An Insight on Novel Approaches & Perspectives for Gastro-Retentive Drug Delivery Systems.

The conventional oral drug delivery systems face a lot of difficulties in the gastrointestinal tract, such as inappropriate drug release and reduction in the efficacy of the doses, which makes this system less susceptible to the delivery of drug formulation. For the enhancement of therapeutic efficacy and bioavailability of the drug, many efforts have been made. The drug candidates which are not stable at alkaline pH and soluble in acidic medium were selected to increase their therapeutic effectiveness through gastro retentive drug delivery systems (GRDDS). This article discusses various factors which alter the gastro retention time (GRT) of the gastro retentive drug delivery system in the stomach and intestine (duodenum). It emphasizes on the novel approaches made for the delivery and release of drugs with the use of magnetic systems, floating (low-density) systems, super porous hydrogels, raft systems, mucoadhesive systems, high-density systems and expandable systems. Along with the applications, the key aspects of in vivo, in vitro & clinical studies in different approaches to GRDDS have been addressed. In addition, future perspectives have been summarized to reduce gastric transit time in fasting and fed conditions.

Monkeypox infection: The past, present, and future.

Monkeypox is a zoonotic illness caused by the monkeypox virus (MPXV) that has a similar etiology to smallpox. The first case of monkeypox was reported in Western and Central Africa in 1971, and in 2003, there was an outbreak of monkeypox viruses outside Africa. According to the World Health Organization (WHO) and Center for Disease Control and Prevention (CDC), monkeypox is transmitted through direct contact with infected animals or persons exposed to infectious sores, scabs, or body fluids. Also, intimate contact between people during sex, kissing, cuddling, or touching parts of the body can result in the spreading of this disease. The use of the smallpox vaccine against monkeypox has several challenges and hence anti-virals such as cidofovir, brincidofovir, and tecovirimat have been used for the symptomatic relief of patients and reversing the lesion formation on the skin. Despite the recent outbreak of monkeypox most especially in hitherto non-endemic countries, there is still a lack of definitive treatment for monkeypox. In the present review, emphasis was focused on etiopathology, transmission, currently available therapeutic agents, and future targets that could be explored to halt the progression of monkeypox. From our review we can postulate that owing to the lack of a definitive cure to this reemerging disorder, there is a need for general awareness about the transmission as well as to develop appropriate diagnostic procedures, immunizations, and antiviral medication.

Mitochondrial dynamics related neurovascular approaches in cerebral ischemic injury.

Mitochondria are double-membrane organelles that provide the majority of a cell's energy. Furthermore, mitochondria are involved in various cellular biological activities, including calcium signalling, reactive oxygen species production, apoptosis, cell development, and the cell cycle. Mitochondrial dysfunction is seen in various neurological conditions involving acute and chronic neural injury, including neurodegenerative diseases, hypoxia-induced brain injury, and ischemia. This review made a significant contribution to the explanation of the idea that mitochondria would both be critical targets of ischemia-induced processes, including intracellular calcium elevation and reactive oxygen species and essential sites for determining cell viability loss. As a result, it's not unexpected that attempts to prevent I/R damage have focused on mitochondria. Drugs such as vatiquinone, vitexin, dexprmipexole, baicalin, nobiletin, via promoting mitochondrial activities, can be used in future studies for protecting the brain from ischemia injury. This review summarizes mitochondrial pathways, i.e., Bad, Drp-1, JNK/caspase-3, MAPK-ERK, p53, Wnt/ß-Catenin, that contribute to disease progression. We have précised the potential regulatory role of miRNA-mitochondrial dynamics in cerebral ischemic-reperfusion injury and associated molecular mechanisms; also provide insight into the potential therapies for cerebral injury-induced injuries.

Demethyleneberberine: A possible treatment for Huntington's disease.

Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported.