From propolis to nanopropolis: An exemplary journey and a paradigm shift of a resinous substance produced by bees.

Propolis, a natural resinous mixture produced by honey bees is poised with diverse biological activities. Owing to the presence of flavonoids, phenolic acids, terpenes, and sesquiterpenes, propolis has garnered versatile applications in pharmaceutical industry. The biopharmaceutical issues associated with propolis often beset its use as being too hydrophobic in nature; it is not absorbed in the body well. To combat the problem, various nanotechnological approaches for the development of novel drug delivery systems are generally applied to improve its bioavailability. This paradigm shift and transition of conventional propolis to nanopropolis are evident from the literature wherein a multitude of studies are available on nanopropolis with improved bioavailability profile. These approaches include preparation of gold nanoparticles, silver nanoparticles, magnetic nanoparticles, liposomes, liquid crystalline formulations, solid lipid nanoparticles, mesoporous silica nanoparticles, etc. Nanopropolis has further been explored to assess the potential benefits of propolis for the development of futuristic useful products such as sunscreens, creams, mouthwashes, toothpastes, and nutritional supplements with improved solubility, bioavailability, and penetration profiles. However, more high-quality clinical studies assessing the effects of propolis either alone or in combination with synthetic drugs as well as natural products are warranted and its safety needs to be firmly established.

Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations.

This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1-C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand-protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 µM) in correlation with the in silico results (binding energies = -8.55 to -8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π-π, π-cation, π-sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.

Development and Optimization of Methylcellulose-Based Nanoemulgel Loaded with Nigella sativa Oil for Oral Health Management: Quadratic Model Approach.

The present study aimed to develop a local dental nanoemulgel formulation of Nigella sativa oil (NSO) for the treatment of periodontal diseases. NSO purchased from a local market was characterized using a GC-MS technique. A nanoemulsion containing NSO was prepared and incorporated into a methylcellulose gel base to develop the nanoemulgel formulation. The developed formulation was optimized using a Box-Behnken statistical design (quadratic model) with 17 runs. The effects of independent factors, such as water, oil, and polymer concentrations, were studied on two dependent responses, pH and viscosity. The optimized formulation was further evaluated for droplet size, drug release, stability, and antimicrobial efficacy. The developed formulation had a pH of 7.37, viscosity of 2343 cp, and droplet size of 342 ± 36.6 nm. Sustained release of the drug from the gel for up to 8 h was observed, which followed Higuchi release kinetics with non-Fickian diffusion. The developed nanoemulgel formulation showed improved antimicrobial activity compared to the plain NSO. Given the increasing emergence of periodontal diseases and antimicrobial resistance, an effective formulation based on a natural antibacterial agent is warranted as a dental therapeutic agent.

Study of influence of Catha edulis (Khat) chewing on oral pharmacokinetics of irbesartan in rats using a newly developed HPLC-UV method.

Khat consumers might use a number of drugs for underlying conditions; however the potential drug-herb interaction between khat and other drugs including Irbesartan (IRB) is unknown. The present study was conducted to evaluate the effects of khat chewing on pharmacokinetic profile of IRB, a commonly available antihypertensive agent. The pharmacokinetic profile of orally administered IRB (15.5 mg/kg) with and without pre-administration of khat (12.4 mg/kg) were determined in Sprague-Dawley rats. IRB was estimated in rat plasma samples using a newly developed HPLC method. The chromatographic separation of the drug and internal standard (IS) was performed on a C-18 column (Raptor C-18, 100 mm × 4.6 mm id.; 5 µm) using a mobile phase consisting of 10 mM ammonium acetate buffer (pH 4.0) and acetonitrile in a ratio 60:40 v/v. Acceptable linearity for IRB was recorded at 1 - 12 µg/mL concentration range (R2 > 0.99). Intra-day and inter-day precision (%RSD = 0.44% - 3.27% and 0.39-1.98% respectively) and accuracy (% recovery = 98.3 - 104.3%) in rat plasma was within the acceptable limit according to USFDA guidelines. The AUC0-t was found to be significantly increased in IRB-khat co-administered rats as compared to rats receiving IRB only; whereas, the Tmax (0.5 h) value remained unchanged. Results of this study revealed that the IRB level considerably increased in rat plasma upon co-administration of khat. This might be due to the inhibition of CYP2D9 by khat which is the principal cytochrome P450 isoform responsible for IRB metabolism.

Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Genotoxicity of yellow shammah (smokeless tobacco) in murine bone marrow cells in vivo.

Shammah is a traditional form of smokeless tobacco (ST) that is manufactured and used locally by people of Middle East with highest usage in Saudi Arabia, Yemen and Sudan. In Saudi Arabia, shammah comes in three variants: white, brown and yellow. In the present study, we investigated the genotoxicity of yellow shammah (YS) on bone marrow (BM) cells in vivo using mice. Bone marrow (BM) chromosomal aberration (CA) and micronucleus (MN) assay were performed and hepatic markers of oxidative stress were determined. Swiss albino mice were divided into five groups (n = 6) including negative control (NC) and positive control (PC) groups. The three treated groups included YS-100, 200 and 300 mg/kg, doses freshly prepared in 0.5% carboxymethyl cellulose (CMC) and administered orally once a day for 2 weeks. PC animals were administered cyclophosphamide (CP) at a dose of 40 mg/kg body weight, 24 h before termination. Two weeks continuous treatment of YS induced a dose dependent and significant increase in aberrant metaphases (AM), CA per cell and depression in mitotic activity. In micronucleus assay, YS treatment increased the percentage of micronucleated polychromatic erythrocytes (MNPCE) frequency and showed statistically significant reduction in polychromatic erythrocyte/normochromatic erythrocyte ratio at all doses, as compared to NC. YS also markedly inhibited the activities of superoxide dismutase, reduced glutathione and increased malondialdehyde content. CP was used as clastogen (positive control) and yielded the expected positive results. Therefore, it may be concluded that YS has genotoxic and cytotoxic effects for BM cells of mice in vivo.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

In vivo assessment of genotoxic potential of brown shammah (smokeless tobacco) in bone marrow cells of mice.

This study was aimed to assess the genotoxicity of brown shammah (BS), a local form of smokeless tobacco, popular in Middle East countries including Yemen, Saudi Arabia and Sudan. The genotoxicity was explored using in vivo chromosomal aberration (CA), micronucleus (MN) and sperm abnormality (SA) assays. In addition, oxidative stress was also determined using various hepatic markers. Swiss albino mice were selected for the study, which were divided in to 5 groups of six animals each. They include, negative control (NC, received only vehicle) as well as positive control group (PC, received vehicle for 2 weeks followed by administration of cyclophosphamide, CP). Depending upon their dose, three BS treated animal groups were BS-100, 300 and 900 mg/kg. Doses of BS were obtained by suspending BS in 0.5% CMC (carboxy methyl cellulose) and orally administered once a day for 2 weeks. Significant augmentation of the average percentage of aberrant metaphase (AM), CA per cells and suppressed mitotic activity was observed on post administration of BS. In addition, BS increased the occurrence of MNPCEs (micronucleated polychromatic erythrocytes) formation, induced cytotoxicity and increased percentage of abnormal sperms as compared to NC. Moreover, BS also induced oxidative stress as the activities of hepatic superoxide dismutase (SOD) and glutathione (GSH) were reduced and malondialdehyde (MDA) content were increased by BS. Cyclophosphamide was utilized as clastogen, showed anticipated positive results and confirmed the sensitivity of test system. Therefore, it may be deduced from the study that the BS possesses genotoxic effects on mice bone marrow and germ cells in vivo.

