Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

A review on the recent progress, opportunities, and challenges of 4D printing and bioprinting in regenerative medicine.

Four-dimensional (4 D) printing is a novel emerging technology, which can be defined as the ability of 3 D printed materials to change their form and functions. The term 'time' is added to 3 D printing as the fourth dimension, in which materials can respond to a stimulus after finishing the manufacturing process. 4 D printing provides more versatility in terms of size, shape, and structure after printing the construct. Complex material programmability, multi-material printing, and precise structure design are the essential requirements of 4 D printing systems. The utilization of stimuli-responsive polymers has increasingly taken the place of cell traction force-dependent methods and manual folding, offering a more advanced technique to affect a construct's adjusted shape transformation. The present review highlights the concept of 4 D printing and the responsive bioinks used in 4 D printing, such as water-responsive, pH-responsive, thermo-responsive, and light-responsive materials used in tissue regeneration. Cell traction force methods are described as well. Finally, this paper aims to introduce the limitations and future trends of 4 D printing in biomedical applications based on selected key references from the last decade.

Niosomes: a novel targeted drug delivery system for cancer.

Recently, nanotechnology is involved in various fields of science, of which medicine is one of the most obvious. The use of nanoparticles in the process of treating and diagnosing diseases has created a novel way of therapeutic strategies with effective mechanisms of action. Also, due to the remarkable progress of personalized medicine, the effort is to reduce the side effects of treatment paths as much as possible and to provide targeted treatments. Therefore, the targeted delivery of drugs is important in different diseases, especially in patients who receive combined drugs, because the delivery of different drug structures requires different systems so that there is no change in the drug and its effectiveness. Niosomes are polymeric nanoparticles that show favorable characteristics in drug delivery. In addition to biocompatibility and high absorption, these nanoparticles also provide the possibility of reducing the drug dosage and targeting the release of drugs, as well as the delivery of both hydrophilic and lipophilic drugs by Niosome vesicles. Since various factors such as components, preparation, and optimization methods are effective in the size and formation of niosomal structures, in this review, the characteristics related to niosome vesicles were first examined and then the in silico tools for designing, prediction, and optimization were explained. Finally, anticancer drugs delivered by niosomes were compared and discussed to be a suitable model for designing therapeutic strategies. In this research, it has been tried to examine all the aspects required for drug delivery engineering using niosomes and finally, by presenting clinical examples of the use of these nanocarriers in cancer, its clinical characteristics were also expressed.