Understanding the feasibility of chemotherapeutic and immunotherapeutic targets against non-small cell lung cancers: an update of resistant responses and recent combinatorial therapies.

Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to prostate, breast, and other cancers. Statistics associate ~25% of 2021 cancer-related deaths with LC, more than 80% of which are explicitly caused by tobacco smoking. Prevailing as small and non-small cell pathologies, with respective occurring frequency of nearly 15% and 80-85%, non-small cell LCs (NSCLCs) are prominently distinguished into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes. Since the first use of epidermal growth factor receptor (EGFR) inhibitor gefitinib for NSCLC treatment in 2002, immense progress has been made for targeted therapies with the next generation of drugs spanning across the chronological generations of small molecule inhibitors. The last two years have overseen the clinical approval of more than 10 therapeutic agents as first-line NSCLC medications. However, uncertain mutational aberrations as well as systemic resistant responses, and abysmal overall survival curtail the combating efficacies. Of late, immune checkpoint inhibitors (ICIs) against various molecules including programmed cell death-1 (PD-1) and its ligand (PD-L1) have been demonstrated as reliable LC treatment targets. Keeping these aspects in mind, this review article discusses the success of NSCLC chemo and immunotherapies with their characteristic effectiveness and future perspectives.

Intracellular ROS production and apoptotic effect of quinoline and isoquinoline alkaloids on the growth of Trypanosoma evansi.

Trypanosoma evansi, a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC50/24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC50 to IC50. Among the selected alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in reactive oxygen species (ROS) production. Therefore, increased apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi-infected mice model.

In vitro and in vivo evaluation of efficacy of berberine chloride: Phyto-alternative approach against Trypanosoma evansi infection.

Current chemotherapy against the Surra organism, Trypanosoma evansi has several limitations in terms of efficacy, toxicity, availability and emerging resistance. These reasons make the search of new chemo-preventive and chemo-therapeutic agent with high potency and low toxicity. Alkaloid phyto-molecules, berberine has shown promising anti-kinetoplastid activity against T. cruzi, T. congolense, T. brucei, Leishmania donovani and L. tropica. However, till date, there is no investigation of therapeutic efficacy of berberine chloride (BC) against T. evansi. The IC50 value of BC for growth inhibition of T. evansi at 24 h of culture was calculated as 12.15 µM. The specific selectivity index (SSI) of BC was calculated as 19.01 and 10.43 against Vero cell line and Equine PBMC's, respectively. Thirteen drug target genes affecting various metabolic pathways were studied to investigate the mode of trypanocidal action of BC. In transcript analysis, the mRNA expression of arginine kinase 1 remained refractory to exposure with BC, which provides metabolic plasticity in adverse environmental conditions. In contrary, rest all the drug target gene were down-regulated, which indicates that drug severely affect DNA replication, cell proliferation, energy homeostasis, redox homeostasis and calcium homeostasis of T. evansi, leading to the death of parasite in low concentrations. It is the first attempt to investigate in vitro anti-trypanosomal activity of BC against T. evansi. These data imply that phytochemicals as alternative strategies can be explored in the future as an alternative treatment for Surra in animal.

Polyhydroxybutyrate (PHB) in nanoparticulate form improves physical and biological performance of scaffolds.

Polyhydroxyalkanoates (PHAs) are natural polyesters produced by microorganisms as a source of intracellular energy reserves. Due to their desirable material characteristics, these polymers have been thoroughly investigated for tissue engineering and drug delivery applications. A tissue engineering scaffold serves as a substitute of the native extracellular matrix (ECM) and plays a crucial role in tissue regeneration by providing temporary support for cells during natural ECM formation. In this study, porous, biodegradable scaffolds were prepared using native polyhydroxybutyrate (PHB) and PHB in nanoparticulate form using salt leaching method, to investigate the differences in the physicochemical properties such as crystallinity, hydrophobicity, surface morphology, roughness, and surface area and biological properties of the prepared scaffolds. As per the BET analysis, PHB nanoparticles-based (PHBN) scaffolds presented a significant difference in the surface area as compare to PHB scaffolds. PHBN scaffolds showed decreased crystallinity and improved mechanical strength as compared to PHB scaffolds. Thermogravimetry analysis shows delayed degradation of PHBN scaffolds. An examination of Vero cell lines' cell viability and adhesion over time revealed enhanced performance of PHBN scaffolds. Our research suggests that scaffold made of PHB nanoparticles could serve as a superior material for tissue engineering applications than its native form.

