Browsing by Author "Krishan Kumar"

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A Comprehensive Review on Microbubble Concept, Development and Its Application in Therapeutic Drug Delivery and Clinical Management of Disease
(NLM (Medline), 2021) Sandeep Rathor; Sheikh Aamir; Dinesh C. Bhatt; Krishan Kumar; Vikash Kumar
BACKGROUND: The general purpose of this review was to briefly describe the Gastro-Retentive Drug Delivery System (GRDDS) and to primarily focus on mechanisms of flotation for gastric retention. METHODS: The principle mechanism of Floating Drug Delivery Systems (FDDS) is mainly based on hydro-dynamically controlled low-density system, which gets swollen when comes in contact with the gastric environment and remains buoyant for an extended period of time with improved bioavailability and therapeutic efficacy. The main perspective of this review was to focus on microbubble drug delivery due to its wide range of applications. RESULTS: Microbubble is a new, economically viable, and non-invasive technique that is alternative to conventional techniques. The size of microbubbles ranges from 1-100 micrometers, which contain oxygen or air and remain suspended for prolonged drug release. Due to its great potential, microbubble is used in the therapeutic delivery of drug molecules or genetic material at their specific targeted site in various diseases. The recent research also suggests that ultrasound-mediated microbubble is more frequently used in the biomedical field for imaging of site-specific molecule targeting for the detection of disease and site-specific drug delivery. CONCLUSION: Gastro-retentive floating drug delivery system was considered as the most favorable approach for site-specific drug delivery. But nowadays, microbubble is gaining more popularity for its potential applications in the biomedical field. In recent years, there is much progress in microbubble for site-specific delivery of a drug or genetic material. Recent research also suggests that the ultrasound- mediated microbubble has shown a positive impact on the diagnosis and clinical management of various diseases such as liver cirrhosis, brain tumor, ocular, and urinary tract infection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy
(American Chemical Society, 2025) Krishan Kumar; Manjit Saini; Varsha Rani; Mohini Mishra; None Priya; None Jatin; Siddharth Tiwari; Brahmeshwar Mishra; Ruchi Chawla
The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. The prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified PLGA-NPs exhibited a uniform polydispersity index (PDI) value below 0.3, a particle size under 200 nm, and negative zeta potentials ranging from −17.45 to −21.45 mV. Entrapment efficiency (% EE) and drug loading values exceeded 70% and 8%, respectively. SEM and TEM showed that the particles were uniformly dispersed with a spherical shape. FTIR, XRD, TGA, and DSC analyses indicated the physiochemical stability of the drug within the nanoformulations. Controlled (26.92 to 31.64% within 24 h at pH 7.4) and pH-sensitive (36.80 to 40.25% within 24 h at pH 5.5) GB release were observed for the different formulations of PLGA-NPs. The MTT cytotoxicity assay revealed IC50 values for the GB control, GB-PLGA-NPs, and GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 ± 1.24, and 4.16 ± 1.05 μg/mL, respectively. The Co6-GB-PLGA-Siac-NPs showed significantly higher cellular uptake than that of the Co6-GB control (p < 0.001) and Co6-GB-PLGA-NPs (p < 0.01) respectively. Pharmacokinetic profiles indicated higher AUC values (ng·h/mL) for GB-PLGA-Siac-NPs (8355.07 ± 2006.45) compared to GB-PLGA-NPs (6145.58 ± 969.25) and the GB control (1510.72 ± 81.08), resulting in higher bioavailability of GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization of DiD-GB-PLGA-Siac-NPs, indicated by radiant efficiency signal on B[a]P induced lung cancerous tissues relative to DiD-GB-PLGA-NPs after 1 h (p < 0.001), 4 h (p < 0.01), and 12 h (p < 0.001), which could be attributed to their ability to target glycans. In vivo anticancer efficacy in a B[a]P-induced lung cancer mice model depicted that GB-PLGA-Siac-NPs effectively inhibited lung cancer cells and reduced systemic toxicity, as evidenced by the average number of lung cancer cells, body weight values, survival analysis, biochemical parameters associated with organs (such as the liver and kidney), and histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles could serve as an efficient vehicle for GB delivery via targeting glycan receptors in lung cancer therapy. © 2025 American Chemical Society.
