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  1. Article ; Online: Culture-Independent Raman Spectroscopic Identification of Bacterial Pathogens from Clinical Samples Using Deep Transfer Learning.

    Singh, Saumya / Kumbhar, Dipak / Reghu, Dhanya / Venugopal, Shwetha J / Rekha, P T / Mohandas, Silpa / Rao, Shruti / Rangaiah, Ambica / Chunchanur, Sneha K / Saini, Deepak Kumar / Umapathy, Siva

    Analytical chemistry

    2022  Volume 94, Issue 42, Page(s) 14745–14754

    Abstract: The rapid identification of bacterial pathogens in clinical samples like blood, urine, pus, and sputum is the need of the hour. Conventional bacterial identification methods like culturing and nucleic acid-based amplification have limitations like poor ... ...

    Abstract The rapid identification of bacterial pathogens in clinical samples like blood, urine, pus, and sputum is the need of the hour. Conventional bacterial identification methods like culturing and nucleic acid-based amplification have limitations like poor sensitivity, high cost, slow turnaround time, etc. Raman spectroscopy, a label-free and noninvasive technique, has overcome these drawbacks by providing rapid biochemical signatures from a single bacterium. Raman spectroscopy combined with chemometric methods has been used effectively to identify pathogens. However, a robust approach is needed to utilize Raman features for accurate classification while dealing with complex data sets such as spectra obtained from clinical isolates, showing high sample-to-sample heterogeneity. In this study, we have used Raman spectroscopy-based identification of pathogens from clinical isolates using a deep transfer learning approach at the single-cell level resolution. We have used the data-augmentation method to increase the volume of spectra needed for deep-learning analysis. Our ResNet model could specifically extract the spectral features of eight different pathogenic bacterial species with a 99.99% classification accuracy. The robustness of our model was validated on a set of blinded data sets, a mix of cultured and noncultured bacterial isolates of various origins and types. Our proposed ResNet model efficiently identified the pathogens from the blinded data set with high accuracy, providing a robust and rapid bacterial identification platform for clinical microbiology.
    MeSH term(s) Spectrum Analysis, Raman/methods ; Bacteria ; Machine Learning ; Nucleic Acids ; Plant Extracts
    Chemical Substances Nucleic Acids ; Plant Extracts
    Language English
    Publishing date 2022-10-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.2c03391
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Engineering of a hybrid polymer-lipid nanocarrier for the nasal delivery of tenofovir disoproxil fumarate: physicochemical, molecular, microstructural, and stability evaluation.

    Pokharkar, Varsha B / Jolly, Mallika R / Kumbhar, Dipak D

    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

    2015  Volume 71, Page(s) 99–111

    Abstract: Purpose: To engineer a hybrid nanocarrier system based on lipid and polymer for the nasal delivery of tenofovir disoproxil fumarate (TDF), and further to investigate its physicochemical, molecular, microstructural, and stability aspects.: Methods: ... ...

