Microbial production of keratinase from Bacillus velezensis strain MAMA: A novel enzyme for eco-friendly degradation of keratin waste.

Keratin waste has become an increasingly serious environmental and health hazard. Keratin waste is mainly composed of keratin protein, which is one of the most difficult polymers to break down in nature and is resistant to many physical, chemical, and biological agents. With physical and chemical methods being environment damaging and costly, microbial degradation of keratin using keratinase enzyme is of great significance as it is both environment friendly and cost-effective. The aim of this study was to extract and purify keratinase from bacterial species isolated from the soil. Among the organisms, an isolate of Bacillus velezensis, coded as MAMA could break down chicken feathers within 72 hours (h). The isolated strain produced significant levels of keratinase in mineral salt medium by supplying chicken feathers as the sole source of nitrogen and carbon. Feather deterioration was observed with the naked eye, and enzyme activity was evaluated using a spectrophotometric assay. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and zymography results revealed that the keratinase protein produced by Bacillus velezensis had a molecular weight between 40 and 55 kilodalton (kDa).

Biomedical Applications of Green Synthesized Zinc Oxide and Magnesium-Doped Zinc Oxide Nanoparticles Using Aqueous Extract of Ziziphus Oxyphylla Leaves.

Zinc oxide (ZnO) and magnesium-doped zinc oxide (Mg-doped ZnO) nanoparticles (NPs) were synthesized using Ziziphus oxyphylla 's aqueous leaf extract as reducing agent. UV-Vis absorption peaks at 324 nm and 335 nm were indicative of ZnO and Mg-doped ZnO, respectively. FTIR absorption bands observed at 3238, 1043, 1400, 1401, 2186 and 2320 cm -1 suggested the presence of phenols, alcohols, saturated hydrocarbons, and possibly alkynes. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy revealed pure, spherical and agglomerated NPs with average size of 35.9 nm (ZnO) and 56.8 nm (Mg-doped ZnO). Both NPs remained active against all bacterial strains with the highest inhibition zones observed against Proteus vulgaris (21.16±1.25 mm for ZnO and 24.1±0.76 mm for Mg-doped ZnO. EtBr fluorescence (cartwheel assay) indicated efflux pump blockage, suggesting its facilitation in the bacterial growth inhibition. Antioxidant potential, determined via DPPH radical scavenging assay, revealed stronger antioxidant potential for Mg-doped ZnO (IC [Formula: see text]/mL) than pure ZnO (IC [Formula: see text]/mL). Furthermore, both NPs showed antileishmanial activity against Leishmania tropica promastigotes (IC [Formula: see text]/mL for Mg-doped ZnO and 64.34±6.56 for ZnO), while neither NP exhibited significant hemolysis, indicating biocompatibility and further assessment for their drugability.

Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review.

Solid-lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on.

Iron-doped zinc oxide nanoparticles-triggered elicitation of important phenolic compounds in cell cultures of Fagonia indica.

The callus cultures of Fagonia indica could prove as factories for the production of important phytochemicals when triggered through different types of stress. In this study, we initiated callus cultures from healthy stem explants in the presence of iron-doped zinc oxide nanoparticles (Fe-ZnO-NPs). We performed experiments with the callus cultures of F. indica to determine the impact of Fe-ZnO-NPs in concentrations (15.62-250 µg/mL) on biomass accumulation, production of important phenolic and flavonoids, and antioxidative potential. Our results showed that maximum callus biomass [Fresh weight (FW) = 13.6 g and Dry weight (DW) = 0.58 ± 0.01] was produced on day 40 when the media was supplemented with 250 µg/mL Fe-ZnO-NPs. Similarly, maximum total phenolic content (268.36 µg GAE/g of DW) was observed in 40 days old callus added with 125 µg/mL Fe-ZnO-NPs. Maximum total flavonoid content (78.56 µg QE/g of DW) was recorded in 20 days old callus grown in 62.5 µg/mL Fe-ZnO-NPs containing media. Maximum total antioxidant capacity (390.74 µg AAE/g of DW) was recorded in 40 days old callus with 125 µg/mL Fe-ZnO-NPs treated cultures, respectively. Similarly, the highest free radical scavenging activity (93.02%) was observed in callus derived from media having 15.62 µg/mL Fe-ZnO-NPs. The antioxidant potential was observed to have positive correlation with TPC (r = 0.44). HPLC analysis showed that Fe-ZnO-NPs produced compounds (e.g., Epigallocatechin gallate) that were either absent or in lesser quantities in the control group. These results showed that Fe-ZnO-NPs elicitors could increase the biomass and activate secondary metabolism in F. indica cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11240-021-02123-1.

