Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

An Overview of Contemporary and Future Therapeutic Strategies for Scalp Psoriasis.

Scalp psoriasis is a common manifestation of psoriasis that significantly impacts a patient's quality of life. About 80% of cases of psoriasis involve the scalp, making it the most frequently affected area of the body. The treatment of scalp psoriasis is particularly crucial because of its hard-to-treat nature and substantial adverse impacts on overall well-being. Along with the physical symptoms of discomfort and itching, psoriasis, especially when it affects the scalp, can cause severe psychological damage. Treating scalp psoriasis can be challenging due to its location and associated symptoms, such as scaling and pruritus, which is why various drugs have become widely used for refractory cases. Topical treatments like corticosteroids and vitamin D analogs manage scalp psoriasis by reducing inflammation and regulating skin cell growth. Tar-based shampoos, salicylic acid solutions, and moisturizers control scaling. Phototherapy with UVB light reduces inflammation. Severe cases may require systemic medications such as oral retinoids and immunosuppressants. While various therapies are accessible for scalp psoriasis, concerns arise due to their limited advantages and the absence of controlled studies assessing their effectiveness. Considering these challenges, there is a clear demand for innovative approaches to address this condition effectively. Recent advancements in topical therapies, phototherapy, systemic agents, and complementary therapies have shown promising results in managing scalp psoriasis. Also, the advent of biologics, specifically anti-IL-17 and anti-IL-23 drugs for scalp psoriasis, has seen significant improvements. The review highlights the lack of well-tolerated and effective treatments for scalp psoriasis and underscores the importance of further research in this area. The objective of this review is to clarify the different treatment options currently available or being investigated in clinical trials for managing scalp psoriasis.

Use of Total Parenteral Nutrition (TPN) as a Vehicle for Drug Delivery.

Total Parenteral Nutrition (TPN) is a method of providing nutrients directly into the bloodstream for individuals who are unable to meet their nutritional needs through the normal digestive process or gastrointestinal system. It provides macronutrients and micronutrients in a single container, reducing handling and contamination risks and making it more cost-effective. TPN has the potential to be used as a drug delivery system, with applications in combination therapies, personalized medicine, and integrating advanced technologies. It can enhance drug dosage precision and provide nutritional assistance, potentially reducing hospitalization and improving patient outcomes. However, implementing new applications requires thorough testing and regulatory approval. TPN could be particularly useful in pediatric and geriatric care and could also contribute to global health by combating malnutrition in areas with limited medical resources. Healthcare professionals prepare a sterile solution tailored to each patient's nutritional needs, and administration involves a central venous catheter. However, the simultaneous administration of medications with PN admixtures can result in pharmacological incompatibility, which can impact the stability of the oil-in-water system. The European Society for Clinical Nutrition and Metabolism and the American Society for Parenteral and Enteral Nutrition recommendations advise against including non-nutrient drugs in PN admixtures due to safety concerns. This review focuses on the utilization of Total Parenteral Nutrition (TPN) as a method for delivering drugs. It discusses the benefits and difficulties associated with its commercial application and offers suggestions for future research endeavors.

Scaffold hopping for designing of potent and selective CYP1B1 inhibitors to overcome docetaxel resistance: synthesis and evaluation.

Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive in-silico studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors. Initially, scaffold hopping analysis was performed against a well-reported potent and selective CYP1B1 inhibitor (i.e. compound 3n). A total of 200 scaffolds were identified along with their shape and field similarity scores. The top three scaffolds were further selected on the basis of these scores and their synthesis feasibility to design some potent and selective CYP1B1 inhibitors using the aforementioned in-silico techniques. Designed molecules were further synthesized to evaluate their CYP1B1 inhibitory activity and docetaxel resistance reversal potential against CYP1B1 overexpressed drug resistance MCF-7 cell line. In-vitro results indicated that compounds 2a, 2c and 2d manifested IC50 values for CYP1B1 ranging from 0.075, 0.092 to 0.088 µM with at least 10-fold selectivity. At low micromolar concentrations, compounds 1e, 1f, 2a and 2d exhibited promising cytotoxic effects in the docetaxel-resistant CYP1B1 overexpressed MCF-7 cell line. In particular, compound 2a is most effective in reversing the resistance with IC50 of 29.0 ± 3.6 µM. All of these discoveries could pave the way for the development of adjuvant therapy capable of overcoming CYP1B1-mediated resistance.Communicated by Ramaswamy H. Sarma.

