Browsing by Author "Brahmeshwar Mishra"

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A novel nanotherapeutic approach: Dual action of green-synthesized silver nanoparticles from Clerodendrum serratum against MDR-ESKAPE pathogens with wound healing potential
(Editions de Sante, 2025) Ritu Raj Patel; Pandey Priya Arun; Vidyasagar; Aradhana Mishra; Sudhir Kumar Singh; Samer Singh; Brahmeshwar Mishra; Meenakshi Singh
The rapid emergence of multidrug-resistant (MDR) ESKAPE pathogens in healthcare settings, particularly chronic wound infections presents a critical challenge. Moreover, with antibiotic resistance reaching alarming levels and conventional treatments failing against biofilm-associated infections, there is an urgent need to develop novel and effective therapeutic strategies. In this study, silver nanoparticles (AgNPs) synthesized via a green method using Clerodendrum serratum leaf extract, along with their polyethylene glycol-coated derivative (PEG-AgNPs), were evaluated for their antibacterial and wound-healing potential. PEG-AgNPs demonstrated superior antibacterial efficacy, with significantly lower minimum inhibitory concentration (MIC) values (0.3906–12.5 μg/mL) compared to AgNPs (3.125–25 μg/mL). Time-kill studies further confirmed that PEG-AgNPs exhibited enhanced bactericidal properties. Mechanistic investigations revealed that their antibacterial activity resulted from bacterial cell membrane rupture, leading to cytoplasmic content leakage, as confirmed by FACS analysis. Furthermore, biofilm formation by these pathogens was evaluated, and the nanoparticles demonstrated remarkable anti-biofilm potency, particularly against Acinetobacter baumannii and Pseudomonas aeruginosa. The LC-MS analysis of C. serratum leaf extract revealed bioactive phytoconstituents, which were subjected to molecular docking studies against biofilm-forming factors in P. aeruginosa and A. baumannii confirming strong binding interactions. Additionally, the prepared nanoparticle-based gel formulations significantly enhanced in vivo wound healing in both uninfected and infected (A. baumannii and P. aeruginosa) wounds, highlighting their potential as dual-action therapeutic agents for inhibiting MDR pathogens and simultaneously promoting tissue regeneration. Therefore, these findings suggest that green synthesized nanoparticles, particularly PEG-AgNPs hold promise as novel interventions for combating MDR-ESKAPE infected wounds. © 2025 Elsevier B.V.
Cabazitaxel-loaded redox-responsive nanocarrier based on d-alpha-tocopheryl-chitosan and hyaluronic acid for improved anti-tumor efficacy in DMBA-induced breast cancer model
(Royal Society of Chemistry, 2024) Abhishek Jha; Manish Kumar; Pooja Goswami; Kanchan Bharti; Manjit Manjit; Ashutosh Gupta; Sudheer Moorkoth; Biplob Koch; Brahmeshwar Mishra
The study involved the formulation of cabazitaxel loaded d-alpha-tocopheryl succinate/chitosan conjugate (CSVE) and hyaluronic acid (HA) based redox-responsive nanoparticles crosslinked using 3,3′-dithiodipropionic acid (DTPA). The nanoparticle surface was functionalized with cetuximab (Cmab) to give CSVE/HA/DTPA/Cmab NP for EGFR targeted delivery of the payload. The formulations were subjected to particle analysis, morphological assessment, solid-state characterization, and in vitro drug release studies. The results showed cationic, sub-200 nm sized spherical particles with the glutathione-responsive release of cabazitaxel. In vitro studies revealed a marked decrease in the IC50 value, improved cellular uptake, and a superior apoptotic effect. To determine the in vivo efficacy of the formulation, pharmacokinetic assessment, tumor regression analysis, and survival analysis were performed. The nanoparticles showed improved pharmacokinetic and anti-tumor efficacy compared to free cabazitaxel. The prepared nanoparticles demonstrated immense potential in targeted delivery of the payload for enhanced breast cancer therapy. © 2024 RSC.
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.