    Abstract Purpose: To engineer a hybrid nanocarrier system based on lipid and polymer for the nasal delivery of tenofovir disoproxil fumarate (TDF), and further to investigate its physicochemical, molecular, microstructural, and stability aspects.
    Methods: Nanoparticles were prepared by melt emulsification-probe sonication technique. A 3(2) factorial design was used to identify key formulation variables influencing the characteristics of drug-loaded carrier. FT-IR, mass spectroscopy (MS) and (1)H NMR was used to probe molecular interactions among the components of the system, while the surface morphology was imagined through electron microscopy (TEM and SEM). Thermal analysis and powder X-ray diffraction (PXRD) was used to explore melting and crystallization behavior of drug and the carrier lipid. PLN-9 GEL was studied for its rheology, drug release, ex-vivo permeation, histopathology, and stability.
    Results: Batch PLN-9 had size of 239 nm, drug encapsulation of 87.14% and revealed spherical morphology. MS, FT-IR and (1)H NMR established compatibility between the drug (TDF) and the carrier lipid (Lauric acid), while, a strong H-bonding was identified between the amino (-NH2) group of drug and the carboxyl (-COOH) group of pemulen polymer. Thermal analysis confirmed an amorphous TDF within the carrier matrix. PXRD analysis indicated substantial change in the molecular packing and subcell structure of carrier lipid during the PLN processing. PLN-9 GEL had shear thinning rheology, an anomalous type (n>0.5) of drug release and possessed potential to transport TDF across the nasal mucosa with an average flux of 135.36 μg/cm(2)/h.
    Conclusion: The designed carrier can encapsulate TDF and accentuates its transnasal flux, thus could be used as a carrier for an effective nasal delivery of TDF.
    MeSH term(s) Administration, Intranasal ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/chemistry ; Calorimetry, Differential Scanning ; Drug Carriers/administration & dosage ; Drug Carriers/chemistry ; Drug Liberation ; Drug Stability ; Lipids/chemistry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Nasal Mucosa/anatomy & histology ; Nasal Mucosa/drug effects ; Nasal Mucosa/metabolism ; Polymers/chemistry ; Powder Diffraction ; Reverse Transcriptase Inhibitors/administration & dosage ; Reverse Transcriptase Inhibitors/chemistry ; Rheology ; Spectroscopy, Fourier Transform Infrared ; Tenofovir/administration & dosage ; Tenofovir/chemistry ; X-Ray Diffraction
    Chemical Substances Anti-HIV Agents ; Drug Carriers ; Lipids ; Polymers ; Reverse Transcriptase Inhibitors ; Tenofovir (99YXE507IL)
    Language English
    Publishing date 2015-04-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1154366-8
    ISSN 1879-0720 ; 0928-0987
    ISSN (online) 1879-0720
    ISSN 0928-0987
    DOI 10.1016/j.ejps.2015.02.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ultrasound-Assisted Facile Synthesis of Nanostructured Hybrid Vesicle for the Nasal Delivery of Indomethacin: Response Surface Optimization, Microstructure, and Stability.

    Patil, Suraj S / Kumbhar, Dipak D / Manwar, Jagdish V / Jadhao, Rajesh G / Bakal, Ravindra L / Wakode, Sharad

    AAPS PharmSciTech

    2019  Volume 20, Issue 3, Page(s) 97

    Abstract: This work is devoted to design a novel nanostructured hybrid vesicle (NHV) made of lecithin and an acrylate/C10-C30 alkyl acrylate for the nasal delivery of a model active indomethacin (IND), and further to probe its microstructure, intermolecular ... ...

    Abstract This work is devoted to design a novel nanostructured hybrid vesicle (NHV) made of lecithin and an acrylate/C10-C30 alkyl acrylate for the nasal delivery of a model active indomethacin (IND), and further to probe its microstructure, intermolecular interactions, drug release behavior, ex vivo permeation, and stability. NHVs were prepared by cavitation technology employing RSM-based central composite design (CCD). Amount of lecithin (X
    MeSH term(s) Administration, Intranasal ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/chemistry ; Indomethacin/administration & dosage ; Indomethacin/chemistry ; Lecithins/analysis ; Microscopy, Electron, Transmission ; Nasal Mucosa/metabolism ; Particle Size ; Permeability ; Sheep ; Spectroscopy, Fourier Transform Infrared ; Surface Properties
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Lecithins ; Indomethacin (XXE1CET956)
    Language English
    Publishing date 2019-01-29
    Publishing country United States
    Document type Journal Article
    ISSN 1530-9932
    ISSN (online) 1530-9932
    DOI 10.1208/s12249-018-1247-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Physicochemical investigations on an engineered lipid–polymer hybrid nanoparticle containing a model hydrophilic active, zidovudine

    Kumbhar, Dipak D / Pokharkar, Varsha B

    Colloids and surfaces. 2013 Sept. 5, v. 436

    2013  

    Abstract: The objective of this work was to develop an optimized lipid–polymer hybrid nanoparticle (LPN) for zidovudine (AZT), a model hydrophilic active, and further to investigate its crystallization behavior and possible molecular interactions with the carrier ... ...

