Browsing by Author "Shyam Lal Mudavath"

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Carboxymethyl chitosan modified lipid nanoformulations as a highly efficacious and biocompatible oral anti-leishmanial drug carrier system
(Elsevier B.V., 2022) Aakriti Singh; Ganesh Yadagiri; Manorma Negi; Anurag Kumar Kushwaha; Om Prakash Singh; Shyam Sundar; Shyam Lal Mudavath
Herein, carboxymethyl chitosan (CMC) grafted lipid nanoformulations were facilely prepared by thin-film hydration method as a highly efficient biocompatible anti-leishmanial carrier encapsulating amphotericin B (AmB). Nanoformulations were characterized for their physicochemical characteristics wherein TEM analysis confirmed the spherical structure, whereas FTIR analysis revealed the conjugation of CMC onto nanoformulations and confirmed the free state of AmB. Furthermore, the wettability study confirmed the presence of CMC on the surface of nanoformulations attributed to the enhanced hydrophilicity. Surface hydrophilicity additionally contributes towards consistent mucin retention ability for up to 6 h, superior mucoadhesiveness, and hence enhanced bioavailability. The proposed nanoformulations with high encapsulation and drug loading properties displayed controlled drug release in the physiological microenvironment. In vitro, antileishmanial results showed an astounding 97% inhibition in amastigote growth. Additionally, in vivo studies showed that treatment with nanoformulations significantly reduced the liver parasitic burden (93.5%) without causing any toxicity when given orally. © 2022 Elsevier B.V.
Characterization and evaluation of amine-modified graphene amphotericin B for the treatment of visceral leishmaniasis: In vivo and in vitro studies
(Dove Medical Press Ltd., 2014) Shyam Lal Mudavath; Mahe Talat; Madhukar Rai; Onkar Nath Srivastava; Shyam Sundar
Amphotericin B (AmB) has been the first-line treatment for visceral leishmaniasis (VL), a neglected protozoan disease, especially in regions like Bihar, India, where resistance to antimonials is widespread. However, adverse drug reactions are a major limiting factor. We evaluated a novel formulation of AmB conjugated to amine-modified graphene (f-Gr) for safety and efficacy over conventional AmB. The f-Gr was prepared in a gentle one-step process of noncovalent (amine) functionalization with the help of amino acid L-cysteine. This f-Gr was further conjugated to AmB by peptide bond. The conjugate (f-Gr-AmB) was characterized by Raman spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. f-Gr-AmB was found to exhibit lesser cytotoxicity toward J774A.1 cells than AmB, and did not induce any hepatic or renal toxicity in Swiss albino mice. In vitro antileishmanial assay in J774A.1 cells showed significantly enhanced efficacy of f-Gr-AmB over AmB. Furthermore, percentage inhibition of amastigote replication in a hamster model of VL was significantly higher in the f-Gr-AmB treated group (87.8%) compared to the AmB group (70.4%). These results suggest that f-Gr-AmB could be a safe and effective alternative to conventional AmB in the treatment of VL. © 2014 Mudavath et al.