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment.

Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core-shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size-shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size-shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications.

Fabricated polyhydroxyalkanoates blend scaffolds enhance cell viability and cell proliferation.

For tissue engineering applications, cell adhesion and proliferation are crucial factors, and blending polymers is one of the most effective ways to create a biocompatible scaffold with desired properties. In order to create new potential porous, biodegradable scaffolds using salt leaching technique, poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were blended in different ratios. SEM, BET, FTIR, and water contact angle measurements were used to analyze the scaffolds' porous surface, surface area, and roughness, chemical interaction, and hydrophilicity. Additionally, a hemolysis assay revealed that the mixtures were hemocompatible and had no impact on red blood cells. Different cells- Vero, Hela and MDBK cell lines cultured on the porous mats of these biopolymeric scaffolds exhibited significant increase in cell viability and attachment over time. The overall finding was that blended scaffolds exhibited reduced crystallinity, diverse porosity, higher surface area and hydrophilicity, and better cell viability, proliferation and adhesion. Our findings imply that a blended scaffold could be more suitable for use in tissue engineering applications.

In vitro and in vivo evaluation of kinase and protease inhibitors against Trypanosoma evansi.

Trypanosoma evansi is a causative agent of chronic wasting and fatal disease of livestock and wild animals known as surra. In this study, repurposing approach based on drug target was used to investigate the efficacy of kinase inhibitors (Barasertib-HQPA, BAR and Palbociclib isethionate, PAL) and protease inhibitors (Z-pro-prolinal, Z-PRO and Leupeptin hemisulphate, LEU) against T. evansi in HMI-9 medium. BAR, PAL and Z-PRO exhibited IC50 values of 13.52 µM, 0.6375 µM and 63.20 µM against T. evansi in terms of growth inhibition, in the contrary, LEU failed to exhibit a significant growth inhibition at any time interval. Furthermore, oligopeptidase B and aurora kinase genes of T. evansi were targeted to determine the effect of these drugs on quantitative mRNA expression, which showed significant (p < 0.01) up-regulation of both genes in the BAR and PAL-exposed population at 12 h of exposure, whereas, Z-PRO showed only significant (p < 0.05) up-regulation of aurora kinase gene at 12 h interval. In cytotoxicity assay, BAR exhibited 52% and 41% cytotoxicity at 50 µM concentration (about five folds the IC50 value) on equine PBMC's and Vero cell line, respectively. Similarly, the cytotoxicity of 25% and 24% were recorded at 10 µM concentration (about ten folds to the IC50 value) of PAL in equine PBMC's and Vero cell line, respectively. Of these, BAR and PAL, which were found effective under in vitro trials, raised the longevity of mice at higher doses during in vivo trials. Data generated showed that kinase inhibitors have higher potential to explore therapeutic molecules against surra organism.

A Surgical Approach in the Management of Mucormycosis in Trauma Patients.

Introduction: Fungal infections are rare occurrence in the oral cavity. They are most often seen in other medical conditions such as the immunocompromised states, diabetes, on immunosuppressants, and more recently, among the COVID patients. There are various ways that are employed to manage these infections. The most usual of fungal infection in these conditions is mucormycosis, also called as zygomycosis. Hence, in our study, we aim to evaluate the management of the fungal infection mucormycosis in trauma patients by the surgical approach. Materials and Methods: We piloted a retrospective observational study among 50 subjects who were admitted to the department with oral fungal infections with mucormycosis. We analyzed various clinical and demographic parameters among the subjects. The data thus obtained were analyzed with proper statistical tools deliberating P < 0.05 as significant. Results: We observed that among the 50 subjects, the mean age was 41 ± 1.7 years. There was no significant difference between the genders and the age groups. The most common reason for the oral involvement was uncontrolled diabetes. This was followed by malignancy, specifically leukemia, AIDS, and COVID. The most common site of the involvement was the palate, followed by the mandibular region. All the subjects tested positive for the fungal hyphae of Rhizopus arrhizus which was the most common of the species. The surgical debridement along with the medical management showed satisfactory results, while one death was noted in our study. Conclusion: Although rare, oral involvement in the fungal infection with the mucormycosis is often easily managed when diagnosed early. The proper surgical debridement is the best method of treatment along with the appropriate medications. The management of the underlying medical conditions is the primary key for the success of the treatments.