Plant in vitro Culture Technologies; A Promise Into Factories of Secondary Metabolites Against COVID-19.

The current pandemic has caused chaos throughout the world. While there are few vaccines available now, there is the need for better treatment alternatives in line with preventive measures against COVID-19. Along with synthetic chemical compounds, phytochemicals cannot be overlooked as candidates for drugs against severe respiratory coronavirus 2 (SARS-CoV-2). The important role of secondary metabolites or phytochemical compounds against coronaviruses has been confirmed by studies that reported the anti-coronavirus role of glycyrrhizin from the roots of Glycyrrhiza glabra. The study demonstrated that glycyrrhizin is a very promising phytochemical against SARS-CoV, which caused an outbreak in 2002-2003. Similarly, many phytochemical compounds (apigenin, betulonic acid, reserpine, emodin, etc.) were isolated from different plants such as Isatis indigotica, Lindera aggregate, and Artemisia annua and were employed against SARS-CoV. However, owing to the geographical and seasonal variation, the quality of standard medicinal compounds isolated from plants varies. Furthermore, many of the important medicinal plants are either threatened or on the verge of endangerment because of overharvesting for medicinal purposes. Therefore, plant biotechnology provides a better alternative in the form of in vitro culture technology, including plant cell cultures, adventitious roots cultures, and organ and tissue cultures. In vitro cultures can serve as factories of secondary metabolites/phytochemicals that can be produced in bulk and of uniform quality in the fight against COVID-19, once tested. Similarly, environmental and molecular manipulation of these in vitro cultures could provide engineered drug candidates for testing against COVID-19. The in vitro culture-based phytochemicals have an additional benefit of consistency in terms of yield as well as quality. Nonetheless, as the traditional plant-based compounds might prove toxic in some cases, engineered production of promising phytochemicals can bypass this barrier. Our article focuses on reviewing the potential of the different in vitro plant cultures to produce medicinally important secondary metabolites that could ultimately be helpful in the fight against COVID-19.

Therapeutic potential of medicinal plants against COVID-19: The role of antiviral medicinal metabolites.

There are numerous trials underway to find treatment for the COVID-19 through testing vaccines as well as existing drugs. Apart from the many synthetic chemical compounds, plant-based compounds could provide an array of \suitable candidates for testing against the virus. Studies have confirmed the role of many plants against respiratory viruses when employed either as crude extracts or their active ingredients in pure form. The purpose of this review article is to highlight the importance of phytomedicine against COVID-19. The main aim is to review the mechanistic aspects of most important phytochemical compounds that have showed potential against coronaviruses. Glycyrrhizin from the roots of Glycyrrhiza glabra has shown promising potential against the previously epidemic coronavirus, SARS-CoV. Other important plants such as Artemisia annua, Isatis indigotica, Lindera aggregate, Pelargonium sidoides, and Glychirrhiza spp. have been employed against SARS-CoV. Active ingredients (e.g. emodin, reserpine, aescin, myricetin, scutellarin, apigenin, luteolin, and betulonic acid) have shown promising results against the coronaviruses. Phytochemicals have demonstrated activity against the coronaviruses through mechanisms such as viral entry inhibition, inhibition of replication enzymes and virus release blockage. However, compared to synthetic drugs, phytomedicine are mechanistically less understood and should be properly evaluated before application. Nonetheless, phytochemicals reduce the tedious job of drug discovery and provide a less time-consuming alternative for drug testing. Therefore, along with other drugs currently tested against COVID-19, plant-based drugs should be included for speedy development of COVID-19 treatment.

A Review of Microbial Mediated Iron Nanoparticles (IONPs) and Its Biomedical Applications.