Analysis of amphetamine and methamphetamine contents in seized tablets from Jazan, Saudi Arabia by liquid chromatography-mass spectroscopy (LC-MS/MS) and chemometric techniques.

A number of illegal amphetamine tablets were seized from three different cities of Jazan province of southern Saudi Arabia and were analyzed for amphetamine and methamphetamine contents using LC-MS/MS technique. Analyses were performed using a previously reported method taking 0.1 M ammonium formate buffer (85%) and 15% acetonitrile with 0.1% formic acid as mobile phase with a total runtime of 12 min. This method was successfully applied for the routine analysis of amphetamine and methamphetamine in the seized tablets using amphetamine-D5 and methamphetamine-D5 as internal standards. Hierarchical cluster analysis was performed to establish the similarity between samples. The retention times (RT) for internal standard, amphetamine and methamphetamine were observed to be within 6.0-7.1 min. Ten tablet samples from each city were subjected to analysis and the amount of amphetamine in all the samples were found to be in the range of 9.07-14.77 mg, whereas, the amount of methamphetamine ranged from 0.12 to 0.24 mg in each tablet. Hierarchical cluster analysis showed presence of five clusters of samples indicating different characteristics and possible sources of amphetamine tablets. The largest cluster consisted of 15 samples which are expected to be of the same origin. Both amphetamine and methamphetamine are considered to be illegal products and their illegal trade and use is banned in many countries including Saudi Arabia. Therefore, there is an urgent need of strict regulations worldwide to check the illicit trafficking of these psychoactive substances and should be considered on priority.

Risk-based exposure assessment for multiple toxic elements encountered by children in school playgrounds and parks in the southwest region of Saudi Arabia.

Children are in direct contact with surface soil and may inadvertently ingest and inhale toxic contaminants while playing; hence, special attention should be given to playgrounds regarding toxic contaminants. The concentrations of ten toxic metals were determined in soil samples collected from school playgrounds and children's parks from the southwest region of Saudi Arabia. The soils were moderately alkaline (pH 7.6-8.8), the texture was dominated by sand particles (54-88%), and the organic matter was in the range of 2.06 to 4.82%. Analytical solutions were prepared by microwave-digestion using a HNO3/H2O2 mixture, and the concentrations of toxic elements were measured by inductively coupled plasma mass spectrometry (ICP-MS). Metal concentrations were recorded in the range of 0.014-0.087, 1.14-3.54, 0.85-23.29, 0.77-36.32, 312.6-2065.7, 285.3-822.6, 75.4-240.8, 0.00-53.12, 0.52-6.80, and 1.25-92.12 mg/kg dry soil for Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, and Zn, respectively. The levels of heavy metals in the studied playgrounds were below the permissible limits, indicating insignificant influence of anthropogenic activities and can be considered as unpolluted soil. Values of the enrichment coefficient (EC) and contamination factor (CF) were found to be less than one, suggesting that the source of these elements is mainly the local soil, with the exception of Ni and Zn in certain playgrounds (CF > 1), which indicates a possible contamination from external sources. The non-carcinogenic hazard index calculated for all of the metals was below one, indicating that the exposure to heavy metal through playground soil is unlikely to produce any adverse health effect in children playing in the playgrounds.

Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges.

