Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing.

Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-ß, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.

Theranostic Approach for the Management of Osteoporosis.

Osteoporosis (OP) is a bone-metabolic disorder, causing micro-architecture degeneration and a decrease in bone density. Nutritional deficiency, i.e., calcium, vitamin D, and hormonal imbalances are the primary cause for the occurrence of OP. Although conventional diagnostic techniques and therapies are available and found to be effective only at a later stage, though still lack prevention strategies. Thus, the patients tend to suffer incidence of fractures and many difficulties to manage their day-to-day activities at an elderly stage. Numerous nanomaterial(s) possessing unique physicochemical, optical, and electrical properties are reported nowadays to be employed for both early-stage detections of disease and its treatment. Amongst these nanomaterials, superparamagnetic iron oxide nanoparticles (SPIONs) possessing strong magnetic susceptibility, less in vivo toxicity, and surface functionalities are extensively employed for MRI contrast imaging agents in the area of disease diagnosis, and drug delivery tools for various therapies. Therefore, this review highlights the pathophysiology of OP, conventional techniques of diagnosis, and the application of SPIONs for diagnostic and treatment purposes of osteoporosis.

Identification and characterization of stress degradation products of febuxostat employing ultra-performance liquid chromatography-ultraviolet/photodiode array and liquid chromatography-mass spectrometry/time-of-flight studies.

RATIONALE: Febuxostat (FEB) is a xanthine oxidase inhibitor approved by the U.S. Food and Drug Administration for long-term treatment of gout and hyperuricemia. There were no reports on identification and characterization of stress degradation products of the drug. METHODS: FEB was subjected to forced decomposition conditions such as hydrolysis (neutral, acidic, and alkaline), oxidation, photolysis, and thermal stress, per the ICH guideline Q1A(R2). The degradation products formed were subjected to ultra-performance liquid chromatography (UPLC) on a C18 Kinetex column (100 × 4.6 mm, 2.6 µm) using isocratic elution method. Detection wavelength was 317 nm. The developed method was extended to UPLC-mass spectrometry/time of flight (MS/TOF) studies to identify and characterize the degradation products. RESULTS: The drug exhibited significant degradation under alkaline/neutral hydrolytic, alkaline/acidic photolytic, and oxidative conditions, whereas it remained stable under acid hydrolytic, neutral photolytic, and thermal conditions. In total, eight degradation products (I-VIII) were formed, which could be adequately determined from the drug using the developed UPLC method. Of the eight degradation products identified from the liquid chromatography-ultraviolet (LC-UV) chromatogram, five (III and IV and VI-VIII) could be characterized using their MS/TOF spectral data. The degradation pathway leading to the formation of the products was postulated, and this is not reported so far. CONCLUSIONS: Forced degradation studies were conducted on FEB, and the degradation products produced were identified by their mass spectral data obtained using LC-MS studies.

A glass matrices-assisted quantum dots-based biosensor for selective capturing and detection of Escherichia coli.

Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 µL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.

Development of magnetic nanoparticle assisted aptamer-quantum dot based biosensor for the detection of Escherichia coli in water samples.

The contamination of food and potable water with microorganisms may cause food-borne and water-borne diseases. The common contaminants include Escherichia coli (E. coli), Salmonella sp. etc. The conventional methods for monitoring the water quality for the presence of bacterial contaminants are time-consuming, expensive, and not suitable for rapid on-spot detection in field conditions. In the current study, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and conjugated with E. coli specific Aptamer I to detect E. coli cells qualitatively as well as quantitatively. The sludge consisting of E. coli- SPION complex was separated via magnetic separation. The presence of E. coli cells was confirmed with the help of standard techniques and confocal laser scanning microscopy (CLSM) employing Aptamer II conjugated CdTe-MPA quantum dots (QDs). Finally, an ATmega 328P prototype biosensor based on Aptamer II conjugated CdTe MPA QDs exhibited quantitative and qualitative abilities to detect E.coli. This prototype biosensor can even detect low bacterial counts (up to 1 × 102 cfu) with the help of a photodiode and plano-convex lens. Further, the prototype biosensor made up of ultraviolet light-emitting diode (UV LED), liquid crystal display (LCD) and ATmega328Pmicrocontroller offers on-spot detection of E.coli in water samples with high resolution and sensitivity. Similarly, this in-house developed prototype biosensor can also be utilized to detect bacterial contamination in food samples.