Dual targeting pH responsive chitosan nanoparticles for enhanced active cellular internalization of gemcitabine in non-small cell lung cancer
(Elsevier B.V., 2023) Krishan Kumar; Shiv Govind Rawat; Manjit; Mohini Mishra; Priya; Ajay Kumar; Ruchi Chawla
Lung cancer (LC), related with the enhanced expression of epidermal growth factor receptor (EGFR) and sialic acid binding receptors (glycan) brought about the development of EGFR and glycan receptor specific anticancer therapeutics. The current study assessed the formulation, physiochemical characterization, in vitro and in vivo effects of sialic acid (SA) and cetuximab (Cxmab) decorated chitosan nanoparticles (CSN-NPs) loaded with gemcitabine (GMC) targeted to glycan and EGFR over-expressing non-small-cell lung-cancer (NSCLC) A-549 cells. Chitosan (CSN) was conjugated with sialic acid via EDC/NHS chemistry followed by gemcitabine loaded sialic acid conjugated chitosan nanoparticles (GMC-CSN-SA-NPs) were prepared by ionic gelation method decorated with Cxmab by electrostatic interaction. In vitro cytotoxicity of NPs quantified using cell based MTT, DAPI and Annexing-V/PI apoptosis assays showed superior antiproliferative activity of targeted nanoformulations (GMC-CSN-SA-Cxmab-NPs ≫ GMC-CSN-SA-NPs, GMC-CSN-Cxmab-NPs) over non-targeted nanoformulation (GMC-CSN-NPs) against A-549 cells. In vivo pharmacokinetic study showed superior bioavailability and in vivo therapeutic efficacy investigation exhibited strongest anticancer activity of glycan and EGFR targeted NPs (GMC-CSN-SA-Cxmab-NPs). GMC-CSN-SA-Cxmab-NPs demonstrated enhanced cellular internalization and better therapeutic potential, by specifically targeting glycan and EGFR on NSCLC A-549 cells and B[a]P induced lung cancer mice model, hence it might be a good substitute for non-targeted, conventional chemotherapy. © 2023 Elsevier B.V.
Fabrication of dual drug-loaded polycaprolactone–gelatin composite nanofibers for full thickness diabetic wound healing
(Newlands Press Ltd, 2024) Manjit Manjit; Manish Kumar; Krishan Kumar; Madhukiran R. Dhondale; Abhishek Jha; Kanchan Bharti; Zinnu Rain; Pradyot Prakash; Brahmeshwar Mishra
Aim: Design of moxifloxacin and ornidazole co-loaded polycaprolactone and gelatin nanofiber dressing for diabetic wounds. Materials & methods: The composite nanofibers were prepared using electrospinning technique and characterized for in vitro drug release, antibacterial activity, laser doppler and in vivo wound healing. Results: The optimized nanofiber demonstrated an interconnected bead free nanofiber with average diameter <200 nm. The in vitro drug release & antimicrobial studies revealed that optimized nanofiber provided drug release for >120 h, thereby inhibiting growth of Escherichia coli and Stapyhlococcus aureus. An in vivo wound closure study on diabetic rats found that optimized nanofiber group had a significantly higher wound closure rate than marketed formulation. Conclusion: The nanofiber provided prolonged drug release and accelerated wound healing, making it a promising candidate for diabetic wound care. Plain language summary: This article is about making a wound dressing material of tiny fibres that have antibiotic properties to kill microbes at the wound site and make wounds heal faster. This is particularly important for people with diabetes, whose wounds often take longer to heal. The designed nanofibrous dressing releases antibiotic drugs at the wound site for more than 120 h, killing harmful microbes and thus avoiding their invasion at wound site. Also, animal experiments showed that the nanofibers shorten the time wounds take to heal by providing a suitable surface and a favourable environment for wound healing. The study concludes that the fabricated nanofiber dressing helps complex wounds heal faster, and could be a strong new dressing material for diabetic wound care. C 2023 Newlands Press.