Coalition of Biological Agent (Melatonin) with Chemotherapeutic Agent (Amphotericin B) for Combating Visceral Leishmaniasis via Oral Administration of Modified Solid Lipid Nanoparticles
(American Chemical Society, 2023) Shabi Parvez; Ganesh Yadagiri; Kanika Arora; Aaqib Javaid; Anurag Kumar Kushwaha; Om Prakash Singh; Shyam Sundar; Shyam Lal Mudavath
In this study, 2-hydroxypropyl-β-cyclodextrin (HPβCD) grafted solid lipid nanoparticle (SLN)-based bioconjugate was synthesized and used for administering a combination of melatonin (Mel) and amphotericin B (AmB) orally for effective visceral leishmaniasis (VL) treatment. The formulations (HPCD-Mel-AmB SLN) were synthesized by the emulsion solvent evaporation method. HPCD-Mel-AmB SLN showed a high loading capacity and a high entrapment efficiency of AmB (% DL = 9.0 ± 0.55 and % EE = 87.9 ± 0.57) and Mel (% DL = 7.5 ± 0.51 and % EE = 63 ± 6.24). The cumulative percent release of AmB and Mel was 66.10 and 73.06%, respectively, up to 72 h. Time-dependent cellular uptake was noticed for HPCD-Mel-AmB SLN for 4 h. Further, HPCD-Mel-AmB SLN did not show any toxic effects on J774A.1 macrophages and Swiss albino mice. HPCD-Mel-AmB SLN (10 mg/kg ×5 days, p.o.) has significantly diminished (98.89%) the intracellular parasite load in liver tissues of L. donovani-infected BALB/c mice, subsequently highlighting the role of melatonin toward an effective strategy in combating leishmanial infection. Therefore, these results indicated that administration of HPCD-Mel-AmB SLN improve the therapeutic index of the first-line drug in addition to the introduction of biological agent and would be a promising therapeutic candidate for effective VL therapy. In the present study, the objective is to test the efficacy of the chemotherapeutic approach in combination with a biological immunomodulatory agent against leishmanial infection using in vitro and in vivo studies. This information suggests that melatonin could be an efficacious and potent antileishmanial agent. © 2023 American Chemical Society. All rights reserved.
Comparative evaluation of blood and serum samples in rapid Immunochromatographic tests for visceral Leishmaniasis
(2013) Dinesh Kumar; Basudha Khanal; Puja Tiwary; Shyam Lal Mudavath; Narendra K. Tiwary; Rupa Singh; Kanika Koirala; Marleen Boelaert; Suman Rijal; Shyam Sundar
Rapid diagnostic tests (RDTs) based on the detection of specific antibodies in serum are commonly used for the diagnosis of visceral leishmaniasis (VL). Several commercial kits are available, and some of them allow the use of whole-blood samples instead of serum. An RDT is much more user-friendly for blood samples than for serum samples. In this study, we examined the sensitivities and specificities of six different commercially available immunochromatographic tests for their accuracy in detecting Leishmania infection in whole blood and serum of parasitologically confirmed VL cases. This study was performed in areas of India and Nepal where VL is endemic. A total of 177 confirmed VL cases, 208 healthy controls from areas of endemicity (EHCs), 26 malaria patients (MP), and 37 tuberculosis (TB) patients were enrolled. The reproducibilities of the blood and serum results and between-reader and between-laboratory results were tested. In India, the sensitivities of all the RDTs ranged between 94.7 and 100.0%, with no significant differences between whole blood and serum. The specificities ranged between 92.4 and 100.0%, except for the specificity of the Onsite Leishmania Ab RevB kit, which was lower (33.6 to 42.0%). No differences in specificities were observed for blood and serum. In Nepal, the sensitivities of all the test kits, for whole-blood as well as serum samples, ranged between 96.3 and 100.0%, and the specificities ranged between 90.1 and 96.1%, again with the exception of that of the Onsite Leishmania Ab RevB test, which was markedly lower (48.7 to 49.3%). The diagnostic accuracies of all the tests, except for one brand, were excellent for the whole-blood and serum samples. We conclude that whole blood is an adequate alternative for serum in RDTs for VL, with sensitivities and specificities comparable to those obtained in serum samples, provided that the test kit is of overall good quality.Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Dual Drug Delivery for Augmenting Bacterial Wound Complications via Tailored Ultradeformable Carriers
(American Chemical Society, 2024) Kanika Arora; Bharti Dhruw; Sherilraj Pm; Prasoon Madhukar; Shyam Sundar; Shyam Lal Mudavath
Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of −36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 μg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 μg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries. © 2024 American Chemical Society.
Envisioning the innovations in nanomedicine to combat visceral leishmaniasis: For future theranostic application
(Future Medicine Ltd., 2019) Om Prakash Singh; Mallikarjuna Rao Gedda; Shyam Lal Mudavath; Onkar Nath Srivastava; Shyam Sundar
Visceral leishmaniasis (VL) is a life-threatening parasitic disease affecting impoverished people of the developing world; and much effort has been spent on the early case detection and treatment. However, current diagnostics and treatment options are not sufficient for appropriate surveillance in VL elimination setting. Hence, there is a dire need to develop highly sensitive diagnostics and less toxic effective treatments for proper management of cases and to achieve the sustained disease elimination. Although, promising results have been observed with nanomedicines in leishmaniasis; there are great challenges ahead especially in translating this to clinical setting. This review provides updated progress of nanomedicines in VL, and discussed how these innovations and future directions play vital role in achieving VL elimination. © 2019 Future Medicine Ltd.
