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OBJECTIVE: The study was aimed at formulating temozolomide (TMZ) loaded gelatin nanoparticles (GNPs) encapsulated into polyvinyl alcohol (PVA) nanofibers (TMZ-GNPs-PVA NFs) as the nano-in-nanofiber delivery system. The secondary objective was to explore the sustained releasing ability of this system and to assess its enhanced cellular uptake against U87MG glioma cells in vitro. SIGNIFICANCE: Nano-in-nanofibers are the emerging drug delivery systems for treating a wide range of diseases including cancers as they overcome the challenges experienced by nanoparticles and nanofibers alone. METHODS: The drug-loaded GNPs were formulated by one-step desolvation method. The Design of Experiments (DoE) was used to optimize nanoparticle size and entrapment efficiency. The optimized drug-loaded nanoparticles were then encapsulated within nanofibers using blend electrospinning technique. The U87MG glioma cells were used to investigate the uptake of the formulation. RESULTS: A 32 factorial design was used to optimize the mean particle size (145.7 nm) and entrapment efficiency (87.6%) of the TMZ-loaded GNPs which were subsequently ingrained into PVA nanofibers by electrospinning technique. The delivery system achieved a sustained drug release for up to seven days (in vitro). The SEM results ensured that the expected nano-in-nanofiber delivery system was achieved. The uptake of TMZ-GNPs-PVA NFs by cells was increased by a factor of 1.964 compared to that of the pure drug. CONCLUSION: The nano-in-nanofiber drug delivery system is a potentially useful therapeutic strategy for the management of glioblastoma multiforme.

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Glioblastoma multiforme (GBM) is one of the most lethal cancer due to poor diagnosis and rapid resistance developed towards the drug. Genes associated to cancer-related overexpression of proteins, enzymes, and receptors can be suppressed using an RNA silencing technique. This assists in obtaining tumour targetability, resulting in less harm caused to the surrounding healthy cells. RNA interference (RNAi) has scientific basis for providing potential therapeutic applications in improving GBM treatment. However, the therapeutic application of RNAi is challenging due to its poor permeability across blood-brain barrier (BBB). Nanobiotechnology has evolved the use of nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, dendrimers, quantum dots and other nanostructures in encasing the RNAi entities like siRNA and miRNA. The review highlights the role of these carriers in encasing siRNA and miRNA and promising therapy in delivering them to the glioma cells.

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Nanofibers are cutting-edge drug delivery systems that are being utilised to treat a variety of ailments. Nanofibers are mostly woven by electrospinning techniques that are majorly used in drug delivery, wound dressing, tissue engineering, sensors, etc. They have several limitations that can be addressed by developing nano-in-nano delivery techniques. Nanoparticles are incorporated into nanofibers in these nano-in-nano systems. They offer a lot of benefits over other nanosystems, including the ability to shield drugs from physical deterioration, the ability to provide prolonged drug release, high surface area to volume ratio, increased drug loading capacity and the potential to be employed in critical conditions such as cancer. These nanoparticles can be encapsulated, entrapped, or adsorbed onto nanofibers in a variety of ways. To include nanosystems into nanofibers, a variety of materials and different kinds of nanoparticles can be used. The present review gives an insight to the applications of nano - in - nano drug delivery system for different diseases/disorders. The review also brings forward the current state of these novel delivery systems along with future perspectives.

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Glioblastoma multiforme (GBM) is abnormal cell proliferation of glial cells. GBM is the grade IV glioma brain cancer which is life-threatening to many individuals affected by this cancer. The DNA alkylating agent Temozolomide (TMZ) has the distinctiveness of being FDA approved anticancer drug for the first line treatment for GBM. However, treatment of GBM still remains a challenge. This is attributed to TMZ's toxic nature, severe side effects, and fast degradation in vivo. In addition, the lack of targeting ability increases the chances of systemic toxicities. A nano enabled targeted delivery system not only improves the efficiency of TMZ by making it cross the blood brain barrier, have specificity to target, but also reduces toxicity to healthy tissues. Over the last decade the significant advances in the area of nanotechnology applied to medicine have developed many multifunctional therapeutics. In this context, the present review article comprehends the significant progress in the field of TMZ loaded nanocarriers showing promise for futuristic nanomedicine therapies in treating GBM.

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Occupational health literature links stressful working conditions with cardiovascular and other chronic diseases, injuries, and psychological distress. We conducted individual interviews with employee assistance professionals (EAPs) to understand opportunities and barriers for EAPs to address job stress through organization level interventions. EAPs described their primary role as assisting individual employees versus designing company wide interventions. The most salient barriers to organization level interventions cited were lack of access to company management and (for contracted EAPs) perceptions of contract vulnerability. Education about workplace stress interventions may be most effectively directed at EAPs who are already integrated with company level work groups.

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Workplace stress is strongly associated with health problems, including cardiovascular disease. The occupational health field is developing partnerships with a variety of health professions to prevent and address job stress at the organizational level. A review of literature for and about employee assistance professionals was conducted to explore their perspectives on these issues. Results show high awareness regarding the health effects of job stress and a wide range of approaches to address this problem. EAPs appear to be a potential strong partner in efforts to prevent workplace stress, but face obstacles to intervening at the level of the work environment.

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