Nanotechnology is a booming avenue in science and has a multitude of applications in health, agriculture, and industry. It exploits materials' size at nanoscale (1-100 nm) known as nanoparticles (NPs). These nanoscale constituents are made via chemical, physical, and biological methods; however, the biological approach offers multiple benefits over the other counterparts. This method utilizes various biological resources for synthesis (microbes, plants, and others), which act as a reducing and capping agent. Among these sources, microbes provide an excellent platform for synthesis and have been recently exploited in the synthesis of various metallic NPs, in particular iron. Owing to their biocompatible nature, superparamagnetic properties, small size efficient, permeability, and absorption, they have become an integral part of biomedical research. This review focuses on microbial synthesis of iron oxide nanoparticles using various species of bacteria, fungi, and yeast. Possible applications and challenges that need to be addressed have also been discussed in the review; in particular, their antimicrobial and anticancer potentials are discussed in detail along with possible mechanisms. Moreover, some other possible biomedical applications are also highlighted. Although iron oxide nanoparticles have revolutionized biomedical research, issues such as cytotoxicity and biodegradability are still a major bottleneck in the commercialization of these nanoparticle-based products. Addressing these issues should be the topmost priority so that the biomedical industry can reap maximum benefit from iron oxide nanoparticle-based products.

Synergistic response of physicochemical reaction parameters on biogenesis of silver nanoparticles and their action against colon cancer and leishmanial cells.

Physicochemical parameters include pH, temperature, the concentration of the AgNO3, ratio of reactants, agitation and incubation period that act synergistically and provide a steering force to modulate the biogenesis of nanoparticles by influencing the molecular dynamics, reaction kinetics, protein conformations, and catalysis. The current study involved the bio-fabrication of silver nanoparticles (SNPs) by using the reducing abilities of Mentha longifolia (L.) L. leaves aqueous extract. Spectrophotometric analysis of various biochemical reactions showed that 3 mM of AgNO3 at 120 °C in an acidic pH when mixed in 1-9 ratio of plant extract and AgNO3 respectively, are the optimised conditions for SNPs synthesis. Different analytical techniques confirmed that the nanoparticles are anisotropic and nearly spherical and have a size range of 10-100 nm. The ∼10 µg/ml of SNPs killed ∼66% of Leishmania population and IC50 was measured at 8.73 µg/ml. SRB assay and Annexin V apoptosis assay results showed that the plant aqueous extract and SNPs are not active against HCT116 colon cancer cells and no IC50 (80% survival) was reported. ROS generation was quantified at 0.08 Φ, revealed that the SNPs from M. longifolia can generate free radicals and no photothermal activity was recorded which makes them non-photodynamic.

Green Synthesis of Cerium Oxide Nanoparticles (CeO2 NPs) and Their Antimicrobial Applications: A Review.

During the last decade green synthesized cerium oxide nanoparticles (CeO2 NPs) attracted remarkable interest in various fields of science and technology. This review, explores the vast array of biological resources such as plants, microbes, and other biological products being used in synthesis of CeO2 NPs. It also discusses their biosynthetic mechanism, current understandings, and trends in the green synthesis of CeO2 NPs. Novel therapies based on green synthesized CeO2 NPs are illustrated, in particular their antimicrobial potential along with attempts of their mechanistic elucidation. Overall, the main objective of this review is to provide a rational insight of the major accomplishments of CeO2 NPs as novel therapeutics agents for a wide range of microbial pathogens and combating other diseases.

Green synthesized selenium doped zinc oxide nano-antibiotic: synthesis, characterization and evaluation of antimicrobial, nanotoxicity and teratogenicity potential.

A facile, green synthesis of selenium doped zinc oxide nano-antibiotic (Se-ZnO-NAB) using the Curcuma longa extract is reported to combat the increased emergence of methicillin-resistant Staphylococcus aureus (MRSA). The developed Se-ZnO-NAB were characterized for their physicochemical parameters and extensively evaluated for their toxicological potential in an animal model. The prepared Se-ZnO-NABs were characterized via Fourier transformed infrared spectroscopy to get functional insight into their surface chemistry, scanning electron microscopy revealing the polyhedral morphology with a size range of 36 ± 16 nm, having -28.9 ± 6.42 mV zeta potential, and inductively coupled plasma optical emission spectrometry confirming the amount of Se and Zn to be 14.43 and 71.70 mg L-1 respectively. Moreover, the antibacterial activity against MRSA showed significantly low minimum inhibitory concentration at 6.2 µg mL-1 when compared against antibiotics. Also, total protein content and reactive oxygen species production in MRSA, under the stressed environment of Se-ZnO-NAB, significantly (p < 0.05) decreased compared to the negative control. Moreover, the results of acute oral toxicity in rats showed moderate variations in blood biochemistry and histopathology of vital organs. The teratogenicity and fetal evaluations also revealed some signs of toxicity along with changes in biochemical parameters. The overall outcomes suggest that Se-ZnO-NAB can be of significant importance for combating multi-drug resistance but must be used with extreme caution, particularly in pregnancy, as moderate toxicity was observed at a toxic dose of 2000 mg kg-1.

