A Review on DNA Vaccines in Pre-Clinical Trials Against SARS-CoV-2

COVID 19 Pandemic is caused by the viral pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Scientific fraternity worldwide swiftly developed various types of vaccines for the prevention and as mitigation measures for curbing the pandemic. Traditional inactivated vaccines, mRNA vaccines (protein subunits such as spike proteins), and viral vector vaccines (non-replicating vectors with protein subunits) have been approved by World Health Organisation (WHO) for emergency use. The emergence of many mutated variants has been a worrying factor in the fight against the pandemic. There has been continuous research in the quest for more therapeutics, especially vaccines to curb and stop the pandemic. According to WHO, there are 194 vaccines in pre-clinical trials belonging to various types out of which sixteen is DNA vaccines. In this review, we have discussed the advantages and disadvantages of the DNA vaccines for Covid - 19. This article tried to explore the available information on DNA vaccines and their current status against Covid – 19 which are in pre-clinical trials

Nanogels as novel drug nanocarriers for CNS drug delivery

Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties.Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats.Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ’s neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed.Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (−7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties.Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders

Pharmacological Management of Tuberculosis, Challenges, and Potential Strategies

Tuberculosis (TB) is an infection caused by the pathogen Mycobacterium tuberculosis. The disease causes around 2 million deaths worldwide, and incidences of drug resistance only makes increases the number. The most vulnerable victims of TB infections are children and human immunodeficiency virus (HIV) patients. TB and HIV co-infections can be deadly in AIDS sufferers, as the immune system is not able to combat TB infections, hence worsening the infection. Common drugs to treat TB are available in the market, first-line drugs such as isoniazid and rifamycin are broad-spectrum drugs. Second-line antibiotics such as fluoroquinolones are also available. In this review, the mechanisms of action of TB drugs are briefly discussed, as wells as the respective resistant mechanisms of M. tuberculosis against these drugs. An updated treatment regime for TB management using bedaquiline, pretomanid and linezolid was also discussed, which shows 90% therapeutic efficacy against highly drug-resistant tuberculosis cases. Furthermore, novel strategies such as nanoparticle-conjugated TB drugs can improve drug delivery, TB drug efficiency while reducing side effects. However, importance on patient compliance to the treatment regime is still the most crucial part of TB management, hence initiatives can be put to improve patient awareness and education

Deciphering synsepalum dulcificum as an arising phytotherapy agent: Background, phytochemical and pharmacological properties with associated molecular mechanisms

Medicinal plants with less side effects are paramount important for humankind to cure various ailments as compared to newly developed allopathic medicines. Synsepalum dulcificum Daniell (Sapotaceae), is well known as miracle fruits due to its distinctive taste-modifying property. This review aimed to discuss its recent reported pharmacological properties and associated molecular mechanisms as a novel phytotherapy agent. In addition, background, phytochemical analysis and toxicological studies were also discussed as the foundation and added values for this review. It was discovered that S. dulcificum is endowed with various classes of phytochemicals, such as flavonoids, tannins, alkaloids and saponins. This review ravelled that S. dulcificum is a potent medicinal plant associated with antioxidant, antidiabetic, antimicrobial, anticancer, anti-hyperuricemic, hepatoprotective, anti-hyperlipidaemic, and anticonvulsant activities, with less toxicity shown. Future research may explore further the corresponding phytochemicals, associated molecular mechanisms, toxicological and pharmacokinetic profile before subjecting to clinical testing

Fabrication of Tizanidine Loaded Patches Using Flaxseed Oil and Coriander Oil as a Penetration Enhancer for Transdermal Delivery

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs

Deciphering Synsepalum dulcificum as an arising phytotherapy agent : background, phytochemical and pharmacological properties with associated molecular mechanisms

Medicinal plants with less side effects are paramount important for humankind to cure various ailments as compared to newly developed allopathic medicines. Synsepalum dulcificum Daniell (Sapotaceae), is well known as miracle fruits due to its distinctive taste-modifying property. This review aimed to discuss its recent reported pharmacological properties and associated molecular mechanisms as a novel phytotherapy agent. In addition, background, phytochemical analysis and toxicological studies were also discussed as the foundation and added values for this review. It was discovered that S. dulcificum is endowed with various classes of phytochemicals, such as flavonoids, tannins, alkaloids and saponins. This review ravelled that S. dulcificum is a potent medicinal plant associated with antioxidant, antidiabetic, antimicrobial, anticancer, anti-hyperuricemic, hepatoprotective, anti-hyperlipidaemic, and anticonvulsant activities, with less toxicity shown. Future research may explore further the corresponding phytochemicals, associated molecular mechanisms, toxicological and pharmacokinetic profile before subjecting to clinical testing

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus

Evaluation of Antitumor Efficacy of Chitosan-Tamarind Gum Polysaccharide Polyelectrolyte Complex Stabilized Nanoparticles of Simvastatin

Purpose: The present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines. Materials and Methods: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32 ) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles. Results: Formulated nanoparticles showed high entrapment efficiency (67.19±0.42–83.36 ±0.23%) and small size (53.3–383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker–Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies. Conclusion: The present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems

Determination of Temperature-Dependent Coefficients of Viscosity and Surface Tension of Tamarind Seeds (Tamarindus indica L.) Polymer

The rheological properties of tamarind seed polymer are characterized for its possible commercialization in the food and pharmaceutical industry. Seed polymer was extracted using water as a solvent and ethyl alcohol as a precipitating agent. The temperature’s effect on the rheological behavior of the polymeric solution was studied. In addition to this, the temperature coefficient, viscosity, surface tension, activation energy, Gibbs free energy, Reynolds number, and entropy of fusion were calculated by using the Arrhenius, Gibbs–Helmholtz, Frenkel–Eyring, and Eotvos equations, respectively. The activation energy of the gum was found to be 20.46 ± 1.06 kJ/mol. Changes in entropy and enthalpy were found to be 23.66 ± 0.97 and −0.10 ± 0.01 kJ/mol, respectively. The calculated amount of entropy of fusion was found to be 0.88 kJ/mol. A considerable decrease in apparent viscosity and surface tension was produced when the temperature was raised. The present study concludes that the tamarind seed polymer solution is less sensitive to temperature change in comparison to Albzia lebbac gum, Ficus glumosa gum and A. marcocarpa gum. This study also concludes that the attainment of the transition state of viscous flow for tamarind seed gum is accompanied by bond breaking. The excellent physicochemical properties of tamarind seed polymers make them promising excipients for future drug formulation and make their application in the food and cosmetics industry possibl