Curcumin quantum dots mediated degradation of bacterial biofilms
(Frontiers Media S.A., 2017) Ashish K. Singh; Pradyot Prakash; Ranjana Singh; Nabarun Nandy; Zeba Firdaus; Monika Bansal; Ranjan K. Singh; Anchal Srivastava; Jagat K. Roy; Brahmeshwar Mishra; Rakesh K. Singh
Bacterial biofilm has been reported to be associated with more than 80% of bacterial infections. Curcumin, a hydrophobic polyphenol compound, has anti-quorum sensing activity apart from having antimicrobial action. However, its use is limited by its poor aqueous solubility and rapid degradation. In this study, we attempted to prepare quantum dots of the drug curcumin in order to achieve enhanced solubility and stability and investigated for its antimicrobial and antibiofilm activity. We utilized a newer twostep bottom up wet milling approach to prepare Curcumin Quantum Dots (CurQDs) using acetone as a primary solvent. Minimum inhibitory concentration against select Gram-positive and Gram-negative bacteria was performed. The antibiofilm assay was performed at first using 96-well tissue culture plate and subsequently validated by Confocal Laser Scanning Microscopy. Further, biofilm matrix protein was isolated using formaldehyde sludge and TCA/Acetone precipitation method. Protein extracted was incubated with varying concentration of CurQDs for 4 h and was subjected to SDS–PAGE. Molecular docking study was performed to observe interaction between curcumin and phenol soluble modulins as well as curli proteins. The biophysical evidences obtained from TEM, SEM, UV-VIS, fluorescence, Raman spectroscopy, and zeta potential analysis confirmed the formation of curcumin quantum dots with increased stability and solubility. The MICs of curcumin quantum dots, as observed against both select gram positive and negative bacterial isolates, was observed to be significantly lower than native curcumin particles. On TCP assay, Curcumin observed to be having antibiofilm as well as biofilm degrading activity. Results of SDS–PAGE and molecular docking have shown interaction between biofilm matrix proteins and curcumin. The results indicate that aqueous solubility and stability of Curcumin can be achieved by preparing its quantum dots. The study also demonstrates that by sizing down the particle size has not only enhanced its antimicrobial properties but it has also shown its antibiofilm activities. Further, study is needed to elucidate the exact nature of interaction between curcumin and biofilm matrix proteins. © 2017 Singh, Prakash, Singh, Nandy, Firdaus, Bansal, Singh, Srivastava, Roy, Mishra and Singh.
Design and characterization of anti-microbial novel herbal nanofiber scaffolds for the management of periodontal diseases
(Nature Research, 2025) Pragati Dubey; Neelam Mittal; Brahmeshwar Mishra; S. Manjit; Pooja Goswami; Biplob Koch; Anju Gautam; Pradeep Harish Kumar; Kavindra Nath Tiwari
Design and evaluation of PCL and gelatin loaded nanofiber containing herbal formulation named Ashvakatri in the treatment of chronic periodontitis. The electro-spinning method was used to create the composite nano-fibers containing herbal formulation, which were then evaluated for various parameters including in-vitro antimicrobial study and in-vitro drug release. An interconnected, continuous and bead free nanofiber with an average diameter of 150–250 nm was exhibited by the optimized nanofiber. The addition of gelatin and PCL to the optimized nanofiber improved its biocompatibility and bioadhesive characteristics. According to anti-microbial investigation and CLSM study indicated the remarkable inhibition of periodontal pathogens such as Aggregabacter actinomycetemcomitans (AI), Porphyromonas Gingivilis (PG), Fusobacterium spp (FB), and Porphyromonas intermedia (PI) respectively by optimized nanofiber and in-vitro drug release study also demonstrated the controlled release of composite nanofiber for over 220 h. Additionally, the MTT assay and in-vitro scratch assay indicated the composite NF had no cytotoxicity to the fibroblast cell line. The fabricated NF is a potential option for chronic periodontitis treatment since it expedited anti-bacterial, cytotoxic and sustained release medications. © The Author(s) 2025.
Design and development of a poly-herbal spray formulation and its physicochemical and biological profiling: from classic to modern drug delivery system
(National Institute of Science Communication and Policy Research, 2024) Shruti Pandey; Shardendu Mishra; Brahmeshwar Mishra; Anand Kumar Chaudhary
Many of the polyherbal formulations are described in ayurvedic classics for inflammation and pains. Among them rasna saptak kwath gives best therapeutic effect in clinical studies but palatable issue makes it less popular among patients. The present work emphasizes on the transformation of this classical formulation into more convenient and acceptable form for the patients without disturbing its efficacy. In the present study kwath was converted into mechanical spray form for pain and inflammation. The extractions of herbs were done by both classical and modern methods. The mechanical spray solution was prepared with permeation enhancer, humectant, in suitable solvent system. The spray was standardized on various parameters like viscosity, evaporation time, and spray pattern. Spray was also evaluated for in vitro drug release, anti inflammatory, analgesic and skin irritation study. In the result, the spray pattern was found uniform and evaporation time was 9.81±0.30 min. The fluxes for spray were found to be 2.82±.0.11 (µg/cm2/h). The kinetic model for spray best fitted to zero order permeation at a constant flux for spray r>0.98. The spray also provides good results in pain and inflammation. So, here is the possibility of replacing that sticky oil of Ayurveda with spray for good relief. The products show the path for a new generation of Ayurvedic dosage form, which has the bright future in this busy schedule of life where integrity of Ayurvedic medicines not hampered. © 2024, National Institute of Science Communication and Policy Research. All rights reserved.