Evaluation of Safety and Antileishmanial Efficacy of Amine Functionalized Carbon-Based Composite Nanoparticle Appended With Amphotericin B: An in vitro and Preclinical Study
(Frontiers Media S.A., 2020) Mallikarjuna Rao Gedda; Prasoon Madhukar; Alok Kumar Vishwakarma; Vimal Verma; Anurag Kumar Kushwaha; Ganesh Yadagiri; Shyam Lal Mudavath; Om Prakash Singh; Onkar Nath Srivastava; Shyam Sundar
Visceral leishmaniasis (VL) has been a major health concern in the developing world, primarily affecting impoverished people. It is caused by a protozoan parasite Leishmania donovani and is characterized by immune dysfunction that can lead to deadly secondary infections. Several adverse side effects limit the existing treatment options; hence, the need of the hour is some drug option with high efficacy and no toxicity. To make targeted delivery of Amphotericin B (AmB), we have used amine-functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene (f-Grap). The results with f-Grap-AmB, because of a much larger surface area, were expected to be better. However, the results obtained by us showed only marginal improvement (IC50 f-Grap-AmB; 0.0038 ± 0.00119 μg/mL). This is, in all likelihood, due to the agglomeration effect of f-Grap-AmB, which is invariably obtained with graphene. To resolve this issue, we have synthesized a graphene-CNT composite (graphene 70% and CNT 30% by weight). Because CNT is dispersed in between graphene sheets, the agglomeration effect is avoided, and our study suggests that the f-Composite-AmB (f-Comp-AmB) showed no toxicity against the murine J774A.1 macrophage cell line and did not induce any hepatic or renal toxicity in Swiss albino mice. The f-Comp-AmB also showed a remarkable elevation in the in vitro and in vivo antileishmanial efficacy in comparison to AmB and f-CNT-AmB or f-Grap-AmB in J774A.1 and Golden Syrian hamsters, respectively. Additionally, we have also observed that the percentage suppression of parasite replication in the spleen of the hamster was significantly higher in the f-Comp-AmB (97.79 ± 0.2375) treated group in comparison with the AmB (85.66 ± 1.164) treated group of hamsters. To conclude, f-Comp-AmB could be a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventional AmB. © Copyright © 2020 Gedda, Madhukar, Vishwakarma, Verma, Kushwaha, Yadagiri, Mudavath, Singh, Srivastava and Sundar.
Formulation, characterization and in vitro anti-leishmanial evaluation of amphotericin B loaded solid lipid nanoparticles coated with vitamin B12-stearic acid conjugate
(Elsevier Ltd, 2020) Aakriti Singh; Ganesh Yadagiri; Shabi Parvez; Om Prakash Singh; Anurag Verma; Shyam Sundar; Shyam Lal Mudavath
Despite the advancement of new anti-leishmanials, amphotericin B (AmB) prevails as one of the most potent agent in the treatment of visceral leishmaniasis (VL), a neglected tropical disease affecting mostly poverty ridden and underdeveloped regions of the globe. Nonetheless, many patients display intolerance to parenteral AmB, notably at higher dosages. Also, conventional AmB presents an apparently poor absorption. Therefore, to improve AmB bioavailability and overcome multiple barriers for oral delivery of AmB, we fabricated a promising vitamin B12-stearic acid (VBS) conjugate coated solid lipid nanoparticles (SLNs) encapsulated with AmB (VBS-AmB-SLNs) by a combination of double emulsion solvent evaporation and thermal sensitive hydrogel techniques. VBS-AmB-SLNs showed a particle size of 306.66 ± 3.35 nm with polydispersity index of 0.335 ± 0.08 while the encapsulation efficiency and drug loading was observed to be 97.99 ± 1.6% and 38.5 ± 5.6% respectively. In vitro drug release showed a biphasic release pattern and chemical stability of AmB was ensured against simulated gastrointestinal fluids. Cellular uptake studies confirmed complete internalization of the formulation. Anti-leishmanial evaluation against intramacrophage amastigotes showed an enhanced efficacy of 94% which was significantly (P < 0.01) higher than conventional AmB without showing any toxic effects on J774A.1 cells. VBS-AmB-SLNs could serve as a potential therapeutic strategy against VL. © 2020 Elsevier B.V.
