register daily scans of that week to the planning CT scan prior to d…