Transethosomes: Cutting edge approach for drug permeation enhancement in transdermal drug delivery system.

The skin is a major route of drug administration. Despite the high surface area of the skin, drug delivery via the skin route is problematic due to its physiological obstacles. The formulation scientist has developed a vesicular system to enhance the skin's absorption of bioactive substances. Among numerous vesicular systems, concept of transethosomes (TEs) introduced in 2012 are being tested for drug delivery to the dermis. When transferosomes and ethosomes interact, TEs are produced. It consists of water, ethanol, phospholipids, and an edge activator. Ethanol and the edge activator increase the absorption of medication through the skin. In the presence of ethanol and an edge activator, skin permeability can increase. The advantages of TEs include increased patient compliance, bypassing first-pass metabolism, including non-toxic raw components, being a noninvasive method of drug delivery, being more stable, biocompatible, biodegradable, and administered in semisolid form. TEs can be produced through the use of hot, cold, mechanical dispersion, and conventional techniques. The morphology, shape, size, zeta potential, drug loading efficiency, vesicle yield, biophysical interactions, and stability of TEs define them. Recent studies reported successful transdermal distribution of antifungal, antiviral, anti-inflammatory, and cardiovascular bioactive while using ethosomes with significant deeper penetration in skin. The review extensively discussed various claims on TEs developed by researchers, patents, and marketed ethosomes. However, till today no patens being granted on TEs. There are still lingering difficulties related to ethanol-based TEs that require substantial research to fix.

Repurposing of Chemotherapeutics to Combat COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel strain of SARS coronavirus. The COVID-19 disease caused by this virus was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 mainly spreads through droplets sprayed by coughs or sneezes of the infected to a healthy person within the vicinity of 6 feet. It also spreads through asymptomatic carriers and has negative impact on the global economy, security and lives of people since 2019. Numerous lives have been lost to this viral infection; hence there is an emergency to build up a potent measure to combat SARS-CoV-2. In view of the non-availability of any drugs or vaccines at the time of its eruption, the existing antivirals, antibacterials, antimalarials, mucolytic agents and antipyretic paracetamol were used to treat the COVID-19 patients. Still there are no specific small molecule chemotherapeutics available to combat COVID-19 except for a few vaccines approved for emergency use only. Thus, the repurposing of chemotherapeutics with the potential to treat COVID-19 infected people is being used. The antiviral activity for COVID-19 and biochemical mechanisms of the repurposed drugs are being explored by the biological assay screening and structure-based in silico docking simulations. The present study describes the various US-FDA approved chemotherapeutics repositioned to combat COVID-19 along with their screening for biological activity, pharmacokinetic and pharmacodynamic evaluation.

Exploring the COVID-19 Potential Targets: Big Challenges to Quest Specific Treatment.

BACKGROUND: The novel strain SARS-CoV-2 of coronavirus diseases (COVID-19) became pandemic at the end of 2019 with an unprecedented global crisis by infecting around 11 million people in more than 200 countries. The condition has now been provoked by the demand, supply, and liquidity shocks that COVID-19 has attacked the lives of a vast population. OBJECTIVES: Researchers are therefore trying to encode and understand the viral genome sequence along with various potential targets to explore the transmission mechanism and the mode of treatment for COVID-19. The important structural proteins such as nucleocapsid protein (N), membrane protein (M), an envelope protein (E), and spike protein (S) related to COVID-19 are discussed in this manuscript. METHODS: The topology of these various targets has been explored utilizing structure-based design and crystallographic studies. RESULTS: The literature reported that the N-protein processes the viral genome to the host cell during replication. The "N-terminal domain" and "C-terminal domain" contribute towards localization in the endoplasmic region and dimerization respectively. The M protein determines the shape of coronavirus and also assists the S protein to integrate with the Golgi-endoplasmic region complex leading to the stabilization of the virion. The smallest hydrophobic viroporin termed "E" takes part in morphogenesis and pathogenesis during intracellular infection. The viral spike (S) protein attaches the cellular receptors and initiates virus-cell membrane fusions. The main protease in the proteolytic process during viral gene expression and replication has also been discussed. CONCLUSION: Currently, there is no permanent cure and treatment of COVID-19 hence researchers are repurposing a suitable combination of drugs including antiviral, antimalarial, antiparasitic, and antibacterial, hypertensive receptor blockers, immunosuppressants, anti-arthritis drugs, including ayurvedic formulations. In brief, it is justified that, for complete recovery, there is a need for deep and elaborate studies on genomic sequences and invading mechanisms in the host cell.