Hijacking the intrinsic vitamin B12 pathway for the oral delivery of nanoparticles, resulting in enhanced in vivo anti-leishmanial activity
(Royal Society of Chemistry, 2022) Aakriti Singh; Ganesh Yadagiri; Aaqib Javaid; Krishna Kumar Sharma; Anurag Verma; Om Prakash Singh; Shyam Sundar; Shyam Lal Mudavath
Surface-functionalized vitamin B12 (VB12) biocompatible nanoparticles exploit the well-characterized uptake pathway of VB12, shielding it from enzymatic degradation and inadequate absorption. In this perspective, subsequent to escalated mucus interaction and diffusion analysis, the nanoparticles were investigated by immunostaining with the anti-CD320 antibody, and their internalization mechanisms were examined by selectively blocking specific uptake processes. It was observed that their internalization occurred via an energy-dependent clathrin-mediated mechanism, simultaneously highlighting their remarkable ability to bypass the P-glycoprotein efflux. In particular, the synthesized nanoparticles were evaluated for their cytocompatibility by analyzing cellular proliferation, membrane viscoelasticity, and fluidity by fluorescence recovery after photobleaching and oxidative-stress detection, making them well-suited for successful translation to a clinical setup. Our previous in vitro antileishmanial results were paramount for their further in vivo and toxicity analysis, demonstrating their targeted therapeutic efficiency. The augmented surface hydrophilicity, which is attributed to VB12, and monomerization of amphotericin B in the lipid core strengthened the oral bioavailability and stability of the nanoparticles, as evidenced by the fluorescence resonance energy transfer analysis. © 2022 The Royal Society of Chemistry.
Impact of Dual‑coated Silver Nanoparticle and Antibiotic Sutures on Wound Healing in Inflammatory Mouse Models
(Wolters Kluwer Medknow Publications, 2024) Vaibhav Pandey; Amit Gupta; Indra Singh Choudhary; Mohammad Imran; Shyam Lal Mudavath; Amrita Ghosh Kar; Ruchira Nandan
Background: The use of silver nanoparticles (AgNPs) in biomedicine has emerged in a big way owing to its antibacterial and anti‑inflammatory properties. We hypothesize that combining the AgNPs with antibiotics for coating sutures will enhance the antibacterial property of sutures with the added advantage of the immunomodulatory effect of AgNPs on tissue healing. Materials and Methods: Polyglactin sutures were coated with AgNPs using the dip‑coating method. The uniform coating and morphology of AgNPs on the suture surface were confirmed using scanning electron microscopy (SEM). Each type of suture – polyglactin plain, antibiotic coated (Triclosan), AgNP coated, and dually coated (antibiotic and AgNP) – was assessed for their antibacterial properties against Gram‑positive bacteria, Gram‑negative bacteria, and anaerobes. These sutures were utilized in an abdominal and systemic inflammatory mice model for ileal anastomosis. The intestinal tissue was evaluated for acute and chronic inflammation and collagen deposition to assess the healing and inflammatory response. Results: The SEM and energy dispersive X‑ray analysis showed successful coating of AgNPs on plain and antibiotic‑coated sutures. In comparison with the other groups, the dually coated suture had the best in vitro antibacterial efficacy. The AgNP‑coated sutures were able to decrease both acute and chronic inflammatory cell infiltration, but the collagen synthesis and deposition were enhanced. Conclusion: AgNPs can be coated on Polyglactin suture either alone or in combination with antibiotics with preserved antibacterial effects. The dual coating of sutures gives a synergistic antibacterial effect. The AgNP diminishes immune response in the presence of preserved extracellular matrix generation. © 2024 Journal of Indian Association of Pediatric Surgeons.