Reactive oxygen species generating photosynthesized ferromagnetic iron oxide nanorods as promising antileishmanial agent.

Aim: To investigate the photodynamic therapeutic potential of ferromagnetic iron oxide nanorods (FIONs), using Trigonella foenum-graecum as a reducing agent, against Leishmania tropica. Materials & methods: FIONs were characterized using ultraviolet visible spectroscopy, x-ray diffraction and scanning electron microscopy. Results: FIONs showed excellent activity against L. tropica promastigotes and amastigotes (IC50 0.036 ± 0.003 and 0.072 ± 0.001 µg/ml, respectively) upon 15 min pre-incubation light-emitting diode light (84 lm/W) exposure, resulting in reactive oxygen species generation and induction of cell death via apoptosis. FIONs were found to be highly biocompatible with human erythrocytes (LD50 779 ± 21 µg/ml) and significantly selective (selectivity index >1000) against murine peritoneal macrophages (CC50 102.7 ± 2.9 µg/ml). Conclusion: Due to their noteworthy in vitro antileishmanial properties, FIONs should be further investigated in an in vivo model of the disease.

Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches.

BACKGROUND: Liver cancer is a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed. METHODS: The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine kinase. RESULTS: In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9 µg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 µg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 µg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5µg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation of two compounds which were characterized as para-methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 µg/ml followed by 2 with IC50 18.52 ± 1.9 µg/ml. DMSO was used as a negative control and doxorubicin as a reference standard (IC50 1.3 ± 0.21 µg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity. CONCLUSION: This study revealed that the plant extracts and isolated compounds possess promising antiproliferative activity against HepG-2 cell lines via apoptotic cell death.

Photo-inactivation of bacteria in hospital effluent via thiolated iron-doped nanoceria.

Hospital wastewater is a major contributor of disease-causing microbes and the emergence of antibiotic resistant bacteria. In this study, thiolated iron-doped nanoceria was synthesised and tested for killing of microbes from hospital effluent. These particles were designed to inhibit the efflux pumps of the bacteria found in hospital effluent with further ability to activate in visible light via iron doping thus generating tunable amount of reactive oxygen species (ROS). The quantum yield of the ROS generated by the nanoceria was 0.67 while the ROS types produced were singlet oxygen (36%), hydroxyl radical (31%) and hydroxyl ions (32%), respectively. The particles were initially synthesised through green route using Foeniculum vulgare seeds extract and were annealed at 200°C and further coated with thiolated chitosan to enhance the solubility and efflux pump inhibition. X-ray diffraction confirmed the polycrystalline nature of nanoparticles and uniform spherical shape with 30 nm size, confirmed by scanning electron microscope. The nanoparticles exhibited 100% bactericidal activity at 100 µg/mL against all the isolated bacteria. The enhanced bactericidal effect of iron-doped nanoceria could be attributed to efflux inhibition via thiolated chitosan as well as the production of ROS upon illumination in visible light, causing oxidative stress against microbes found in hospital effluent.

Plant-based gold nanoparticles; a comprehensive review of the decade-long research on synthesis, mechanistic aspects and diverse applications.

The worldwide focus on research in the field of green nanotechnology has resulted in the environmentally and biologically safe applications of a diversity of nanomaterials. Nanotechnology, in general, implies the production of nanoparticles having different but regular shapes, sizes, and properties. A lot of studies have been conducted on the synthesis of metal nanoparticles through biological, chemical, and physical methods. Owing to its safety, both environmental and in vivo, as well as the ease of synthesis, biogenic routes especially the plant-based synthesis of metal nanoparticles has been preferred as the best strategy. Among the metal nanoparticles, gold nanoparticles are recognized as the most potent, biocompatible and environment-friendly. A decade of research work has attempted the production of gold nanoparticles mediated by different parts of various plants. Further, these nanoparticles have been engineered through modification in the sizes and shapes for attaining enhanced activity and optimal performance in many different applications including biomedical, antimicrobial, diagnostics and environmental applications. This article reviews the fabrication strategies for gold nanoparticles via plant-based routes and highlights the diversity of the applications of these materials in bio-nanotechnology. The review article also highlights the recent developments in the synthesis and optical properties of gold nanoparticles.

ß-Sitosterol from Ifloga spicata (Forssk.) Sch. Bip. as potential anti-leishmanial agent against leishmania tropica: Docking and molecular insights.