Anticancer Biosurfactant-Loaded PLA-PEG Nanoparticles Induce Apoptosis in Human MDA-MB-231 Breast Cancer Cells.

Despite various advancements in cancer therapies, treating cancer efficiently without side effects is still a major concern for researchers. Anticancer drugs from natural sources need to be explored as a replacement for chemo drugs to overcome their limitations. In our previous studies, isolation, characterization, and anticancer properties of a novel biosurfactant from Candida parapsilosis were reported. In this study, we report the cytotoxicity of the polymeric nanoparticles of this novel biosurfactant toward breast cancer cells. Biosurfactant-encapsulated polymeric nanoparticles of polylactic acid-poly(ethylene glycol) (PLA-PEG) copolymers were synthesized by the double emulsion solvent evaporation method. Folic acid (FA) was used as a targeting ligand to actively deliver the anticancer cargo to the cancer site. The encapsulation efficiency of nanoparticles was observed as 84.9%, and Fickian diffusion was observed as a kinetic model for the release of biosurfactant from nanoparticles. The controlled delivery of the biosurfactant was noticed when encapsulated in PLA-PEG copolymer nanoparticles. Additionally, it was observed that FA enhanced the uptake and cytotoxicity of biosurfactant-loaded nanoparticles in MDA-MB-231 cancer cells compared to biosurfactant-loaded plain nanoparticles. Induction of apoptosis was observed in cancer cells by these nanoparticles. We explore a potential anticancer agent that can be further analyzed for its efficiency and can be used as an alternative tool.

Carbon Based Nanodots in Early Diagnosis of Cancer.

Detection of cancer at an early stage is one of the principal factors associated with successful treatment outcome. However, current diagnostic methods are not capable of making sensitive and robust cancer diagnosis. Nanotechnology based products exhibit unique physical, optical and electrical properties that can be useful in diagnosis. These nanotech-enabled diagnostic representatives have proved to be generally more capable and consistent; as they selectively accumulated in the tumor site due to their miniscule size. This article rotates around the conventional imaging techniques, the use of carbon based nanodots viz Carbon Quantum Dots (CQDs), Graphene Quantum Dots (GQDs), Nanodiamonds, Fullerene, and Carbon Nanotubes that have been synthesized in recent years, along with the discovery of a wide range of biomarkers to identify cancer at early stage. Early detection of cancer using nanoconstructs is anticipated to be a distinct reality in the coming years.

Fluorescent quantum dots: An insight on synthesis and potential biological application as drug carrier in cancer.

Quantum dots (QDs) are nanocrystals of semiconducting material possessing quantum mechanical characteristics with capability to get conjugated with drug moieties. The particle size of QDs varies from 2 to 10 nm and can radiate a wide range of colours depending upon their size. Their wide and diverse usage of QDs across the world is due to their adaptable properties like large quantum yield, photostability, and adjustable emission spectrum. QDs are nanomaterials with inherent electrical characteristics that can be used as drug carrier vehicle and as a diagnostic in the field of nanomedicine. Scientists from various fields are aggressively working for the development of single platform that can sense, can produce a microscopic image and even be used to deliver a therapeutic agent. QDs are the fluorescent nano dots with which the possibilities of the drug delivery to a targeted site and its biomedical imaging can be explored. This review is mainly focused on the different process of synthesis of QDs, their application especially in the areas of malignancies and as a theranostic tool. The attempt is to consolidate the data available for the use of QDs in the biomedical applications.