Fabrication of gelatin coated polycaprolactone nanofiber scaffolds co-loaded with luliconazole and naringenin for treatment of Candida infected diabetic wounds
(Elsevier B.V., 2024) Manjit Manjit; Krishan Kumar; Manish Kumar; Abhishek Jha; Kanchan Bharti; Punit Tiwari; Ragini Tilak; Virendra Singh; Biplob Koch; Brahmeshwar Mishra
The current study focuses on the development of gelatin-coated polycaprolactone (PCL) nanofibers co-loaded with luliconazole and naringenin for accelerated healing of infected diabetic wounds. Inherently, PCL nanofibers have excellent biocompatibility and biodegradation profiles but lack bioadhesion characteristics, which limits their use as dressing materials. So, coating them with a biocompatible and hydrophilic material like gelatin can improve bioadhesion. The preparation of nanofibers was done with the electrospinning technique. The solid state characterization and in-vitro performance assessment of nanofibers indicate the formation of uniformly interconnected nanofibers of 200–400 nm in diameter with smooth surface topography, excellent drug entrapment, and a surface pH of 5.6–6.8. The antifungal study showed that the nanofiber matrix exhibits excellent biofilm inhibition activity against several strains of Candida. Further, in-vivo assessment of nanofiber performance on C. albicans infected wounds in diabetic rats indicated accelerated wound healing efficacy in comparison to gauge-treated groups. Additionally, a higher blood flow and rapid re-epithelialization of wound tissue in the treatment group corroborated with the results obtained in the wound closure study. Overall, the developed dual-drug-loaded electrospun nanofiber mats have good compatibility, surface properties, and excellent wound healing potential, which can provide an extra edge in the management of complex diabetic wounds. © 2024 Elsevier B.V.
Factorial Design-Based Nanocarrier Mediated Formulation of Efavirenz and Its Characterization
(World Scientific, 2022) Ruchi Chawla; Venkatanaidu Karri; Varsha Rani; Mohini Mishra; Krishan Kumar
Efavirenz (EFV) suffers from poor aqueous solubility which results in low bioavailability of the drug. Nanocarrier-based drug delivery systems offer a suitable alternative for improving the physico-chemical properties of the drug and hence its efficacy. Nanosuspension (NS) of EFV was formulated by solvent-anti solvent precipitation method using PVP K-30 as stabilizer and sodium lauryl sulphate (SLS) as the wetting agent. Multi-level factorial design was applied to select the optimal formulation which was further characterized. The optimal batch exhibited mean particle size of 305nm and polydispersity index (PDI) of 0.345. Solid-state characterization studies of the NS conducted using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction, and differential scanning calorimetry (DSC) revealed compatibility between the drug and the excipients and modest alteration in the crystallinity of the drug. There was progressive increase in the solubility of the drug when incorporated in NS from 17.39μg/ml to 256μg/ml. Further, drug release studies showed significantly better and controlled drug release pattern in comparison to the free drug due to the presence of nanosized particles in the formulation. © 2022 World Scientific Publishing Company.
Formulation and characterization of polyvinyl alcohol/chitosan composite nanofiber co-loaded with silver nanoparticle & luliconazole encapsulated poly lactic-co-glycolic acid nanoparticle for treatment of diabetic foot ulcer
(Elsevier B.V., 2024) Manjit Manjit; Manish Kumar; Abhishek Jha; Kanchan Bharti; Krishan Kumar; Punit Tiwari; Ragini Tilak; Virendra Singh; Biplob Koch; Brahmeshwar Mishra
Chronic wounds are prone to fungal infections, possess a significant challenge, and result in substantial mortality. Diabetic wounds infected with Candida strains are extremely common. It can create biofilm at the wound site, which can lead to antibiotic resistance. As a result, developing innovative dressing materials that combat fungal infections while also providing wound healing is a viable strategy to treat infected wounds and address the issue of antibiotic resistance. Present work proposed anti-infective dressing material for the treatment of fungal strains Candida-infected diabetic foot ulcer (DFU). The nanofiber was fabricated using polyvinyl Alcohol/chitosan as hydrogel base and co-loaded with silver nanoparticles (AgNP) and luliconazole-nanoparticles (LZNP) nanoparticles, prepared using PLGA. Fabricated nanofibers had pH close to target area and exhibited hydrophilic surface suitable for adhesion to wound area. The nanofibers showed strong antifungal and antibiofilm properties against different strains of Candida; mainly C. albicans, C. auris, C. krusei, C. parapsilosis and C. tropicalis. Nanofibers exhibited excellent water retention potential and water vapour transmission rate. The nanofibers had sufficient payload capacity towards AgNP and LZNP, and provided controlled release of payload, which was also confirmed by in-vivo imaging. In-vitro studies confirmed the biocompatibility and enhanced proliferation of Human keratinocytes cells (HaCaT). In-vivo studies showed accelerated wound closure by providing ant-infective action, supporting cellular proliferation and improving blood flow, all collectively contributing in expedited wound healing. © 2023 Elsevier B.V.