Pre-clinical and cellular safety assessment of oral administered DHA rich microalgae oil from Schizochytrium sp. (Strain ATCC-20889): acute, sub-chronic and genotoxicity.

The lack of toxicity data for DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) leads to its exclusion from the Qualified Presumption of Safety list. Therefore, present study addresses toxicity evaluation of DHA-rich microalgae oil using ex-vivo (cytotoxicity assay) and in-vivo methods (acute (OECD 423 guidelines), sub-chronic (OECD 452 guidelines), and genotoxicity assay). The ex-vivo results showed >90% cell viability of Caco-2 cells after 48 h of treatment (200 µg/mL of DHA). Additionally, the in-vivo acute toxicity study found that microalgae oil was nontoxic and classified under category 5 molecule according to OECD 423 guidelines with a highest degree of safety at 2000 mg/kg b.w. The in-vivo sub-chronic study revealed no significant mortality and changes in feed intake, body weight, haematological, biochemical, neurological, and urine parameters after repeated 180-days administration of DHA-rich microalgae oil at 250 mg/kg, 500 mg/kg, and 1000 mg/kg. Moreover, histopathology evaluation, comet assay, chromosomal aberration, and micronuclei assay also confirmed the nontoxic behavior of DHA-rich oil. Thus, the results from the ex-vivo and in-vivo studies indicate that DHA-rich oil from Schizochytrium sp. (Strain ATCC-20889) is safe for use as a novel food, and can be included in infants, adults, pregnant women, and children formula.

Scaffold hopping based designing of selective ALDH1A1 inhibitors to overcome cyclophosphamide resistance: synthesis and biological evaluation.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is an isoenzyme that catalyzes the conversion of aldehydes to acids. However, the overexpression of ALDH1A1 in a variety of malignancies is the major cause of resistance to an anti-cancer drug, cyclophosphamide (CP). CP is a prodrug that is initially converted into 4-hydroxycyclophosphamide and its tautomer aldophosphamide, in the liver. These compounds permeate into the cell and are converted as active metabolites, i.e., phosphoramide mustard (PM), through spontaneous beta-elimination. On the other hand, the conversion of CP to PM is diverted at the level of aldophosphamide by converting it into inactive carboxyphosphamide using ALDH1A1, which ultimately leads to high drug inactivation and CP resistance. Hence, in combination with our earlier work on the target of resistance, i.e., ALDH1A1, we hereby report selective ALDH1A1 inhibitors. Herein, we selected a lead molecule from our previous virtual screening and implemented scaffold hopping analysis to identify a novel scaffold that can act as an ALDH1A1 inhibitor. This results in the identification of various novel scaffolds. Among these, on the basis of synthetic feasibility, the benzimidazole scaffold was selected for the design of novel ALDH1A1 inhibitors, followed by machine learning-assisted structure-based virtual screening. Finally, the five best compounds were selected and synthesized. All synthesized compounds were evaluated using in vitro enzymatic assay against ALDH1A1, ALDH2, and ALDH3A1. The results disclosed that three molecules A1, A2, and A3 showed significant selective ALDH1A1 inhibitory potential with an IC50 value of 0.32 µM, 0.55 µM, and 1.63 µM, respectively, and none of the compounds exhibits potency towards the other two ALDH isoforms i.e. ALDH2 and ALDH3A1. Besides, the potent compounds (A1, A2, and A3) have been tested for in vitro cell line assay in combination with mafosfamide (analogue of CP) on two cell lines i.e. A549 and MIA-PaCa-2. All three compounds show significant potency to reverse mafosfamide resistance by inhibiting ALDH1A1 against these cell lines.

Reference Range of Plasma Fatty Acids in North Indian Pregnant Population.