Evaluation of In Vivo toxicity of Novel Biosurfactant from Candida parapsilosis loaded in PLA-PEG Polymeric Nanoparticles.

The aim of this study was to evaluate the toxicological profile of biosurfactant encapsulated polymeric nanoparticles of Polylactic acid-Polyethylene glycol (PLA-PEG) in mice. Hematological, biochemical and histopathological samples of rodents were evaluated. Mice were selected randomly and divided into 3 treatment groups and one control group. Group I mice served as a control group, Group II were administrated with biosurfactant, Group III were treated with Polymeric nanoparticles of PLA-PEG. Group IV mice were injected with biosurfactant loaded polymeric nanoparticles of PLA-PEG. The formulations were administered intravenously via tail vein with 20 µg/mL dose concentration of biosurfactant. The normal control group was injected with only PBS. Blood samples were collected on 7th, 14th and 21st day and hematological and biochemical assays were performed. After the blood collection, mice were sacrificed for histopathological examination. The results showed that there were no significant difference in hematology parameter between the control and treated group. Some minute, non-significant changes were found in biochemical parameters which were not considered. Histopathological result of selected vital organs revealed that the biosurfactant and/or PLA-PEG polymeric nanoparticles can be considered as safe as no toxicological features were observed in histopathology of tissues. Hence, it can be deliberated that the biosurfactant encapsulated in PLA-PEG copolymeric nanoparticles are non toxic and can provide a safe, suitable platform for biomedical applications in future.

Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness.

Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 106 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN®). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

Safety data on in situ gelling bimatoprost loaded nanovesicular formulations.

In vitro cytotoxicity and in vivo acute and 7 days repeat-dose ocular toxicity studies, were conducted in rabbits, in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines, for bimatoprost loaded nanovesicular aqueous dispersion (BMT-NV) and its in-situ gelling sub-conjunctival implant (BMT-NV-IM). For details on the preparation and evaluation of BMT-NV and its BMT-NV-IM for the control of glaucoma, please refer to 'Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation' (Yadav et al., 2019). The in vivo ocular toxicity was performed only after confirming dermal safety, as required by OECD. Histological evaluation of various ocular tissues, following sub-conjunctival implantation with BMT-NV-IM, was done for ocular tolerance studies.

Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation.

Primary treatment for glaucoma relies on chronic instillation (daily) of intraocular pressure (IOP) lowering eye drops. Present study tends to develop and assess a novel sustained release bimatoprost loaded nanovesicular (BMT-NV) - thermosensitive in-situ gelling implant (BMT-NV-GEL-IM), for subconjunctival delivery. BMT-NVs developed using novel composition and method of preparation, (IPA/700/DEL/2014) and industrially viable methodology were characterized and evaluated comprehensively for ocular suitability. Their incorporation into an in-situ gelling formula was safe (in vitro and in vivo) and stable upon sterilization. Autoclavability was an important consideration, as a preservative-free, single-use BMT-NV-GEL-IM will avoid side- effects associated with repetitive application of drops containing preservatives like benzalkonium chloride (BAK). An extended in vitro release of BMT (80.23%) was observed for 10 days while the IOP lowering effect extended over 2 months with single subconjunctival injection of BMT-NV-GEL-IM in rats. No clinical signs of irritation, inflammation, or infection were observed in any injected eye, throughout the study, as also confirmed by histology. Furthermore, single administration of BMT-NV-GEL as topical drop lowered the IOP over 5 days. Presence of significant diffuse fluorescence in confocal microscopy of internal eye tissues post-in vivo application, as subconjunctival implant, even after 2 month and eye drops upto1 week provide direct evidence of successful sustained delivery. We thus provide an improved modality for antiglaucoma medication in patients who are challenged to adhere to a regimen of daily eye drops.

Development of biosurfactant-based graphene quantum dot conjugate as a novel and fluorescent theranostic tool for cancer.