The current study was aimed to evaluate the anti-leishmanial potentials of ß-sitosterol isolated from Ifloga spicata. The anti-leishmanial potential of ß-sitosterol is well documented against Leishmania donovani and Leishmania amazonensis but unexplored against Leishmania tropica. Structure of the compound was elucidated by FT-IR, mass spectrometry and multinuclear (1H and 13C) magnetic resonance spectroscopy. The compound was evaluated for its anti-leishmanial potentials against L. tropica KWH23 using in vitro anti-promastigote, DNA interaction, apoptosis, docking studies against leishmanolysin (GP63) and trypanothione reductase (TR) receptors using MOE 2016 software. ß-sitosterol exhibited significant activity against leishmania promastigotes with IC50 values of 9.2 ±â€¯0.06 µg/mL. The standard drug glucantaime showed IC50 of 5.33 ±â€¯0.07 µg/mL. Further mechanistic studies including DNA targeting and apoptosis induction via acridine orange assay exhibited promising anti-leishmanial potentials for ß-sitosterol. Molecular docking with leishmanolysin (GP63) and trypanothione reductase (TR) receptors displayed the binding scores of ß-sitosterol with targets TR and GP63 were -7.659 and -6.966 respectively. The low binding energies -61.54 (for TR) and -33.24 (for GP63) indicate that it strongly bind to the active sites of target receptors. The results confirmed that ß-sitosterol have considerable anti-leishmanial potentials and need further studies as potential natural anti-leishmanial agent against L. tropica.

Photo-inactivation and efflux pump inhibition of methicillin resistant Staphylococcus aureus using thiolated cobalt doped ZnO nanoparticles.

Multidrug resistance (MDR) in bacteria is a major concern these days. One of the reasons is the mutation in efflux pump that prevents the retention of antibiotics and drugs in the bacterial cell. The current work is a step to overcome MDR in bacteria via inhibition of efflux pump and further photoinhibition by thiolated chitosan coated cobalt doped zinc oxide nanoparticles (Co-ZnO) in visible light. Co-ZnO were synthesized in a size range of 40-60 nm. Antibacterial activity of the Co-ZnO against methicillin resistant Staphylococcus aureus (MRSA) was found 100% at a concentration of 10 µg/ml upon activation in sunlight for 15 min. Interestingly, it was found that cobalt as a dopant was able to increase the photodynamic and photothermal activity of Co-ZnO, as in dark conditions, there was only 3-5% of inhibition at 10 µg/ml of nanoparticle concentration. Upon excitation in light, these nanoparticles were able to generate reactive oxygen species (ROS) with a quantum yield of 0.23 ±â€¯0.034. The nanoparticles were also generating heat, Because of the magnetic nature, thus helping in more killing. Thiolated chitosan further helped in blocking the efflux pump of MRSA. The current nanoparticles were also found biocompatible on human red blood cells (LD50 = 214 µg/ml). These data suggest that the MRSA killing ability was facilitated through efflux inhibition and oxidative stress upon excitation in visible light hence, were in accordance with previous findings.

Formulation and Characterization of a Self-Emulsifying Drug Delivery System (SEDDS) of Curcumin for the Topical Application in Cutaneous and Mucocutaneous Leishmaniasis.

BACKGROUND: Leishmaniasis, which is classified by the World Health Organization (WHO) as one of the Neglected Tropical Diseases (NTDs) faces several challenges in terms of successful chemotherapy and novel drug developments. OBJECTIVE: The aim of the present study was to develop a Self-Emulsifying Drug Delivery System (SEDDS) for the hydrophobic polyphenol pigment curcumin to enable it for its potential use in cutaneous and mucocutaneous leishmaniasis. METHODS: Two Curcumin-loaded formulations SNEDD-A and B, were developed. Both were characterized by the droplet size, PDI and zeta potential and evaluated for the cytotoxicity on Caco-2 cell lines and through hemolysis test on red blood cells. The spreading potential of the formulations was checked over buccal mucosa and damaged skin model. Antileishmanial activities were performed against promastigote, axenic amastigote and macrophage harbored amastigotes of Leishmania tropica parasite. RESULTS: SNEDDS-A and B had minor differences in physical characteristics. In the toxicological assay, the viability of the Caco-2 cells was 87.5 % for SNEDDS-A and 88.9% for SNEDDS-B while both caused 1-2% hemolysis. Both had remarkable spreading potential, covering 8cm2 of buccal mucosa and damaged the skin for less than 45 minutes. The Antileishmanial activities of the SNEDDS-A in terms of IC50 were 0.13 µg/ml and 0.25 µg/ml against promastigote and amastigote, respectively while IC50 values of SNEDDS-B were 0.18 µg/ml and 0.27 µg/ml against promastigote and amastigote, respectively. Both the formulations killed 100% of the macrophage harbored Leishmania tropica parasites at a concentration of 4.4 µg/ml. CONCLUSION: Our results demonstrate that both the SEDDS formulations of curcumin have the potential to provide a promising tool for curcumin for its use through topical routes in the treatment of cutaneous and mucocutaneous leishmaniasis.