Reference values for Fatty Acids (FAs) are not well defined in the Indian population. Therefore, it is critical to establish FAs reference range for the healthy non-pregnant and pregnant Indian population. The present multi-centric, and cross-sectional study determines the 95% reference interval for FAs in an apparently pregnant Indian population and compare it to the healthy non-pregnant women. Physicians identified 164 reference individuals as healthy (56 non-pregnant and 108 pregnant) at various government and private hospitals of northern India. The 95th and 97.5th percentile reference limits were used to estimate the 95 percentile of the reference distribution. The reference ranges observed for Alpha-linolenic acid (0.29-0.42%; 0.36-0.58%), Docosahexaenoic-acid (3.38-4.23%; 3.8-4.55%), Eicosapentaenoic-acid (1.24-1.76%; 1.09-1.62%), Docosapentaenoic-acid-3 (0.61-0.69%; 0.65-0.76%), Linoleic-acid (18.44-20.75%; 19.51-21.88%), gamma-linolenic-acid (0.24-0.35%; 0.32-0.42%), Eicosatrienoic-acid (0.26-0.32%; 0.34-0.39%), Arachidonic-acid (9.29-11.02%; 10.02-11.56%), Docosatetraenoic-acid (0.62-0.89%; 0.79-1.09%), Docosapentaenoic-acid-6 (0.23-0.31%; 0.33-0.41%), Eicosatrienoic-acid (1.17-1.41%; 1.43-1.74%), Eicosenoic-acid (0.28-0.38%; 0.37-0.49%), Nervonic-acid (1.39-1.69%; 1.41-1.74%), Palmitoleic-acid (1.17-1.58%; 2-2.66%), Oleic-acid (19.8-22.26%; 19.68-22.94%), Myristic-acid (1.16-1.68%; 0.82-1.3%), Palmitic-acid (20.05-21.8%; 20.7-22.43%), Stearic-acid (11.34-12.56%; 10.29-11.02%), Arachidic-acid (0.17-0.2%; 0.18-0.23%), Lignoceric-acid (0.81-1.08%; 0.77-1.08%), trans-palmitoleic-acid (0.22-0.29%; 0.26-0.37%), trans-oleic-acid (0.55-0.72%; 0.68-0.84%), trans-linoleic-acid (0.38-0.54%; 0.42-0.59%) respectively for non-pregnant and pregnant women. Furthermore, total FAs were significantly (p ≤ 0:05) higher in women aged 31-45 years than in women aged 16-30 years. whereas, there was no significant change in total FAs profile based on omega-supplementation, diet category, preterm-birth history, and gestation period. Thus, the current study provides information about an individual who is deficient in FAs and the dose required to increase FA concentrations in the body.

Revolutionizing Pharmaceutical Industry: The Radical Impact of Artificial Intelligence and Machine Learning.

This article explores the significant impact of artificial intelligence (AI) and machine learning (ML) on the pharmaceutical industry, which has transformed the drug development process. AI and ML technologies provide powerful tools for analysis, decision-making, and prediction by simplifying complex procedures from drug design to formulation design. These techniques could potentially speed up the development of better medications and drug development processes, improving the lives of millions of people. However, the use of these techniques requires trained personnel and human surveillance for AI to function effectively, if not there is a possibility of errors like security breaches of personal data and bias can also occur. Thus, the present review article discusses the transformative power of AI and ML in the pharmaceutical industry and provides insights into the future of drug development and patient care.

Prenatal Supplementation of Docosahexaenoic Acid for the Management of Preterm Births: Clinical Information for Practice.

Unhealthy pregnancy and the resultant abnormalities in newborns exhibit a significant drawback. Each year, an estimated 15 million babies are born prematurely, accounting for the majority of deaths among children under the age of 5. India accounts for about a quarter of all preterm birth (PTB) incidences, with few therapeutic options available. However, research shows that consuming more marine foods (rich in omega-3 fatty acids (Ω-3), particularly Docosahexaenoic acid (DHA), helps to maintain a healthy pregnancy and can manage or prevent the onset of PTB and its accompanying difficulties. Present circumstances raise concerns about the use of DHA as a medication due to a lack of evidence on the dosage requirements, safety profile, molecular route, and commercially accessible strength for their therapeutic response. Several clinical experiments have been done over the last decade; however, the mixed outcomes have resulted in discrepancies. Most scientific organizations suggest a daily DHA consumption of 250-300 mg. However, this may differ from person to person. As a result, before prescribing a dosage, one should check the DHA concentrations in the individual's blood and then propose a dose that will benefit both the mother and the unborn. Thus, the review focuses on the favourable benefits of Ω-3, particularly DHA during pregnancy and postpartum, therapeutic dose recommendations, safety considerations, particularly during pregnancy, and the mechanistic pathway that might prevent or reduce the frequency of PTB accidents.