Mechanism of Action and Implication of Naphthoquinone as Potent Anti-trypanosomal Drugs.

Naphthoquinone is a heterocyclic moiety whose natural derivatives are present as bioactive compounds in many plants and have stimulated a resurgence of interest in the past decades due to their wide range of pharmacological activities. Naphthoquinone agents have dynamic pharmacophores and privileged sub-structures in the chemistry of medicine. They have received much interest in drug discovery as trypanocidal because naphthoquinone and their derivatives revealed massive significance potential against the trypanosomes. Among natural naphthoquinones, lapachol, ß-lapachone and its α-isomer exhibited useful trypanocidal activities. Some naphthoquinones have already been used commercially as an antiparasitic agent. Several naphthoquinones with diverse structural motifs have been synthesized and evaluated mainly against Trypanosoma cruzi and some studies have also been reported against Trypanosoma brucei and Trypanosoma evansi. This review summarized various mechanisms of action of naphthoquinone like reductive activation of quinone by the production of the semiquinone, generation of reactive oxygen species and free radicals such as superoxide anion radical and H2O2, and oxidative stress in the parasite. The information assembled in this review will help to understand the mechanism behind the activity and may also be useful to find the bio-efficacy of naphthoquinone compounds upon substitution against trypanosomatids.

Natural naphthoquinones and their derivatives as potential drug molecules against trypanosome parasites.

Over the past decades, a number of 1,4-naphthoquinones have been isolated from natural resources and several of naphthoquinone derivatives with diverse structural motif have been synthesized; they possess a multitude of biochemical properties and modulate numerous pharmacological roles that offer new targets for addressing the challenges pertaining to novel drug developments. Among natural naphthoquinones, lapachol, α-lapachone, ß-lapachone, lawsone, juglone, and plumbagin have been evaluated for its potential as antitrypanosomal activities. The chemotherapeutic drugs available for combating human trypanosomiasis, that is, American trypanosomiasis and African trypanosomiasis caused by Trypanosoma cruzi and Trypanosoma brucei, respectively, and animal tripanosomosis caused by Trypanosoma evansi have a problem of drug resistance and several toxic effect. Therefore, search of alternative effective drug molecules, without toxic effects, have enthused the researchers for searching new drug entity with potential clinical efficacy. In the search for new antitrypanosomal compound, this review focuses on different natural quinones and their synthetic derivatives associated with antitrypanosomal studies. In this context, this review will be useful for the development of new antitrypanosomal drugs mainly based on different structural modification of natural and synthetic naphthoquinones.

Scaffolds the backbone of tissue engineering: Advancements in use of polyhydroxyalkanoates (PHA).

Our body is built to heal from inside out naturally but wide-ranging medical conditions necessitate the need for artificial assistance, and therefore, something that can assist the body to heal wounds and damaged tissues quickly and efficiently is of utmost importance. Tissue engineering technology helps to regenerate new tissue to replace the diseased or injured one. The technology uses biodegradable porous three-dimensional scaffolds for mimicking the structure and functions of the natural extracellular matrix. The material and design of scaffolds are critical areas of biomaterial research. Biomaterial-based three-dimensional structures have been the most promising material to serve as scaffolds for seeding cells, both in vivo and in vitro. One such material is polyhydroxyalkanoates (PHAs) which are thermoplastic biopolyesters that are highly suitable for this purpose due to their enhanced biocompatibility, biodegradability, thermo-processability, diverse mechanical properties, non-toxicity and natural origin. Moreover, they have tremendous possibilities of customization through biological physical and chemical modification as well as blending with other materials. They are being used for several tissue engineering applications such as bone graft substitute, cardiovascular patches, stents, for nerve repair and in implantology as valves and sutures. The present review overviews usage of a multitude of PHA-based biomaterials for a wide range of tissue engineering applications, based on their properties suitable for the specific applications.

Gum-based nanocapsules comprising naphthoquinones enhance the apoptotic and trypanocidal activity against Trypanosoma evansi.