Optimization of clinical uricase production by Bacillus cereus under submerged fermentation, its purification and structure characterization
(Elsevier Ltd, 2018) S.M. Khade; S.K. Srivastava; Krishan Kumar; Kedar Sharma; Arun Goyal; A.D. Tripathi
The uricase production from Bacillus cereus after statistical optimization of process variables designed by L18 orthogonal array gave enhanced enzyme activity by 13% (29.7 U/mL) as compared with un-optimized medium (26.3 U/mL). The optimized process variables used for scale up of uricase production in a bioreactor gave 39.7 U/mL of uricase activity resulting 51% increase as compared with unoptimized medium. The Luedeking-Piret model classified the uricase production from Bacillus cereus as mixed-growth associated. The culture supernatant having uricase activity (7.7 U/mg) on purification by (NH4)2SO4 precipitation followed by anion-exchange and size-exclusion chromatography resulted 87 U/mg giving 11-fold purification. The purified uricase can be used for treating gout disease. The de novo amino acid sequence analysis of purified uricase by MALDI-TOF MS showed 301 amino acids and molecular mass of 34.4 kDa, which was corroborated by 35 kDa from SDS-PAGE. The phylogenetic tree generated by homologous amino acid sequences displayed the clustering of Bacillus uricase with fungal uricase. The secondary structure analysis of uricase by circular dichroism showed 18.6% α-helices and 27.4% β-strands. These results were corroborated by secondary structure prediction analysis by PsiPred. The homology modelling of uricase displayed the conserved T-fold structure. © 2018 Elsevier Ltd
Organ-targeted drug delivery systems (OTDDS) of poly[(N-acryloylglycine)-co-(N-acryloyl-l-phenylalanine methyl ester)] copolymer library and effective treatment of triple-negative breast cancer
(Royal Society of Chemistry, 2025) Sukanya Patra; None Jyotirmayee; Krishan Kumar; Divya Pareek; Prem Shankar Gupta; Anjali Ramsabad Mourya; Taniya Das; Kirti Wasnik; Malkhey Verma; Ruchi Chawla; Tarun K. Batra; Pradip Paik
Organ-targeted drug delivery systems (OTDDS) are essential for the effective treatment of complicated diseases. Triple-negative breast cancer (TNBC) is an aggressive cancer with high mortality and requires targeted therapeutics. This work was aimed at designing a library of polymeric OTDDS with N-acryloyl-glycine (NAG) and N-acryloyl-l-phenylalanine methyl ester (NAPA) [p(NAG-co-NAPA)(x:y)] and screening its in vivo organ-targeting specificity. Among this library, the best p(NAG-co-NAPA)(x:y) NPs with an x : y ratio of 1 : 4 and size of 160-210 nm targeted breasts to a high extent compared to other organs and thus were optimized for TNBC treatment. A network pharmacology study was performed, which revealed that 14 genes were responsible for TNBC, and a combination of DHA (targets 6 genes) and piperine (targets 8 genes) drugs was used to optimize the formulation, achieving the maximum therapeutic efficiency against TNBC with an IC50 value of 350 μg mL−1. The designed organ-specific polymeric nanoparticle (NP) library, identification of target genes and proteins responsible for TNBC, and the optimized formulation for effective combination therapy established an effective therapeutic option for TNBC. The findings of this work further demonstrate that this polymeric library of NPs shows exciting therapeutic potential for treating TNBC and presents innovative treatment options for critical diseases of the liver, heart, lungs and kidney. © 2025 The Royal Society of Chemistry.