Raloxifene and bazedoxifene as selective ALDH1A1 inhibitors to ameliorate cyclophosphamide resistance: A drug repurposing approach.

Cyclophosphamide (CP) is one of the most widely used anticancer drugs for various malignancies. However, its long-term use leads to ALDH1A1-mediated inactivation and subsequent resistance which necessitates the development of potential ALDH1A1 inhibitors. Currently, ALDH1A1 inhibitors from different chemical classes have been reported, but these failed to reach the market due to safety and efficacy problems. Developing a new treatment from the ground requires a huge amount of time, effort, and money, therefore it is worthwhile to improve CP efficacy by proposing better adjuvants as ALDH1A1 inhibitors. Herein, the database constituting the FDA-approved drugs with well-established safety and toxicity profiles was screened through already reported machine learning models by our research group. This model is validated for discriminating the ALDH1A1 inhibitors and non-inhibitors. Virtual screening protocol (VS) from this model identified four FDA-approved drugs, raloxifene, bazedoxifene, avanafil, and betrixaban as selective ALDH1A1 inhibitors. The molecular docking, dynamics, and water swap analysis also suggested these drugs to be promising ALDH1A1 inhibitors which were further validated for their CP resistance reversal potential by in-vitro analysis. The in-vitro enzymatic assay results indicated that raloxifene and bazedoxifene selectively inhibited the ALDH1A1 enzyme with IC50 values of 2.35 and 4.41 µM respectively, whereas IC50 values of both the drugs against ALDH2 and ALDH3A1 was >100 µM. Additional in-vitro studies with well-reported ALDH1A1 overexpressing A549 and MIA paCa-2 cell lines suggested that mafosfamide sensitivity was further ameliorated by the combination of both raloxifene and bazedoxifene. Collectively, in-silico and in-vitro studies indicate raloxifene and bazedoxifene act as promising adjuvants with CP that may improve the quality of treatment for cancer patients with minimal toxicities.

Therapeutic and prophylactic effects of oral administration of probiotic Enterococcus faecium Smr18 in Salmonella enterica-infected mice.

Salmonella enterica serotype Typhi causes chronic enteric fever known as typhoid. Prolonged treatment regimen used for the treatment of typhoid and indiscriminate use of antibiotics has led to the emergence of resistant strains of S. enterica that has further increased the severity of the disease. Therefore, alternative therapeutic agents are urgently required. In this study, probiotic and enterocin-producing bacteria Enterococcus faecium Smr18 was compared for both its prophylactic and therapeutic efficacy in S. enterica infection mouse model. E. faecium Smr18 possessed high tolerance to bile salts and simulated gastric juice, as treatment for 3 and 2 h resulted in 0.5 and 0.23 log10 reduction in the colony forming units, respectively. It exhibited 70% auto aggregation after 24 h of incubation and formed strong biofilms at both pH 5 and 7. Oral administration of E. faecium in BALB/c mice infected with S. enterica significantly (p < 0.05) reduced the mortality of the infected mice and prevented the weight loss in mice. Administration of E. faecium prior to infection inhibited the translocation of S. enterica to liver and spleen, whereas, its administration post-infection completely cleared the pathogen from the organs within 8 days. Further, in both pre- and post-E. faecium-treated infected groups, sera levels of liver enzymes were restored back to normal; whereas the levels of creatinine, urea and antioxidant enzymes were significantly (p < 0.05) reduced compared to the untreated-infected group. E. faecium Smr18 administration significantly increased the sera levels of nitrate by 1.63-fold and 3.22-fold in pre- and post-administration group, respectively. Sera levels of interferon-γ was highest (tenfold) in the untreated-infected group, whereas the levels of interleukin-10 was highest in the post-infection E. faecium-treated group thereby indicating the resolution of infection in the probiotic-treated group, plausibly due to the increased production of reactive nitrogen intermediates.