Polymeric nanocapsules embedded with ultra-small silver nanoclusters for synergistic pharmacology and improved oral delivery of Docetaxel.

Despite of the remarkable cytotoxic and imaging potential of ultra-small metal nanoclusters, their toxicity-free and targeted delivery to cancerous cells remains a substantial challenge that hinders their clinical applications. In this study, a polymeric scaffold was first synthesized by grafting folic acid and thiol groups to chitosan (CS) for cancer cell targeting and improved gastric permeation. Furthermore, silver nanocluster (Ag NCs) were synthesized in situ, within CS scaffold by microwave irradiation and core-shell nanocapsules (NCPs) were prepared with hydrophobic docetaxel (DTX) in the core and Ag NCs embedded CS in the shell. A significant cytotoxicity synergism (~300 folds) was observed for DTX with co-delivery of Ag NCs against breast cancer MDA-MB-231 cells. Following oral administration, the DTX-Ag-NCPs increased bioavailability due to enhanced drug transport across gut (9 times), circulation half-life (~6.8 times) and mean residence time (~6.7 times), as compared to the control DTX suspension. Moreover, 14 days acute oral toxicity of the DTX-Ag-NCPs was performed in mice and evaluated for changes in blood biochemistry parameters, organ to body weight index and histopathology of liver and kidney tissues that revealed no significant evidence of toxicity suggesting the safety and efficiency of the DTX-Ag-NCPs as hybrid nanocarrier for biocompatible delivery of metal nanoclusters.

Design of mannosylated oral amphotericin B nanoformulation: efficacy and safety in visceral leishmaniasis.

The aim of this study was to evaluate mannose-anchored thiolated chitosan (MTC) based nanocarriers (NCs) for enhanced permeability, improved oral bioavailability and anti-parasitic potential of amphotericin B (AmB). Transgenic Leishmania donovani parasites expressing red fluorescent protein DsRed2 and imaging-flow cytometry was used to investigate parasitic burdens inside bone marrow-derived macrophages ex vivo. Cytokine estimation revealed that MTC nanocarriers activated the macrophages to impart an explicit immune response by higher production of TNF-α and IL-12 as compared to control. Cells treated with MTC NCs showed a significantly higher magnitude of nitrite and propidium iodide (PI) fluorescence intensity in contrast to cells treated with AmB. Concerning to apparent permeability coefficient (Papp) results, the MTC NCs formulation displayed more specific permeation across the Caco-2 cell monolayer as compared to AmB. The half-life of MTC NCs was about 3.3-fold persistent than oral AmB used as positive control. Also, t oral bioavailability of AmB was increased to 6.4-fold for MTC NCs compared to AmB for positive control. Acute oral evaluation indicated that MTC NCs were significantly less toxic compared to the AmB. Based on these findings, MTC NCs seems to be promising for significant oral absorption and improved oral bioavailability of AmB in leishmaniasis chemotherapy.

Nanomedicine: An effective tool in cancer therapy.

Various types of nanoparticles (NPs) have been used in delivering anticancer drugs to the site of action. This area has become more attractive in recent years due to optimal size and negligible undesirable side effects caused by the NPs. The focus of this review is to explore various types of NPs and their surface/chemical modifications as well as attachment of targeting ligands for tuning their properties in order to facilitate targeted delivery to the cancer sites in a rate-controlled manner. Heme compatibility, biodistribution, longer circulation time, hydrophilic lipophilic balance for high bioavailability, prevention of drug degradation and leakage are important in transporting drugs to the targeted cancer sites. The review discusses advantages of polymeric, magnetic, gold, and mesoporous silica NPs in delivering chemotherapeutic agents over the conventional dosage formulations along with their shortcomings/risks and possible solutions/alternatives.