BACKGROUND: Biosurfactants are amphipathic molecules of microbial origin that reduce surface and interfacial tension at gas-liquid-solid interfaces. Earlier, the biosurfactant was isolated and characterized in our laboratory from Candida parapsilosis. The property of the biosurfactant is further explored in this study by using quantum dots (QDs) as nanocarrier. MATERIALS AND METHODS: Graphene quantum dots (GQDs) were synthesized by bottom-up approach through pyrolysis of citric acid. GQDs were conjugated with both biosurfactant and folic acid (FA) using carbodiimide chemistry. The prepared GQD bioconjugate was studied for diagnostic and therapeutic effects against cancer cells. RESULTS AND DISCUSSION: Photoluminescence quantum yield (QY) of plain GQDs was measured as 12.8%. QY for biosurfactant conjugated GQDs and FA-biosurfactant conjugated GQDs was measured as 10.4% and 9.02%, respectively, and it was sufficient for targeting cancer cells. MTT assay showed that more than 90% of cells remained viable at concentration of 1 mg/mL, hence GQDs seemed to be non-toxic to cells. Biosurfactant conjugated GQDs caused 50% reduction in cellular viability within 24 hours. FA conjugation further increased the specificity of bioconjugated GQDs toward tumor cells, which is clearly evident from the drug internalization studies using confocal laser scanning microscopy. A higher amount of drug uptake was observed when bioconjugated GQDs were decorated with FA. CONCLUSION: The ability of GQD bioconjugate could be used as a theranostic tool for cancer. It is foreseen that in near future cancer can be detected and/or treated at an early stage by utilizing biosurfactant conjugated GQDs. Therefore, the proposed study would provide a stepping stone to improve the life of cancer patients.

Soil gas radon analysis in some areas of Northern Punjab, India.

The radon concentration levels in soil samples from 39 locations of Northern Punjab are measured using AlphaGUARD (PQ 2000 PRO Model) of Genitron instruments, Germany. The radon concentration in soil varies from 0.3 to 35.8 kBq/l. The minimum value of radon is observed in Talwandi Choudhrian and is maximum for Nushera Dhala. The soil gas radon is correlated with soil temperature, pressure, and humidity to observe the effect of these parameters on radon release. The soil gas radon values in the study area are compared with that obtained in groundwater. The results are also compared with the available radon data for other parts of Punjab and Himachal Pradesh.

Measurement of soil gas radon and its correlation with indoor radon around some areas of Upper Siwaliks, India.

Radon is a radioactive gas which makes the primary contribution to the natural radiation to which people are exposed. For that reason, great importance is attributed to the determination of radon concentration levels in water, indoor air and soil gas and outdoors. In this paper, measurements of radon concentration in soil gas have been carried out around some areas of the Upper Siwaliks of the Kala Amb, Nahan and Morni Hills, India, using a portable AlphaGUARD PQ 2000 device into which the soil gas is drawn using active pumping. The soil gas radon concentration around the Upper Siwaliks was found to vary from 11.5 +/- 0.9 to 78.47 +/- 3.1 kBq m(-3). The annual average indoor radon concentration in the study area was measured in the range from 71.7 +/- 21.0 to 421.7 +/- 33.6 Bq m( - 3) using LR-115 type II cellulose nitrate films in the bare mode. The values of soil gas radon concentration in the study area were compared with those from the adjoining low-radioactive areas of Punjab. Since the soil or bedrock beneath a building is one of the sources of radon gas in the indoor air, an effort has been made to find a possible correlation between soil gas radon with the indoor radon. A satisfactory positive correlation has been observed between soil gas radon and indoor radon in the study area.

Comparative study of natural radioactivity levels in soil samples from the Upper Siwaliks and Punjab, India using gamma-ray spectrometry.