Proteins in Complement, Immune, and Clotting Cascades and their Role in Preterm Births.

Preterm birth (PTB) (< 37 completed weeks gestation) is a pathological outcome of pregnancy and its associated complications are the leading global cause of death in children younger than 5 years of age. Babies born prematurely have an elevated risk for short- and long-term adverse effects of medical and neurodevelopmental sequelae. Substantial evidence suggests that multiple sets of symptoms are allied with PTB etiology, and the exact mechanism cannot be recognized. Notably, various proteins, especially (i) complement cascade; (ii) immune system; and (iii) clotting cascade, have become attractive research targets that are associated with PTB. Further, a small imbalance of these proteins in maternal or foetal circulation could serve as a marker/precursor in a series of events that lead to PTBs. Thus, the present review lightens the basic description of the circulating proteins, their role in PTB, and current concepts for future development. Further, deepening the research on these proteins will lead to a better understanding of PTB etiology and alleviate scientists' confidence in the early identification of PTB mechanisms and biological markers.

Genotoxic and mutagenic potential of 7-methylxanthine: an investigational drug molecule for the treatment of myopia.

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX.

Preparation and Characterisation of Liposomes of Bergenia Ciliata Extract and Evaluation of their Hepatoprotective Activity.

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-ß1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678-1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-ß1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

Novel Hyaluronic Acid ethosomes based gel formulation for topical use with reduced toxicity, better skin permeation, deposition, and improved pharmacodynamics.

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it's commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of -6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.

Nascent Nanoformulations as an Insight into the Limitations of the Conventional Systemic Antifungal Therapies.

More than 150 million people have significant fungal diseases that greatly impact health care and economic expenditures. The expansion of systemic fungal infections and invasive mycoses is being driven by an increase in the number of immunocompromised patients and the recent COVID-19 patients, especially severely ill. There have been numerous cases of fungal infections linked to COVID-19, with pulmonary aspergillosis dominating at first but with the subsequent appearance of mucormycosis, candidiasis, and endemic mycoses. Candida spp. is the most frequent pathogen, with approximately 1 billion infections yearly, among other species causing the most prevalent invasive fungal infections. The importance of recognizing the epidemiological shifts of invasive fungal infections in patient care cannot be overstated. Despite the enormous antifungal therapies available, these infections are difficult to diagnose and cause high morbidity and mortality rates. Treatment choices for systemic fungal infections are severely limited due to the limitations of conventional therapy effectiveness and drug toxicities. So the researchers are still looking for novel therapeutic options, such as carrier-based approaches that are convenient and cost-effective with high and long-lasting fungal infection cure rates with reduced toxicities. The focus of this study is on summarizing the nanotechnology, immunotherapy methods and the drugs under clinical trials that have been employed in treatment as carrier-based antifungal formulations. Most of these have been reported to be promising strategies with broad-spectrum antifungal action and the potential to overcome antibiotic resistance mechanisms. We speculate that this review summarized the current knowledge to its best that will help the future developments of new antifungal therapies.

Machine Learning Enabled Structure-Based Drug Repurposing Approach to Identify Potential CYP1B1 Inhibitors.

Drug-metabolizing enzyme (DME)-mediated pharmacokinetic resistance of some clinically approved anticancer agents is one of the main reasons for cancer treatment failure. In particular, some commonly used anticancer medicines, including docetaxel, tamoxifen, imatinib, cisplatin, and paclitaxel, are inactivated by CYP1B1. Currently, no approved drugs are available to treat this CYP1B1-mediated inactivation, making the pharmaceutical industries strive to discover new anticancer agents. Because of the extreme complexity and high risk in drug discovery and development, it is worthwhile to come up with a drug repurposing strategy that may solve the resistance problem of existing chemotherapeutics. Therefore, in the current study, a drug repurposing strategy was implemented to find the possible CYP1B1 inhibitors using machine learning (ML) and structure-based virtual screening (SB-VS) approaches. Initially, three different ML models were developed such as support vector machines (SVMs), random forest (RF), and artificial neural network (ANN); subsequently, the best-selected ML model was employed for virtual screening of the selleckchem database to identify potential CYP1B1 inhibitors. The inhibition potency of the obtained hits was judged by analyzing the crucial active site amino acid interactions against CYP1B1. After a thorough assessment of docking scores, binding affinities, as well as binding modes, four compounds were selected and further subjected to in vitro analysis. From the in vitro analysis, it was observed that chlorprothixene, nadifloxacin, and ticagrelor showed promising inhibitory activity toward CYP1B1 in the IC50 range of 0.07-3.00 µM. These new chemical scaffolds can be explored as adjuvant therapies to address CYP1B1-mediated drug-resistance problems.