Nanoencapsulation is a promising approach to enhance the therapeutic potential of a drug. Herein, three selected naphthoquinone (NTQ) derivatives, based on the IC50 value against Trypanosoma evansi, were encapsulated using gum damar as biocompatible and biodegradable natural gum via nanoprecipitation method. Nanoformulation of NTQs (NNTQs) was less than 150 nm in size, was found to be stable and released the drug in a sustained manner. All the three NNTQs exhibited significant antitrypanosomal effect and morphological changes at approximately two to three times lesser drug concentrations. The nanoformulations exhibited enhanced production of reactive oxygen species (ROS) in the axenic culture of T. evansi and less cytotoxic effect on horse peripheral blood mononuclear cells relative to pure NTQs. As evidenced by flow cytometry, the NNTQs showed dose-dependent and time-dependent increased transition of live cells (AV-PI-) to early apoptotic cells (AV+PI-), late apoptotic cells (AV-PI+), and necrotic cells (AV+PI+) using annexin V/propidium iodide probe analysis. The results concluded that NNTQs induced more ROS, apoptosis and necrotic effects that exhibited more inhibitory effect on the growth of T. evansi with respect to respective NTQ by themselves.

Development of Multiwalled Carbon Nanotube-Based Immunobiosensor for the Detection of Bluetongue Virus.

Bluetongue (BT) disease is a noncontagious disease of domestic and wild ruminants (mainly sheep, cattle, deer) caused by the bluetongue virus (BTV) which is an orbivirus of the Reoviridae family and transmitted by vector Culicoides biting midges. It is a reportable disease of considerable socioeconomic concern and of major importance for the international trade of animals and animal products. Conventional diagnostic methods, such as virus propagation and isolation, immunoassays and also various molecular methods have been developed for the detection of the BTV. Here, we present a novel, rapid and pen-side test for the detection of BTV using multiwalled carbon nanotube (MWCNTs) based immunosensor. Though it is not reported yet. The MWCNTs were prepared, characterized and functionalized with carboxyl group. Viral antibodies were conjugated successfully with functionalized MWCNTs and coated on screen printed carbon electrode (SPCE). These SPCE were evaluated by using electrochemical sensor with an antigen specific to BTV antibodies, resulted in the self-assembled layer of antigen-antibody on the surface of SPCE. The approach described in the present study is a prototype for the development of simple and economic diagnostic tool which will provide the routine screening of BT disease at the door of farmers, thereby increasing the income of farmers by decreasing the cost of diagnosis.

Naphthoquinone derivatives exhibit apoptosis-like effect and anti-trypanosomal activity against Trypanosoma evansi.

Trypanosoma evansi is an extracellular flagellate blood protozoan parasite and an etiological agent of animal trypanosomosis. Presently, only a few drugs are registered and have been used for the treatment of animal trypanosomosis, but they show severe toxic effects and also face the problem of drug resistance. Naphthoquinones (NTQ) are considered as fortunate structures in the field of medicinal chemistry as they have been reported for their antitrypanosomal potential against other trypanosomes-T. brucei and T. cruzi. In the present study, six naphthoquinones (NTQ1-NTQ6) derivatives were evaluated for anti-trypanosomal activity by demonstrating their growth inhibitory effect against T. evansi. All NTQs significantly (p < 0.001) exhibited activity against parasite growth and multiplication with IC50 values of 11.48 µM, 373.6 µM, 12.97 µM, 21.97 µM, 18.19 µM and 5.758 µM but NTQ1, NTQ3 and NTQ6 were selected based on their IC50 value for further studies. The dose-and time-dependent morphological effect on parasite was evaluated including the measurement of reactive oxygen species (ROS) by spectrofluorometery and measurement of apoptosis by flow cytometry. The selected NTQs exhibited a significant production of ROS and displayed a significant AV+ and PI+ labelled cells in the axenic culture of T. evansi than quinapyramine methyl sulphate (QPS), as reference control. NTQs also showed more cytotoxic effect on horse peripheral blood mononuclear cells as compare to QPS. Therefore, we confirmed the antitrypanosomal activity and apoptotic-like mechanism of NTQs in an axenic culture of T. evansi.

Nanotechnology enabled the enhancement of antitrypanosomal activity of piperine against Trypanosoma evansi.