The programmed death-1 receptor (PD-1) acts as a T-cell brake, and its interaction with ligand-1 (PD-L-1) interferes with signal transduction of the T-cell receptor. This leads to suppression of T-cell survival, proliferation, and activity in the tumor microenvironment resulting in compromised anticancer immunity. PD-1/PD-L-1 interaction blockade shown remarkable clinical success in various cancer immunotherapies. To date, most PD-1/PD-L-1 blockers approved for clinical use are monoclonal antibodies (mAbs); however, their therapeutic use are limited owing to poor clinical responses in a proportion of patients. mAbs also displayed low tumor penetration, steep production costs, and incidences of immune-related side effects. This strongly indicates the importance of developing novel inhibitors as cancer immunotherapeutic agents. Recently, advancements in the small molecule-based inhibitors (SMIs) that directly block the PD-1/PD-L-1 axis gained attention from the scientific community involved in cancer research. SMIs demonstrated certain advantages over mAbs, including longer half-lives, low cost, greater cell penetration, and possibility of oral administration. Currently, several SMIs are in development pipeline as potential therapeutics for cancer immunotherapy. To develop new SMIs, a wide range of structural scaffolds have been explored with excellent outcomes; biphenyl-based scaffolds are most studied. In this review, we analyzed the development of mAbs and SMIs targeting PD-1/PD-L-1 axis for cancer treatment. Altogether, the present review delves into the problems related to mAbs use and a detailed discussion on the development and current status of SMIs. This article may provide a comprehensive guide to medicinal chemists regarding the potential structural scaffolds required for PD-1/PD-L-1 interaction inhibition.

Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ.

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.

Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.

Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.

BACKGROUND: Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. METHODS: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included "Friedreich's ataxia," "treatment," "drug candidates," and "mechanisms of action." RESULTS: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. CONCLUSION: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Pharmaceutical applications of therapeutic deep eutectic systems (THEDES) in maximising drug delivery.

The issue of poor solubility of active pharmaceutical ingredients (APIs) has been a salient area of investigation and novel drug delivery systems are being developed to improve the solubility of drugs, enhance their permeability and thereby their efficacy. Several techniques for solubilization enhancement of poorly soluble drugs are often employed at various stages of pharmaceutical drug product development. One such delivery system is the therapeutic deep eutectic system (THEDES), which showed great potential in the enhancement of solubility and permeability of drugs and ultimately augmenting their bioavailability. THEDES are made by mixing drugs with deep eutectic solvents (DESs) in a definite molar ratio by the hit and trial method. The DESs are a new class of green solvents which are non-toxic, cheap, easy to prepare, biodegradable and have multiple applications in the pharmaceutical industry. The terminologies such as ionic liquids (ILs), DES, THEDES, and therapeutic liquid eutectic systems (THELES) have been very much in use recently, and it is important to highlight the pharmaceutical applications of these unexplored reservoirs in drug solubilization enhancement, drug delivery routes, and in the management of various diseases. This review is aimed at discussing the components, formulation strategies, and routes of administration of THEDES that are used in developing the formulation. Also, the major pharmaceutical applications of THEDES in the treatment of various metabolic and non-metabolic diseases are reviewed.

Multivariate Statistical 2D QSAR Analysis of Indenoisoquinoline-based Topoisomerase- I Inhibitors as Anti-lung Cancer Agents.

BACKGROUND: Indenoisoquinoline-based compounds have shown promise as topoisomerase-I inhibitors, presenting an attractive avenue for rational anticancer drug design. However, a detailed QSAR study on these derivatives has not been performed till date. OBJECTIVE: This study aimed to identify crucial molecular features and structural requirements for potent topoisomerase- 1 inhibition. METHODS: A comprehensive two-dimensional (2D) QSAR analysis was performed on a series of 49 indenoisoquinoline derivatives using TSAR3.3 software. A robust QSAR model based on a training set of 33 compounds was developed achieving favorable statistical values: r2 = 0.790, r2CV = 0.722, f = 36.461, and s = 0.461. Validation was conducted using a test set of nine compounds, confirming the predictive capability of the model (r2 = 0.624). Additionally, artificial neural network (ANN) analysis was employed to further validate the significance of the derived descriptors. RESULTS: The optimized QSAR model revealed the importance of specific descriptors, including molecular volume, Verloop B2, and Weiner topological index, providing essential insights into effective topoisomerase-1 inhibition. We also obtained a robust partial least-square (PLS) analysis model with high predictive ability (r2 = 0.788, r2CV = 0.743). The ANN results further reinforced the significance of the derived descriptors, with strong r2 values for both the training set (r2 = 0.798) and the test set (r2 = 0.669). CONCLUSION: The present 2D QSAR analysis offered valuable molecular insights into indenoisoquinoline-based topoisomerase- I inhibitors, supporting their potential as anti-lung cancer agents. These findings contribute to the rational design of more effective derivatives, advancing the development of targeted therapies for lung cancer treatment.