Natural radioactive materials under certain conditions can reach hazardous radiological levels. So, it becomes necessary to study the natural radioactivity levels in soil to assess the dose for the population in order to know the health risks and to have a baseline for future changes in the environmental radioactivity due to human activities. The natural radionuclide (226Ra, 232Th, and 40K) contents in soil were determined for 26 locations around the Upper Siwaliks of Kala Amb, Nahan and Morni Hills, Northern India, using high-resolution gamma-ray spectrometric analysis. It was observed that the concentration of natural radionuclides viz., 226Ra, 232Th and 40K, in the soil varies from 28.3+/-0.5 to 81.0+/-1.7Bqkg(-1), 61.2+/-1.3 to 140.3+/-2.6Bqkg(-1) and 363.4+/-4.9 to 1002.2+/-11.2Bqkg(-1) respectively. The total absorbed dose rate calculated from activity concentration of 226Ra, 232Th and 40K ranged from 71.1 to 162.0nGyh(-1). The radium equivalent (Req) and the external hazard index (Hex), which resulted from the natural radionuclides in soil, were also calculated and found to vary from 149.4 to 351.8Bqkg(-1)and from 0.40 to 0.95 respectively. These values in Upper Siwaliks area were compared with that from the adjoining areas of Punjab. The radium equivalent activities in all the soil samples were lower than the limit (370Bqkg(-1)) set in the Organization for Economic Cooperation and Development (OECD) report and the dose equivalent was within the safe limit of 1mSvy(-1).

Estimation of uranium and radon concentration in some drinking water samples of Upper Siwaliks, India.

Uranium and radon concentration was assessed in water samples taken from hand pumps, natural sources and wells collected from some areas of Upper Siwaliks, Northern India. Fission track registration technique was used to estimate the uranium content of water samples. The uranium concentration in water samples was found to vary from 1.08 +/- 0.03 to 19.68 +/- 0.12 microg l(-1). These values were compared with safe limit values recommended for drinking water. Most of the water samples were found to have uranium concentration below the safe limit of 15 microg l(-1) (WHO, World Health Organization, Guidelines for drinking-water quality (3rd ed.). Geneva, Switzerland: WHO, 2004). The radon estimation in these water samples was made using alpha-scintillometry to study its correlation with uranium. The radon concentration in these samples was found to vary from 0.87 +/- 0.29 to 32.10 +/- 1.79 Bq l(-1). The recorded values of radon concentration were within the recommended safe limit of 4 to 40 Bq l(-1) (UNSCEAR, United Nations Scientific Committee on the Effects of Atomic Radiations, Sources and effects of ionizing radiation. New York: United Nations, 1993). No direct correlation was found between uranium concentration and radon concentration in water samples belonging to Upper Siwaliks. The values of uranium and radon concentration in water were compared with that from the adjoining areas of Punjab state, India.

Regional variations pattern of indoor radon levels in some areas of Punjab and Haryana.

The indoor radon concentration levels and their regional variations pattern, for two consecutive half-year periods, in a wide range of dwellings of some regions of Punjab and Haryana states have been studied. The objective was to find the relation between the variations of indoor radon levels with the sub-soil and local geology, type of building materials utilised in the dwellings of the region. Keeping this in view, indoor radon measurements have been carried out in the dwellings of 30 villages around the Tusham Ring Complex, Bhiwani district, Haryana, known to be composed of acidic volcanics and associated granites, along with 11 villages of Amritsar District, Punjab. The indoor radon concentration in the dwellings around Tusham (Haryana) was found to vary from 120 +/- 95 to 915 +/- 233 Bq m(-3), whereas radon levels varied from 60 +/- 37 to 235 +/- 96 Bq m(-3) for the dwellings studied in Punjab. We believe that local geology including embedded granitic rocks, and sub-soil, as well as building materials having higher radioactive content, is the major contributor for the higher indoor radon levels observed particularly in the dwelling around Tusham Ring complex, where some dwellings are showing higher radon concentrations than the ICRP recommendations. The environmental samples from some areas of Punjab state and around the Tusham Ring Complex of Haryana state have also been analysed for radon exhalation studies. Higher values for radon exhalation rates have been observed for the Tusham's soil/rock specimens, as compared with soil samples of the Amritsar region of Punjab.