Nanoencapsulation is the promising approach to enhance the therapeutic potential of a drug. In the present investigation, piperine-loaded nanocapsules (NCs) was prepared and evaluated for antitrypanosomal activity against the parasite Trypanosoma evansi, a causative agent of trypanosomiasis. Piperine, a bioactive compound was selected as an alternative for drugs that have been used for the treatment of the disease from decades to overcome the toxic effects or drug resistance effect. Moreover, piperine has reported to possess therapeutic potential against other Trypanosoma spp. and has also been reported to cause reactive oxygen species (ROS) mediated effect in cancer cells that was the other reason for the selection. To date, piperine and its nanoformulations have not been evaluated for their growth inhibitory effect against T. evansi. Piperine-loaded NCs exhibited more significant antitrypanosomal effect at approximately three-times less IC50 value 5.04 µM as compared to piperine (IC50-14.45 µM). Moreover, increased production of reactive oxygen species observed in the case of piperine-loaded NCs as that of pure piperine in the axenic culture of T. evansi. Furthermore, different concentrations of piperine-loaded NCs showed less cytotoxicity on horse peripheral blood mononuclear cells as liken to pure piperine. In conclusion, our results demonstrated that piperine-loaded NCs induced more generation of ROS that contributed inhibitory effect on the growth of Trypanosoma evansi as compared to pure drug.

Drug-induced reactive oxygen species-mediated inhibitory effect on growth of Trypanosoma evansi in axenic culture system.

Trypanosoma evansi, an extracellular haemoflagellate, has a wide range of hosts receptive and susceptible to infection, in which it revealed highly inconsistent clinical effects. Drugs used for the treatment of trypanosomosis have been utilized for more than five decades and have several problems like local and systemic toxicity. In the present investigation, imatinib and sorafenib were selected as drugs as they are reported to have the potential to cause reactive oxygen species (ROS)-mediated effect in cancer cells. Both have also been reported to have potential against T. brucei, T. cruzi and Leishmania donovani. To date, imatinib and sorafenib have not evaluated for their growth inhibitory effect against T. evansi. Imatinib and sorafenib showed significant (p < 0.001) inhibition on parasite growth and multiplication with IC50 (50% inhibitory concentration) values 6.12 µM and 0.33 µM respectively against T. evansi. Both the drug molecules demonstrated for the generation of ROS in T. evansi and were found up to 65% increased level of ROS as compared with negative control in the axenic culture system. Furthermore, different concentrations of imatinib and sorafenib were found non-toxic on horse peripheral blood mononuclear cells and Vero cell lines. Also, in conclusion, our results demonstrated that imatinib- and sorafenib-induced generation of ROS contributed inhibitory effect on the growth of Trypanosoma evansi in an axenic culture system.

Bioengineered Polymer/Composites as Advanced Biological Detection of Sorbitol: An Application in Healthcare Sector.

Bioengineered polymers and nanomaterials have emerged as promising and advanced materials for the fabrication and development of novel biosensors. Nanotechnology-enabled biosensor methods have high sensitivity, selectivity and more rapid detection of an analyte. Biosensor based methods are more rapid and simple with higher sensitivity and selectivity and can be developed for point-of-care diagnostic testing. Development of a simple, sensitive and rapid method for sorbitol detection is of considerable significance to efficient monitoring of diabetes-associated disorders like cataract, neuropathy, and nephropathy at initial stages. This issue encourages us to write a review that highlights recent advancements in the field of sorbitol detection as no such reports have been published till the date. The first section of this review will be dedicated to the conventional approaches or methods that had been playing a role in detection. The second part focused on the emerging field i.e. biosensors with optical, electrochemical, piezoelectric, etc. approaches for sorbitol detection and the importance of its detection in healthcare application. It is expected that this review will be very helpful for readers to know the different conventional and recent detection techniques for sorbitol at a glance.

Antidiabetic activity enhancement in streptozotocin + nicotinamide-induced diabetic rats through combinational polymeric nanoformulation.