Amelioration of the therapeutic potential of gefitinib against breast cancer using nanostructured lipid carriers.

Aim: This study aimed to improve the delivery and therapeutic potential of gefitinib (GTB) against breast cancer by preparing GTB-loaded, nanostructured lipid carriers (GTB-NLCs). Materials & methods: Box-Behnken design was used for optimization and GTB was loaded into NLCs using ultrasonication. The GTB-NLCs were characterized using in vitro, ex vivo and in vivo studies. The anticancer efficacy of GTB-NLCs was evaluated using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity and flow cytometry on MCF-7 breast cancer cell lines. Results: Optimized GTB-NLCs were successfully characterized and demonstrated improved internalization and enhanced cytotoxicity compared with plain GTB. Gut permeation studies showed enhanced intestinal permeability, and pharmacokinetic analysis revealed 2.6-fold improvement in GTB oral bioavailability. Conclusion: GTB-NLCs effectively enhanced the therapeutic potential of GTB against breast cancer.

Gefitinib is an important drug approved for the treatment of cancer. However, there are issues with gefitinib, including its low water solubility and toxicity. Being poorly water soluble, the absorption of gefitinib in blood is low and therefore high doses are required to achieve the therapeutic level. Also, gefitinib is nonselective for cancer as well as noncancer cells, leading to toxicity on other organs. This study aimed to incorporate gefitinib into a lipid-based carrier, which improved its properties such as solubility, stability and bioavailability. The prepared formulation was tested for its drug release, stability and efficacy on breast cancer cell lines as well as toxicity using various methods. It was observed that the prepared formulation not only improved bioavailability but also improved the targeting as more gefitinib entered the cancer cells when present in the formulation, decreasing the toxicity of gefitinib on other organs. In conclusion, the prepared formulation can be regarded as an effective approach to improving the therapeutic potential of gefitinib.

Bromelain: a review of its mechanisms, pharmacological effects and potential applications.

The utilization of plant-derived supplements for disease prevention and treatment has long been recognized because of their remarkable potential. Ananas comosus, commonly known as pineapple, produces a group of enzymes called bromelain, which contains sulfhydryl moieties. Recent studies have shown that bromelain exhibits a wide range of activities, including anti-inflammatory, anti-diabetic, anti-cancer, and anti-rheumatic properties. These properties make bromelain a promising drug candidate for the treatment of various diseases. The anti-inflammatory activity of bromelain has been shown to be useful in treating inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and asthma, whereas the anti-cancer activity of bromelain is via induction of apoptosis, inhibition of angiogenesis, and enhancement of the body's immune response. The anti-diabetic property of bromelain is owing to the improvement in glucose metabolism and reduction in insulin resistance. The therapeutic potential of bromelain has been investigated in numerous preclinical and clinical studies and a number of patents have been granted to date. Various formulations and delivery systems are being developed in order to improve the efficacy and safety of this molecule, including the microencapsulated form to treat oral inflammatory conditions and liposomal formulations to treat cancer. The development of novel drug delivery systems and formulations has further ameliorated the therapeutic potential of bromelain by improving its bioavailability and stability, while reducing the side effects. This review intends to discuss various properties and therapeutic applications of bromelain, along with its possible mechanism of action in treating various diseases. Recent patents and clinical trials concerning bromelain have also been covered.

Gefitinib: An Updated Review of its Role in the Cancer Management, its Nanotechnological Interventions, Recent Patents and Clinical Trials.