Improvising anti-leishmanial activity of amphotericin B and paromomycin using co-delivery in D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) tailored nano-lipid carrier system
(Elsevier Ireland Ltd, 2020) Shabi Parvez; Ganesh Yadagiri; Aakriti Singh; Archana Karole; Om Prakash Singh; Shyam Sundar; Shyam Lal Mudavath
In the current study, we have focused on the design, development and in-vitro evaluation of D-α-tocopheryl polyethylene glycol 1000 succinate modified amphotericin B (AmB) and paromomycin (PM) loaded solid lipid nanoparticles (TPGS-SLNPs) by emulsion-solvent evaporation method. The optimized TPGS-SLNPs had a mean particle size of 199.4 ± 18.9 nm with a polydispersity index of 0.22 ± 0.14 and entrapment efficiency for AmB and PM was found to be 94 ± 1.5 % and 89 ± 0.50 % respectively. The prepared lipid nanoparticles were characterized by Powdered X-ray diffraction study, Fourier transform infrared spectroscopy, Nuclear magnetic resonance spectroscopy to confirm the absence of any interaction between lipids and drugs. The developed formulation showed a sustained drug release over a period of 48 h and were stable at different temperatures. Finally, TPGS-SLNPs (1 μg/mL) was found to significantly (P < 0.001) mitigate the intra-cellular amastigote growth compared to free AmB. The results obtained suggest TPGS-SLNPs could be an efficient carrier for delivering poorly water-soluble drugs and efficiently enhance its therapeutic potential. © 2020 Elsevier B.V.
In vivo assessment of antileishmanial property of 4-(4,4,8-trimethyl-7-oxo- 3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester, an oxabicyclo[ 3.3.1]nonanones
(Bentham Science Publishers B.V., 2014) Prakash Saudagar; Shyam Lal Mudavath; Pipas Saha; Anil K. Saikia; Shyam Sundar; Vikash Kumar Dubey
The high toxicity and the growing resistance are the major drawbacks of available antileishmanials. Our previous in vitro studies have identified oxabicyclo[3.3.1]nonanones as antileishmanial agents that act on the redox enzymes of the parasite. In the current study, antileishmanial activity of 4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester (PS 203) the most potent oxabicyclo[3.3.1]nonanone identified in our previous study is evaluated using the hamster model. There was 77.29 ± 3.0 % inhibition of parasite growth observed after a 5-day treatment of 5 mg/kg body weight dose. Further, the in vivo toxicity study of the compound in Swiss albino mice revealed no hepatic or renal toxicity. © 2014 Bentham Science Publishers.
Leishmania Proteomics: Insight into Diagnostics and Vaccine Development
(Springer Nature, 2024) Dharmendra Kumar Maurya; Shyamali; Shyam Lal Mudavath; Shyam Sundar; Om Prakash Singh
Visceral leishmaniasis (VL), a life-threatening parasitic disease in the Indian subcontinent, is caused by the protozoan parasites-Leishmania donovani and transmitted by the bite of the Phlebotomus sand fly. These parasites have adopted many invasion mechanisms to survive the host’s direct immune responses and established themselves in the host cells. Although efforts have been made to develop sensitive biomarkers for diagnosis and effective vaccines for VL treat-ment, we still need to achieve these goals with great success. Advances in various proteomic platforms have allowed us to identify large numbers of surface and cytosolic proteins from mixed stages of the Leishmania life cycle, which can be manipulated as a diagnostic marker or can be used as vaccine candidates. In this review, we highlight the proteins in amastigote and promastigote forms of Leish-mania parasite and discuss their potential implications in future diagnostic and vaccine development. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
Mannose-conjugated curcumin-chitosan nanoparticles: Efficacy and toxicity assessments against Leishmania donovani
(Elsevier B.V., 2018) Pramila Chaubey; Brahmeshwar Mishra; Shyam Lal Mudavath; Ravi R. Patel; Sundeep Chaurasia; Shyam Sundar; Vasanti Suvarna; Marvis Monteiro
Aim was to fabricate and optimize CUR-loaded mannose-functionalized chitosan nanoparticles (Cur-MCN) which overcome the limitations of drugs to reach the intracellular locations and to establish its therapeutic potential in visceral leishmaniasis by targeting of CUR to macrophages. Cur-MCN were developed by mannose-conjugated chitosan and have been tested for their efficacy and toxicit. In vivo antileishmanial activity in hamsters has shown significantly greater suppression of parasite replication in the spleen with Cur-MCN than unconjugated chitosan nanoparticles. The in vitro cytotoxicity study against the J774A.1 cell line demonstrated its comparative non-toxicity towards the macrophage cells. The potential of Cur-MCN was also confirmed by minimal observed cytotoxicity in our in vivo studies. © 2018 Elsevier B.V.
Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis
(Nature Research, 2020) Shabi Parvez; Ganesh Yadagiri; Mallikarjuna Rao Gedda; Aakriti Singh; Om Prakash Singh; Anurag Verma; Shyam Sundar; Shyam Lal Mudavath
The development of an effective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-β-cyclodextrin (HPCD) modified solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modified dual drug-loaded solid lipid nanoparticles (m-DDSLNs). The optimized formulations have a mean particle size of 141 ± 3.2 nm, a polydispersity index of 0.248 ± 0.11 and entrapment efficiency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confirmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profile upto 57% (AmB) and 21.5% (PM) within 72 h and were stable at both 4 °C and 25 °C during short term stability studies performed for 2 months. Confocal laser scanning microscopy confirmed complete cellular internalization of SLNs within 24 h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confirmed the safety and biocompatibility of the developed formulations. Further, m-DDSLNs did not induce any hepatic/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fluids and simulated intestinal fluids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1 µg/ml) has shown a maximum percentage of inhibition (96.22%) on intra-cellular amastigote growth of L. donovani. m-DDSLNs (20 mg/kg × 5 days, p.o.) has significantly (P < 0.01) reduced the liver parasite burden as compared to miltefosine (3 mg/kg × 5 days, p.o.) in L. donovani-infected BALB/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a promising approach towards the oral delivery of anti-leishmanial drugs. © 2020, The Author(s).
Nanodiagnostics in leishmaniasis: A new frontiers for early elimination
(Wiley-Blackwell, 2021) Mallikarjuna Rao Gedda; Prasoon Madhukar; Ashish Shukla; Shyam Lal Mudavath; Onkar Nath Srivastava; Om Prakash Singh; Shyam Sundar
Visceral leishmaniasis (VL) is still a major public health concern in developing countries having the highest outbreak and mortality potential. While the treatment of VL has greatly improved in recent times, the current diagnostic tools are limited for use in the post-elimination setting. Although conventional serological methods of detection are rapid, they can only differentiate between active disease in strict combination with clinical criteria, and thus are not sufficient enough to diagnose relapse patients. Therefore, there is a dire need for a portable, authentic, and reliable assay that does not require large space, specialized instrument facilities, or highly trained laboratory personnel and can be carried out in primary health care settings. Advances in the nanodiagnostic approaches have led to the expansion of new frontiers in the concerned area. The nanosized particles are blessed with an ability to interact one-on-one with the biomolecules because of their unique optical and physicochemical properties and high surface area to volume ratio. Biomolecular detection systems based on nanoparticles (NPs) are cost-effective, rapid, nongel, non-PCR, and nonculture based that provide fast, one-step, and reliable results with acceptable sensitivity and specificity. In this review, we discuss different NPs that are being used for the identification of molecular markers and other biomarkers, such as toxins and antigens associated with leishmaniasis. The most promising diagnostic approaches have been included in the article, and the ability of biomolecular recognition, advantages, and disadvantages have been discussed in detail to showcase the enormous potential of nanodiagnostics in human and veterinary medicine. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Biosensing. © 2020 Wiley Periodicals LLC.