    Abstract The objective of this work was to develop an optimized lipid–polymer hybrid nanoparticle (LPN) for zidovudine (AZT), a model hydrophilic active, and further to investigate its crystallization behavior and possible molecular interactions with the carrier during the LPN processing. AZT-LPNs were prepared by melt emulsification-probe sonication technique using a 2³ factorial design. Transmission electron microscopy (TEM) revealed spherical LPNs with two distinct boundaries representing the drug loaded lipid core surrounded by a polymer. The optimized batch (LPN-2) achieved a size of 175±2.5nm, drug encapsulation of 49.26±0.75%, and revealed a significant stability for six months. Molecular interactions among the component of LPN were studied by using proton nuclear magnetic resonance (¹H NMR), and Fourier transform infrared spectra (FT-IR). The complete amorphization of drug was noted in the melt sample while LPN-2 showed a partial drug recystallization. This was confirmed by the thermal analysis and diffractometry studies. The presence of pemulen polymer was significant to restrict sonication assisted recrystallization of the active. The oscillatory measurement using stress sweep and frequency sweep demonstrated elastic nature of the LPN-2, and was subsequently confirmed through the phase angle (δ°). Fickian diffusion (n<0.5) was identified as drug release mechanism from LPN-2. The partial hydrophilic nature of lipid and the presence of amphiphilic surfactant (Acconon® CO-7) influenced AZT release from LPN. Finally, based on the understanding of molecular interactions, the LPNs made of polar lipid (Cutina® HR) and hydrophobically modified polymer (Pemulen TR-2®) hold the promise to entrap model hydrophilic active, zidovudine, and it is possible to optimize drug release to desired level.
    Keywords Fourier transform infrared spectroscopy ; colloids ; crystallization ; drugs ; encapsulation ; hydrophilicity ; melting ; nanoparticles ; nuclear magnetic resonance spectroscopy ; polymers ; surfactants ; thermal analysis ; transmission electron microscopy
    Language English
    Dates of publication 2013-0905
    Size p. 714-725.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500517-3
    ISSN 0927-7757
    ISSN 0927-7757
    DOI 10.1016/j.colsurfa.2013.07.044
    Database NAL-Catalogue (AGRICOLA)

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  5. Article: Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: Physicochemical investigations

    Kumbhar, Dipak D / Pokharkar, Varsha B

    Colloids and surfaces. 2013 Jan. 5, v. 416

    2013  

    Abstract: The purpose of this study was to develop an optimized nanostructured lipid carrier (NLC) for bicalutamide (BCT), a poorly water-soluble drug, and to investigate its phase transition behavior during the NLC processing. BCT loaded NLCs (BCT-NLCs) were ... ...

    Abstract The purpose of this study was to develop an optimized nanostructured lipid carrier (NLC) for bicalutamide (BCT), a poorly water-soluble drug, and to investigate its phase transition behavior during the NLC processing. BCT loaded NLCs (BCT-NLCs) were prepared using a hot high-pressure homogenization (HPH) technique. Factorial design (2³) was used to identify the key formulation variables influencing particle size, percent drug encapsulation, and zeta potential of the NLC. The optimized batch (NLC-2) revealed spherical morphology with a smooth surface under scanning electron microscopy (SEM). NLC-2 achieved a high drug encapsulation of 98.48±0.70% and demonstrated good stability for six months. Drug–lipid interaction was investigated using Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance (¹H NMR). BCT phase transition occurred during the NLC processing and BCT crystalline Form I was identified in NLC-2. The same was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Raman analysis. The in vitro release study of NLC-2, revealed peppas release kinetics with Fickian diffusion (n<0.5) as drug release mechanism. The presence of hydrophilic surfactants was significant to modulate BCT release from NLC-2. Finally, NLCs made of Precirol® ATO 5 (solid lipid) and triacetin (oil) posses the potential to entrap the poorly water-soluble drug, bicalutamide and the system can be tailor-made to meet the desired drug release. This may provide better prospects for the oral delivery of bicalutamide.
    Keywords Fourier transform infrared spectroscopy ; X-ray diffraction ; colloids ; differential scanning calorimetry ; drugs ; encapsulation ; homogenization ; hydrophilicity ; nuclear magnetic resonance spectroscopy ; oils ; particle size ; phase transition ; scanning electron microscopy ; surfactants ; triacetin ; zeta potential
    Language English
    Dates of publication 2013-0105
    Size p. 32-42.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500517-3
    ISSN 0927-7757
    ISSN 0927-7757
    DOI 10.1016/j.colsurfa.2012.10.031
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: Physicochemical investigations

    Kumbhar, Dipak D. / Pokharkar, Varsha B.

    Colloids and surfaces

    Volume v. 416

    Abstract: The purpose of this study was to develop an optimized nanostructured lipid carrier (NLC) for bicalutamide (BCT), a poorly water-soluble drug, and to investigate its phase transition behavior during the NLC processing. BCT loaded NLCs (BCT-NLCs) were ... ...

