Drug-based therapeutic strategies for COVID-19-infected patients and their challenges.

Emerging epidemic-prone diseases have introduced numerous health and economic challenges in recent years. Given current knowledge of COVID-19, herd immunity through vaccines alone is unlikely. In addition, vaccination of the global population is an ongoing challenge. Besides, the questions regarding the prevalence and the timing of immunization are still under investigation. Therefore, medical treatment remains essential in the management of COVID-19. Herein, recent advances from beginning observations of COVID-19 outbreak to an understanding of the essential factors contributing to the spread and transmission of COVID-19 and its treatment are reviewed. Furthermore, an in-depth discussion on the epidemiological aspects, clinical symptoms and most efficient medical treatment strategies to mitigate the mortality and spread rates of COVID-19 is presented.

Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer.

5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.

Double domain polyethylenimine-based nanoparticles for integrin receptor mediated delivery of plasmid DNA.

The objective of the present study is to conjugate L-thyroxine PEI derivative onto another PEI to compensate the amine content of the whole structure which has been utilized for the ligand conjugation. Since αvß3 integrin receptors are over-expressed on cancer cells and there is binding site for L-thyroxine on these receptors, PEI conjugation by L-thyroxine along with restoring the PEI amine content might be an efficient strategy for targeted delivery using polymeric nanoparticles. The results demonstrated the ability of the PEI conjugate in the formation of nanoparticles with the size of around 210 nm with higher buffering capacity. The conjugated PEI derivative increased the transfection efficiency in the cell lines over-expressing integrin by up to two folds higher than unmodified PEI, whereas in the cell lines lacking the integrin receptors there was no ligand conjugation-associated difference in gene transfer ability. The specificity of transfection demonstrated the delivery of plasmid DNA through integrin receptors. Also, the results of in vivo imaging of the polyplexes revealed that 99mTc-labeled PEI/plasmid DNA complexes accumulated in kidney and bladder 4 h post injection. Therefore, this PEI derivative could be considered as an efficient targeted delivery system for plasmid DNA.

Tetraiodothyroacetic acid-conjugated polyethylenimine for integrin receptor mediated delivery of the plasmid encoding IL-12 gene.

Targeted delivery by polymer-based nanoparticles has been considered as an efficient approach to transfer genetic materials into cells. Considering the over expression of integrin αVß3 receptor on tumor cells and the presence of the binding site for tetraiodothyroacetic acid (tetrac) on integrin receptor, we hypothesized that the conjugation of tetrac to polyethylenimine (PEI) might be an effective strategy for pDNA delivery into the cells over-expressing integrins on their surfaces. In order to test the hypothesis, tetrac conjugated PEI/plasmid DNA complexes were prepared and their ability in the delivery of plasmid encoding IL-12 gene was investigated. Moreover, the conjugates were characterized with respect to plasmid DNA condensation ability, particle size and zeta potential as well as cell-induced toxicity and plasmid protection against DNase degradation. The results demonstrated that tetrac conjugated derivatives of PEI were able to condense the plasmid and protect it against enzyme degradation. The results of dynamic light scattering (DLS) and atomic force microscopy (AFM) revealed that the formed nanoparticles were in the size range of 85-125nm. The highest level of IL-12 gene expression was achieved by terac-conjugated PEIs at the carrier to plasmid ratio of 8 where they could increase the level of gene expression up to 4 fold in the cell lines over-expressing integrin αVß3 receptor whereas no increase in the level of IL-12 expression in the cell lines lacking integrin receptors was observed. Also, the results of the competitive inhibition of the receptors demonstrated the specificity of transfection for the cells over expressing αvß3 receptor. On the other hand, tetrac conjugation of PEI significantly reduced the polymer-induced apoptotic effects. The results obtained in this investigation suggest the potential of tetrac as a small molecule mimicking the binding properties of integrin binding peptides (e.g., RGD) for targeted gene delivery.