BACKGROUND: Gefitinib, a tyrosine kinase inhibitor, is effectively used in the targeted treatment of malignant conditions. It suppresses the signal transduction cascades leading to cell proliferation in the tumors and is now currently approved in several countries globally as secondline and third-line treatment for non-small cell lung cancer (NSCLC). OBJECTIVE: This review is aimed to summarize the journey of gefitinib as an established anticancer drug for the management of various cancers. Moreover, this review will focus on the mechanism of action, established anticancer activities, combination therapy, nanoformulations, as well as recent clinical trials and patents on gefitinib. METHODS: The data for this review was collected from scientific databases such as PubMed, Science Direct, Google Scholar, etc. Recent patents on gefitinib granted in the last two years were collected from databases Patentscope, USPTO, Espacenet, InPASS and Google Patents. Data for the recent clinical trials were obtained from the U.S. National Library of Medicine database. RESULTS: Recent pre-clinical and clinical studies during the period 2015-2021 demonstrating the efficacy of gefitinib were selected and summarized. Total 31 patents were granted in the year 2020-2021 concerning gefitinib. The efficacy of gefitinib against lung cancer, as well as other cancer types, including breast, prostate, colon, cervix etc., was reviewed. CONCLUSION: Gefitinib showed significant advantages in being more effective, safer and more stable, and the associated biopharmaceutical problems are addressed by the application of nanotechnology. The combination therapy using gefitinib and various anticancer molecules of natural and synthetic origin has shown an improved anticancer profile.

Heavy Metal Contamination in Leafy Vegetables Grown in Jazan Region of Saudi Arabia: Assessment of Possible Human Health Hazards.

The food chain, through vegetable consumption, is considered to be an important route of heavy metal exposure. Therefore, in this study, heavy metal concentrations in leafy vegetables grown in the Jazan region of Saudi Arabia were assessed using an ICP-MS. Lettuce, radish, mint, parsley and jarjir (Arugula) were selected for study and subjected to digestion using HCl. The results indicated that the Fe level was highest in all vegetables, while jarjir was the most contaminated vegetable. However, no tested metal exceeded the maximum permissible limits set by the FAO/WHO and European Committee. The possible health hazards associated with the exposure to metal contaminants via vegetable consumption were evaluated by estimating target hazard quotient (THQ) values, and the results revealed that the vegetables grown in close proximity of Jazan city were the most contaminated and those in Darb the least. However, the daily intakes of all the tested metals were well below the corresponding oral reference doses (RfDs), and the THQ values were less than unity, suggesting that the vegetables grown in the studied region were safe and the heavy metal exposure via vegetable consumption was unlikely to cause adverse effects to the local inhabitants of the region.

A review of nanomaterials from synthetic and natural molecules for prospective breast cancer nanotherapy.

Breast cancer being one of the most frequent cancers in women accounts for almost a quarter of all cancer cases. Early and late-stage breast cancer outcomes have improved dramatically, with considerable gains in overall survival rate and disease-free state. However, the current therapy of breast cancer suffers from drug resistance leading to relapse and recurrence of the disease. Also, the currently used synthetic and natural agents have bioavailability issues which limit their use. Recently, nanocarriers-assisted delivery of synthetic and natural anticancer drugs has been introduced to the breast cancer therapy which alienates the limitations associated with the current therapy to a great extent. Significant progress has lately been made in the realm of nanotechnology, which proved to be vital in the fight against drug resistance. Nanotechnology has been successfully applied in the effective and improved therapy of different forms of breast cancer including invasive, non-invasive as well as triple negative breast cancer (TNBC), etc. This review presents a comprehensive overview of various nanoformulations prepared for the improved delivery of synthetic and natural anticancer drugs alone or in combination showing better efficacy and pharmacokinetics. In addition to this, various ongoing and completed clinical studies and patents granted on nanotechnology-based breast cancer drug delivery are also reviewed.