    Abstract The purpose of this study was to develop an optimized nanostructured lipid carrier (NLC) for bicalutamide (BCT), a poorly water-soluble drug, and to investigate its phase transition behavior during the NLC processing. BCT loaded NLCs (BCT-NLCs) were prepared using a hot high-pressure homogenization (HPH) technique. Factorial design (2³) was used to identify the key formulation variables influencing particle size, percent drug encapsulation, and zeta potential of the NLC. The optimized batch (NLC-2) revealed spherical morphology with a smooth surface under scanning electron microscopy (SEM). NLC-2 achieved a high drug encapsulation of 98.48±0.70% and demonstrated good stability for six months. Drug–lipid interaction was investigated using Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance (¹H NMR). BCT phase transition occurred during the NLC processing and BCT crystalline Form I was identified in NLC-2. The same was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Raman analysis. The in vitro release study of NLC-2, revealed peppas release kinetics with Fickian diffusion (n<0.5) as drug release mechanism. The presence of hydrophilic surfactants was significant to modulate BCT release from NLC-2. Finally, NLCs made of Precirol® ATO 5 (solid lipid) and triacetin (oil) posses the potential to entrap the poorly water-soluble drug, bicalutamide and the system can be tailor-made to meet the desired drug release. This may provide better prospects for the oral delivery of bicalutamide.
    Keywords zeta potential ; particle size ; drugs ; homogenization ; oils ; X-ray diffraction ; colloids ; hydrophilicity ; triacetin ; surfactants ; phase transition ; differential scanning calorimetry ; scanning electron microscopy ; nuclear magnetic resonance spectroscopy ; Fourier transform infrared spectroscopy ; encapsulation
    Language English
    Document type Article
    ISSN 0927-7757
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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  7. Article: Physicochemical investigations on an engineered lipid–polymer hybrid nanoparticle containing a model hydrophilic active, zidovudine

    Kumbhar, Dipak D. / Pokharkar, Varsha B.

    Colloids and surfaces

    Volume v. 436

    Abstract: The objective of this work was to develop an optimized lipid–polymer hybrid nanoparticle (LPN) for zidovudine (AZT), a model hydrophilic active, and further to investigate its crystallization behavior and possible molecular interactions with the carrier ... ...

    Abstract The objective of this work was to develop an optimized lipid–polymer hybrid nanoparticle (LPN) for zidovudine (AZT), a model hydrophilic active, and further to investigate its crystallization behavior and possible molecular interactions with the carrier during the LPN processing. AZT-LPNs were prepared by melt emulsification-probe sonication technique using a 2³ factorial design. Transmission electron microscopy (TEM) revealed spherical LPNs with two distinct boundaries representing the drug loaded lipid core surrounded by a polymer. The optimized batch (LPN-2) achieved a size of 175±2.5nm, drug encapsulation of 49.26±0.75%, and revealed a significant stability for six months. Molecular interactions among the component of LPN were studied by using proton nuclear magnetic resonance (¹H NMR), and Fourier transform infrared spectra (FT-IR). The complete amorphization of drug was noted in the melt sample while LPN-2 showed a partial drug recystallization. This was confirmed by the thermal analysis and diffractometry studies. The presence of pemulen polymer was significant to restrict sonication assisted recrystallization of the active. The oscillatory measurement using stress sweep and frequency sweep demonstrated elastic nature of the LPN-2, and was subsequently confirmed through the phase angle (δ°). Fickian diffusion (n<0.5) was identified as drug release mechanism from LPN-2. The partial hydrophilic nature of lipid and the presence of amphiphilic surfactant (Acconon® CO-7) influenced AZT release from LPN. Finally, based on the understanding of molecular interactions, the LPNs made of polar lipid (Cutina® HR) and hydrophobically modified polymer (Pemulen TR-2®) hold the promise to entrap model hydrophilic active, zidovudine, and it is possible to optimize drug release to desired level.
    Keywords transmission electron microscopy ; drugs ; colloids ; thermal analysis ; hydrophilicity ; melting ; surfactants ; crystallization ; nanoparticles ; polymers ; nuclear magnetic resonance spectroscopy ; Fourier transform infrared spectroscopy ; encapsulation
    Language English
    Document type Article
    ISSN 0927-7757
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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