Investigation of chitosan nanoparticles as a carrier of therapeutic agents: Bio-mechanical effects on cancer cell line, applications in delivery of gene and chemotherapeutic agents

Chitosan derivatives are used in drug and gene delivery applications due to their outstanding biological features. Chitosan, owing to its unique chemical structure, can fabricate nanoparticles through simple nanofabrication methods using various crosslinkers. There are several exclusive characteristics including the ability of forming conjugates with negatively charged materials such as DNA, siRNA and alginate, anticancer characteristics, relatively long blood circulation period as well as low uptake through reticulo endothelial system (RES) and mucoadhesion that make chitosan derivatives as a promising class of carriers for therapeutic delivery applications. <br>    Despite the increasing trend of applications for chitosan nanoparticles, in different research works these nanoparticles mainly were studied only from one or two particular perspectives. there are a limited number of comprehensive studies from different perspectives regarding pharmaceutical applications of the chitosan nanoparticles for cancer treatment. In addition, there is lack of study on biomechanical effects of the chitosan-anti cancer drug conjugates on cancerous cells. <br>    The aim of this PhD research program is to in-depth investigation of chitosan nanoparticles from different perspectives for pharmaceutical applications especially in cancer therapy (e.g. method of fabrication, physiological-responsive derivatives, biomechanical effects and development its prolonged release characteristics). In the first part of this project, a new redox responsive nanostructure based on chitosan derivative was designed, synthesized and employed for gene delivery application. In the second part, we demonstrated an efficient tumor targeting chitosan-based nanoparticulate drug delivery system, designed for the oral administration of cancer therapeutic agents. For the first time, a dual microfluidic platform was employed to synthesize nanocarriers with highly pH-tunable core-shell structure. In the third part, we investigated the effects of albendazole encapsulated chitosan nanoparticles on the mechanical behaviour of the cytoskeleton of SW48 (Human colon adenocarcinoma cell line. The anticancer efficacy of the chitosan-drug conjugates as well as its selectivity towards the cancer cells were examined. In the final part of this project, a recently-developed gel aspiration-ejection fabrication technique of dense collagen hydrogel (DNS CG) and chitosan-sulfated cyclodextrin (CS-SCD) conjugation was used to design hierarchical drug delivery system for prolonged controlled release of therapeutic agents

Herbal extract incorporated chitosan based nanofibers as a new strategy for smart anticancer drug delivery system: an in vitro model

Objective: Despite the anticancer effect of Berberine (BBR), low aqueous solubility and poor gastrointestinal absorption can make its therapeutic usage difficult. However, chitosan/polyethylene oxide (CH/PEO) nanofibers scaffold eliminate this problem. This study has been conducted to recognize CH/PEO/BBR nanofibers effect on cancer cell lines. Material and Methods: CH/PEO solution was prepared at different ratios for achieving optimal nanofibers. CH/PEO/BBR nanofibers were provided via electrospinning. Internal structure and 3-D morphology of fibers were studied using TEM and AFM, respectively. Functional groups were analyzed by a Fourier Transform Infrared (FTIR) spectroscopic device. The characterization of electrospun nanofibers was done by SEM. BBR released from nanoscaffolds was detected within 2 weeks by a UV-Visible device. The growth and proliferation of human breast cancer cell lines (MDA-MB-468, BT474 and MCF7), human HeLa cervical cancer cells and fibroblast cells in cultured medium were investigated by an inverted microscope. The cytotoxic effect of CH/PEO/BBR nanofibers against mentioned cell lines was characterized by MTT assay. Statistical analysis was done by SPSS-18 software. p<0.05 was considered as significant. Results: Nanoscaffolds containing 0.5-20 wt.% BBR concentrations inhibited cell growth compared to the control group in HeLa, BT474, MCF7 and MDA-MB-468 cell lines. The cell viability of cancer cell lines was significantly decreased after exposure with CH/PEO/BBR in a time dependent manner (HeLa, BT474, MCF7 (p=0.000) and MDA-MB-468 (p=0.001)). Conclusions: Our results suggested that CH/PEO/BBR nanofiber has the potential to be developed as co-chemotherapeutic agent for human breast and cervical cancer therapy. However, its molecular mechanisms need to be further explored

HSP90 and Co-chaperones: Impact on Tumor Progression and Prospects for Molecular-Targeted Cancer Therapy

Heat shock protein 90 (HSP90), a highly and unique chaperone, presents as a double-edged sword. It plays an essential role in many physiological and pathological processes, including tumor development. The current review highlights a recent understanding of the roles of HSP90 in molecular mechanisms underlying cancer survival and progression. HSP90 and its client proteins through the regulation of oncoproteins including signaling proteins, receptors, and transcriptional factors involved in tumorigenesis. It also has potential clinical application as diagnostic and prognostic biomarkers for assessing cancer progression. In this way, using HSP90 to develop new anticancer therapeutic agents including HSP90 inhibitors, anti-HSP90 antibody, and HSP90-based vaccines has been promising. © 2020, © 2020 Taylor & Francis Group, LLC

Emerging cytokines in allergic airway inflammation: A genetic update

Purpose: We aim to discuss the current status of knowledge on the role of recently identified cytokines in airway hyper responsiveness as well as the genetic predisposition conferred by their coding genes to asthma. Methods: We focused on three cytokines and their coding genes,-IL-9, IL-17, and IL-22, and conducted a narrative review of all the relevant publications known to the authors. Results: A great body of evidence regarding the involvement of these three cytokines in asthma was discussed and interpreted. These range from studies on the murine models of asthma to clinical and human genetic approaches. Despite the large amounts of information existing on the genetics of IL-9 and IL-17, there is a lacking trend towards the IL-22 genetic studies in asthma. Conclusion: The emergence of new classes of T-helper effector cells and their cytokines has led to a change in our understanding of asthma pathogenesis. This has created both new opportunities and challenges for researchers involved in this field, and is likely to result in improvements and progress in identifying and developing novel therapeutic measures and innovative treatments for asthma. © 2016 Bentham Science Publishers

Preparation and characterization of polylactic-co-glycolic acid/insulin nanoparticles encapsulated in methacrylate coated gelatin with sustained release for specific medical applications

This study aimed to examine the possibility of using insulin orally with gelatin encapsulation to enhance the usefulness of the drug and increase the lifespan of insulin in the body using polylactic-co-glycolic acid (PLGA) nanoparticles alongside gelatin encapsulation. In this regard, PLGA was synthesized via ring opening polymerization, and PLGA/insulin nanoparticles were prepared by a modified emulsification�diffusion process. The resulting nanoparticles with various amounts of insulin were fully characterized using FTIR, DSC, DLS, zeta potential, SEM, and glucose uptake methods, with results indicating the interaction between the insulin and PLGA. The process efficiency of encapsulation was higher than 92, while the encapsulation efficiency of nanoparticles, based on an insulin content of 20 to 40, was optimized at 93. According to the thermal studies, the PLGA encapsulation increases the thermal stability of the insulin. The morphological studies showed the fine dispersion of insulin in the PLGA matrix, which we further confirmed by the Kjeldahl method. According to the release studies and kinetics, in-vitro degradation, and particle size analysis, the sample loaded with 30 insulin showed optimum overall properties, and thus it was encapsulated with gelatin followed by coating with aqueous methacrylate coating. Release studies at pH values of 3 and 7.4, alongside the Kjeldahl method and standard dissolution test at pH 5.5, and glucose uptake assay tests clearly showed the capsules featured 3�4 h biodegradation resistance at a lower pH along with the sustained release, making these gelatin-encapsulated nanoparticles promising alternatives for oral applications. (Figure presented.). © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group