Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.
- MeSH
- antigeny CD44 metabolismus MeSH
- antitumorózní látky * chemie MeSH
- irinotekan farmakologie MeSH
- kyselina hyaluronová chemie MeSH
- lignin MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory tračníku * farmakoterapie MeSH
- nanočástice * chemie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Lignin, the term commonly used in literature, represents a group of heterogeneous aromatic compounds of plant origin. Protolignin or lignin in the cell wall is entirely different from the commercially available technical lignin due to changes during the delignification process. In this paper, we assess the status of lignin valorization in terms of commercial products. We start with existing knowledge of the lignin/protolignin structure in its native form and move to the technical lignin from various sources. Special attention is given to the patents and lignin-based commercial products. We observed that the technical lignin-based commercial products utilize coarse properties of the technical lignin in marketed formulations. Additionally, the general principles of polymers chemistry and self-assembly are difficult to apply in lignin-based nanotechnology, and lignin-centric investigations must be carried out. The alternate upcoming approach is to develop lignin-centric or lignin first bio-refineries for high-value applications; however, that brings its own technological challenges. The assessment of the gap between lab-scale applications and lignin-based commercial products delineates the challenges lignin nanoparticles-based technologies must meet to be a commercially viable alternative.
Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.
- MeSH
- buněčné linie MeSH
- buňky A549 MeSH
- Drosophila melanogaster účinky léků MeSH
- HEK293 buňky MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lignin škodlivé účinky chemie MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nanočástice škodlivé účinky chemie MeSH
- nosiče léků škodlivé účinky chemie MeSH
- potkani Wistar MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Wood-based cellulose nanofibrils (CNF) offer an excellent scaffold for drug-delivery formulation development. However, toxicity and haemocompatibility of the drug carrier is always an important issue. In this study, toxicity-related issues of CNF were addressed. Different doses of CNF were orally administered to Drosophila and different tests like the developmental cycle, trypan blue exclusion assay, larva crawling assay, thermal sensitivity assay, cold sensitivity assay, larval light preference test, climbing behaviour, nitroblue tetrazolium (NBT) reduction assay, adult phenotype, and adult weight were conducted to observe the impact on its development and behaviour. A haemocompatibility assay was done on the blood taken from healthy Wistar rats. In Drosophila, the abnormalities in larval development and behaviour were observed in the behavioural assays. However, the cytotoxic effect could not be confirmed by the gut staining and level of reactive oxygen species. The larvae developed into an adult without any abnormality in the phenotype. The CNF did cause loss of weight in the adult flies and did not cause much toxicity within the body since there was no phenotypic defect. Hemolysis data also suggested that CNF was safe at lower doses, as the data was well within acceptable limits. All these results suggest that cellulose nanofibres have no significant cytotoxic effects on Drosophila. However, the developmental and behavioural abnormalities suggest that CNF may act as a behavioural teratogen.
- MeSH
- biokompatibilní materiály chemie toxicita MeSH
- celulosa chemie toxicita MeSH
- chování zvířat účinky léků MeSH
- dřevo chemie MeSH
- Drosophila melanogaster účinky léků MeSH
- nanovlákna chemie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A small, non-enveloped, obligatory parasite, Human papillomavirus (HPV) is known to be the cause of a range of malignancies. These entail benign infections like genital warts as well as malignant, life-threatening conditions such as cervical cancer. Since a very high mortality rate is associated with HPV caused cancers (cervical cancer is a 2nd leading cause of death caused due to cancer among women globally), there is an escalating need to understand and search for ways to combat such medical conditions. Under the same light, the given article provides an insight into the world of this versatile pathogen. Distinct aspects related to HPV have been discussed here. Emphasis has been laid upon the composition, function and assembly of capsid proteins (structural studies) and various genetic elements and their gene products (genomic studies). The essence of the mechanism behind the development of persistent infection and modes responsible for the transmission of the infectious particles has been briefly covered. Finally, the review outlines various infections and diseases caused by HPV with a major focus on their clinical and histological manifestations.
- MeSH
- genom virový * MeSH
- infekce papilomavirem virologie MeSH
- kondylomata akuminata virologie MeSH
- konformace proteinů MeSH
- lidé MeSH
- nádory děložního čípku virologie MeSH
- Papillomaviridae chemie genetika patogenita MeSH
- virové plášťové proteiny chemie genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Melanoma is the most serious form of skin cancer causing most of the skin cancer-related deaths. The incidence of melanoma has risen so dramatically over past few years that no other solid or blood malignancy comes close to it in terms of increased incidence. The main problem associated with the treatment of melanoma is low response rate to the existing treatment modalities, which in turn is due to the incomplete response by chemotherapeutic agents and inherent resistance of melanoma cells. MATERIALS AND METHODS: Conventional therapeutic strategies, as well as, recent literature on melanoma have been thoroughly studied. This review summarizes the base of anti-melanoma treatment with conventional chemotherapeutic drugs, followed by an account of recent studies which explored the potential of nanotechnology and newer strategies and agents in melanoma treatment. CONCLUSION: Although melanoma is curable if detected in its early localized form, metastatic melanoma continues to be a therapeutic challenge. Metastatic melanoma has a very poor prognosis and conventional therapies have not improved the outcomes of the treatment so far. For this reason, newer combinations of anti-melanoma drugs and newer strategies utilizing nanotechnology have been constantly explored.
- MeSH
- kombinovaná terapie škodlivé účinky metody MeSH
- lidé MeSH
- management nemoci MeSH
- melanom diagnóza etiologie mortalita terapie MeSH
- nádorové biomarkery MeSH
- nanomedicína metody MeSH
- nanotechnologie metody MeSH
- objevování léků MeSH
- standardní péče MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities.
- MeSH
- antigeny CD44 metabolismus MeSH
- antitumorózní látky chemie MeSH
- dakarbazin terapeutické užití MeSH
- fibroblastový růstový faktor 2 metabolismus MeSH
- inhibitory angiogeneze chemie MeSH
- inhibitory apoptózy chemie MeSH
- lidé MeSH
- liposomy chemie MeSH
- melanom metabolismus terapie MeSH
- nádory kůže terapie MeSH
- nanočástice chemie MeSH
- patologická angiogeneze MeSH
- proliferace buněk MeSH
- survivin MeSH
- teoretické modely MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Zinc oxide (ZnO) nanoparticles (NPs) are a promising platform for use in biomedical research, especially given their anticancer and antimicrobial activities. These activities are associated with the ability of ZnO NPs to generate reactive oxygen species (ROS) and induce apoptosis. In addition, ZnO NPs have been successfully exploited as drug carriers for loading and transporting drugs to target sites, thereby reducing unwanted toxicity and off-target effects, and resulting in amplified synergistic effects. Here, we discuss the synthesis and biomedical applications of ZnO NPs.
- MeSH
- lidé MeSH
- nanočástice * aplikace a dávkování chemie MeSH
- oxid zinečnatý * chemie farmakokinetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