Background: The bioactive compounds glycyrrhizin (GL) and thymoquinone (TQ) have been reported for antidiabetic activity in pure and nanoformulation (NF) form. However, the antidiabetic effect of a combined nanoformulation of these two has not been reported in the literature. Here, a combinational nanomedicine approach was investigated to enhance the antidiabetic effects of the two bioactive compounds of GL and TQ (GT), in type 2 diabetic rats in reference to metformin. Methods: Two separately prepared NFs of GL (using polymeric nanoparticles) and TQ (using polymeric nanocapsules) were mixed to obtain a therapeutic cargo of nanomedicine and then characterized with respect to particle size, stability, morphology, chemical interaction, and in vivo behavior. Additionally, NFs were evaluated for their cytotoxic effect on Vero cell lines compared to the pure form. This nanomedicine was administered orally, both independently and in combination (pure form or NF) for 21 successive days to type 2 diabetic rats and the effect assessed in term of body weight, fasting blood-glucose level, and various biochemical parameters (such as lipid-profile parameters and HbA1c). Results: When these nanomedicines were applied in combined rather than individual forms, significant decreases in blood glucose and HbA1c and significant improvements in body weight and lipid profile were observed, despite them containing lower amounts than the pure forms. The treatment of diabetic rats with GL and TQ, when administered independently in either pure or NF forms, did not lead to favorable trends in any studied parameters. Conclusion: The administration of combined GT NFs exhibited significant improvement in studied parameters. Improvements in antidiabetic activity could have been due to a synergistic effect of combined NFs, leading to enhanced absorption of NFs and lesser cytotoxic effects compared to pure bioactive compounds. Therefore, GT NFs demonstrated potential as a new medicinal agent for the management of diabetes.

Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes.

Thymoquinone is a bioactive constituent of Nigella sativa seeds. It has been reported to possess antihyperglycemic effect in rats. However, the effect of nanoformulation (NF) of thymoquinone has not been reported in literature. So, the present study was designed with the aim to investigate the effect of nanoformulation of thymoquinone in streptozotocin-nicotinamide induced type-2 diabetic rats and compare its effect with pure bioactive compound as well as metformin, a standard antidiabetic drug. It is the first study reporting the use of thymoquinone NF against diabetes. Polymeric nanocapsules (NCs) of thymoquinone and metformin were prepared by nanoprecipitation method using gum rosin, a biocompatible polymer. Box-Behnken statistical analysis tool was used for the optimization of polymer and other excipients. The NCs were then characterized with respect to particle size, stability, morphology, and in vitro drug dissolution profiles. Furthermore, thymoquinone (20, 40 & 80 mg/kg), metformin (150 mg/kg) and their nanoformulations (20, 40 & 80 mg/kg for thymoquinone and 80 mg/kg for metformin) per se were administered for 21 successive days to type-2 diabetic rats. Body weight and blood glucose levels were measured every week for 3 weeks. Serum lipid profile and glycosylated hemoglobin were estimated on 22nd day. The nanocapsules were stable, spherical in shape and size was less than 100 nm. Thymoquinone-and metformin-loaded NCs showed sustained release profile as compared to their pure forms. Oral administration of thymoquinone, metformin and their nanoformulations significantly decreased blood glucose level and glycated haemoglobin; and improved the lipid profile of diabetic rats as compared to diabetic control rats. Thymoquinone-loaded NCs (containing 10, 20 and 40 mg of thymoquinone) produced dose-dependent antihyperglycemic effect and this effect was comparable to thymoquinone and metformin. In conclusion, thymoquinone nanocapsules (actually containing half of the doses of thymoquinone) produced better antihyperglycemic effect in type-2 diabetic rats as compared to thymoquinone alone.

Evaluation of anti-diabetic activity of glycyrrhizin-loaded nanoparticles in nicotinamide-streptozotocin-induced diabetic rats.

Glycyrrhizin is an active constituent of the roots and rhizomes of Glycyrrhiza glabra and has anti-hyperglycemic effects. In this study, nanoparticles (NPs) loaded with glycyrrhizin or metformin were evaluated in vivo for their anti-hyperglycemic potency towards type-II diabetes in rats. The NPs were produced via the ionotropic gelation method using the biocompatible polymers chitosan and gum arabic. The polymer concentration was optimized using the 32 factorial method to acquire both minimum particle size and maximum encapsulation efficiency. The NPs were then characterized with respect to particle size, encapsulation efficiency, stability, chemical interactions, and in vitro drug dissolution profiles using spectroscopic and microscopic analysis. Furthermore, glycyrrhizin and metformin and their nanoformulations were administered for 21 successive days to diabetic rats. Glycyrrhizin-loaded NPs had significant anti-diabetic effects even though they contained approximately one quarter of the dosage relative to the pure form.