Recuperating Biopharmaceutical Aspects of Amphotericin B and Paromomycin Using a Chitosan Functionalized Nanocarrier via Oral Route for Enhanced Anti-leishmanial Activity
(Frontiers Media S.A., 2020) Shabi Parvez; Ganesh Yadagiri; Archana Karole; Om Prakash Singh; Anurag Verma; Shyam Sundar; Shyam Lal Mudavath
The design and development of new pharmaceutical formulations for the existing anti-leishmanial is a new strategic alternate to improve efficacy and safety rather than new drug discovery. Herein hybrid solid lipid nanoparticles (SLN) have been engineered to direct the oral delivery of two anti-leishmanial drugs amphotericin B (AmB) and paromomycin (PM). The combinatorial nanocarriers consist of conventional SLN, antileishmanial drugs (AmB and PM) which have been functionalized with chitosan (Cs) grafted onto the external surface. The Cs-SLN have the mean particle size of 373.9 ± 1.41 nm, polydispersity index (PDI) of 0.342 ± 0.02 and the entrapment efficiency for AmB and PM was found to be 95.20 ± 3.19% and 89.45 ± 6.86 %, respectively. Characterization of SLN was performed by scanning electron microscopy and transmission electron microscopy. Complete internalization of the formulation was observed in Caco-2 cells. Cs-SLN has shown a controlled and slow drug release profile over a period of 72 h and was stable at gastrointestinal fluids, confirmed by simulated gastro-intestinal fluids study. Cs coating enhanced the mucoadhesive property of Cs-SLN. The in-vitro anti-leishmanial activity of Cs-SLN (1 μg/ml) has shown a maximum percentage of inhibition (92.35%) on intra-cellular amastigote growth of L. donovani. © Copyright © 2020 Parvez, Yadagiri, Karole, Singh, Verma, Sundar and Mudavath.
Sensible graphene oxide differentiates macrophages and: Leishmania: a bio-nano interplay in attenuating intracellular parasite
(Royal Society of Chemistry, 2020) Aakriti Singh; Sandeep Sharma; Ganesh Yadagiri; Shabi Parvez; Ritika Gupta; Nitin Kumar Singhal; Nikhil Koratkar; Om Prakash Singh; Shyam Sundar; Vijayakumar Shanmugam; Shyam Lal Mudavath
Leishmania is an obligate intracellular protozoan parasite, which resides in human macrophage vacuoles that are referred to as parasitophorus vacuoles. Amphotericin B (AmB) is the first-line drug with 99% cure rates; however, overdose-induced toxic side effects are a major limitation. To improve the efficacy at lower dose and subsequently to avoid toxicity and to further investigate the role of charge dynamics on the efficacy, a graphene oxide (GO)-based composite of AmB was developed with native negatively charged GO and amine-conjugated positively charged AGO. The AGO composite resulted in enhanced uptake as confirmed by confocal and FACS analysis. Thus, AGO caused a strong inhibition of amastigotes, with IC50 values 5-fold lower than free AmB. The parasitophorus vacuoles harbour a hydrolytic and acidic environment, which is favourable for the parasites, as they don't attenuate this condition. AGO-AmB was able to modify the intracellular pH of the Leishmania donovani-infected macrophages, generating unfavourable conditions for the amastigote, and thus improving its efficacy. © The Royal Society of Chemistry.
Vaccine human clinical trial
(Elsevier, 2022) Bhawana Singh; Shyamali; Dharmendra Kumar Maurya; Rajiv Kumar; Shashi Bhushan Chauhan; Shyam Lal Mudavath; Ram Niwas Meena; Shyam Sundar; Om Prakash Singh
Globally incidence of infectious diseases has declined over the past decades, but still, they continue to have major public health and economic costs. Treatment of infectious diseases is complicated by patients’ late presentation at an advanced stage of their illness. Other challenges include high cost of treatment (drug and hospitalization) and increasing drug resistance. Because of this lack of effective, affordable, minimally toxic drug therapies, an effective vaccine to control infectious diseases is needed. The development of a prophylactic vaccine would prove to be the most effective strategy of disease control and one of the most cost-effective investments in the health sector. However, each newly developed vaccine needs to be evaluated for safety, immunogenicity, and prophylactic efficacy in humans before it is licensed for public use. In this book chapter, we discuss the key elements that should be considered to conduct the vaccine clinical trials against infectious diseases including COVID-19. © 2022 Elsevier Inc. All rights reserved.