Myopia, its prevalence, current therapeutic strategy and recent developments: A Review.

Myopia is a widespread and complex refractive error in which a person's ability to see distant objects clearly is impaired. Its prevalence rate is increasing worldwide, and as per WHO, it is projected to increase from 22% in 2000 to 52% by 2050. It is more prevalent in developed, industrial areas and affects individuals of all ages. There are a number of treatments available for the control of myopia, such as glasses, contact lenses, laser surgery, and pharmaceuticals agents. However, these treatments are less beneficial and have significant side effects. A novel molecule, 7-methylxanthine (7-MX), has been found to be a highly beneficial alternate in the treatment of myopia and excessive eye elongation. Many preclinical and clinical studies showed that 7-MX is effective for the treatment of myopia and is presently under phase II of clinical investigation. We have also investigated preclinical toxicity studies such as acute, sub-acute, sub-chronic, and chronic on rats. In these studies, 7-MX was found to be non-toxic as compared to other reported anti-myopic agents. Moreover, as an ideal drug, 7-MX is observed to have no or low toxicity, brain permeability, non-allergic, higher oral administration efficacy, and low treatment costs and thus qualifies for the long-term treatment of myopia. This review article on 7-MX as an alternative to myopia treatment will highlight recent findings from well-designed preclinical and clinical trials and propose a potential future therapy.

Micro RNAs as Emerging Therapeutic Targets in Liver Diseases.

MicroRNAs (MiRNAs) are endogenous non-coding small RNA molecules that regulate gene expression in plants, animals and some viruses. Both normal and pathological liver processes are regulated by miRNAs. Recent research indicated that miRNAs have been implicated in liver diseases caused by viral hepatitis (Hepatitis B and Hepatitis C), metabolic problems, alcohol and drug abuse. Because altered miRNA expression is linked to liver metabolic dysregulation, liver damage, liver fibrosis, and tumour growth, miRNAs are promising therapeutic targets for the detection and treatment of liver diseases. In this review, we summarise the current knowledge about the role of microRNAs in acute and chronic liver diseases, including hepatocellular carcinoma. We cover the miRNA-based therapy for liver disorders as well as the use of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases. The investigation of miRNAs in liver diseases will provide a better understanding of the pathogeneses, identification of biomarkers and therapeutic targets for liver diseases in the future.

Spray-Dried Microspheres of Carboplatin: Technology to Develop Longer-Acting Injectable with Improved Physio-Chemical Stability, Toxicity, and Therapeutics.

The present study aims to develop carboplatin injectable microspheres using spray-drying technology. The optimized powdered microspheres (MS-19-ST2) were morphologically spherical, with a 1.795 µm particle size and good micromeritic properties. Under normal temperature conditions, the MS-19-ST2 formulation exhibited a sustained release behaviour following first-order drug release kinetics with no compatibility issues with aluminium syringes. Furthermore, MS-19-ST2 formulation outperformed its commercial counterpart in terms of in vivo pharmaco-kinetics and -dynamics (MRT-13.9 ± 0.9 h, T1/2-8.2 ± 0.3 h, tumour inhibition-74.5%). Additionally, the MS-19-ST2 formulation was much safer to use than its commercial counterpart, as observed from the results of ex vivo (haemolytic, MTT, and cell apoptosis assays) and in vivo (14-day acute and 28-day sub-acute) toxicity studies. The above results confirm the MS-19-ST2 formulation as a good candidate to commercialize carboplatin in a powdered microsphere form (stable for 24 h after reconstitution) with improved pharmacokinetics, therapeutic, and toxicity profile.