Design, optimization and characterizations of chitosan fortified calcium alginate microspheres for the controlled delivery of dual drugs
(Taylor and Francis Ltd., 2018) Sarita Kumari Yadav; Gayasuddin Khan; Gunjan Vasant Bonde; Monika Bansal; Brahmeshwar Mishra
Periodontal disease is chronic, highly prevalent infectious disease that requires prolonged and controlled delivery of antimicrobial agents into pockets. To achieve this objective, dual antimicrobials encapsulated chitosan fortified calcium alginate (CS-Ca-SA) microspheres were formulated by application of Plackett-Burman factorial design. The microspheres were optimized for particle size (PS), entrapment efficiency (EE) and drug release. The optimized microspheres presented average PS of 74–461 µm and EE of 62.45–86.20% with controlled drug delivery for 120 hours. FTIR disclosed successful complexation between SA and CS. DSC and XRD studies showed changes in the crystallinity of drugs in microspheres. Shape factor and SEM demonstrated spherical to pear-shaped microspheres. Release exponent >0.43 and high diffusion coefficients revealed non-Fickian-based diffusion-limited drug release. CS-Ca-SA microspheres exhibited surface pH of 6.5 ± 0.5, moderate swelling, less erosion and improved mucoadhesion over Ca-SA microspheres. Also, significant antimicrobial activity against Escherichia coli and Staphylococcus aureus and cytocompatibility with L929 cell lines were observed. Further, microspheres exhibited long-term stability on refrigeration. The outcomes of study supported the potential of dual polymer and dual drug-based biodegradable, stable, non-toxic, mucoadhesive, controlled and prolonged drug release microspheres as more patient compliant by administration into periodontal pockets for the management of periodontal disease. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology
(Croatian Pharmaceutical Society, 2009) Pramod Kumar; Sanjay Singh; Brahmeshwar Mishra
Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax, tmax, AUC 0-24, MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.
Development and biopharmaceutical evaluation of osmotic pump tablets for controlled delivery of diclofenac sodium
(Croatian Pharmaceutical Society, 2003) Meena Rani; Rahul Surana; Chelladurai Sankar; Brahmeshwar Mishra
Based on the principles of an elementary osmotic pump (OP), OP tablets were designed and evaluated with the aim to deliver diclofenac sodium (DS) in a controlled manner. In vitro evaluation was done in various release media and kinetics was evaluated using the regression coefficient analysis. Effects of orifice size, coating membrane type, coating thickness, static and stirred conditions and pH variation were studied. In vivo evaluation was performed on six healthy human volunteers and various pharmacokinetic parameters (C max, tmax, AUC0-24, MRT) and relative bioavailability were calculated. The results were compared with the performance of two commercial tablets of DS. The drug release from OP tablets was dependent on the type and thickness of the coating membrane, but was independent of the orifice size and static and stirred conditions of the release medium. The OP tablets provided a prolonged and controlled DS release compared to commercial sustained-release and conventional tablets of DS.
Development and Evaluation of Biodegradable Chitosan Films of Metronidazole and Levofloxacin for the Management of Periodontitis
(Springer New York LLC, 2016) Gayasuddin Khan; Sarita K. Yadav; Ravi R. Patel; Gopal Nath; Monika Bansal; Brahmeshwar Mishra
Metronidazole (MZ) and levofloxacin (LF) are widely employed for treatment of periodontitis, but high oral dose and resistance development after long-term oral administration limit their use. The aim of this study was to alleviate shortcomings in the treatment of periodontitis by fabrication of intrapocket, biodegradable films of chitosan (CS) loaded with MZ and LF meant for inserting into periodontal pockets to treat infections. The films were developed by solvent casting technique using propylene glycol as plasticizer and glutaraldehyde as crosslinking agent. Their physical characteristics, such as drug content, surface pH, swelling index, and folding endurance, exhibited results within limit. Further, FTIR and DSC studies revealed stability of films and compatibility between drugs and excipients. SEM images of films showed the presence of free drug particles on the surface causing burst effect. In vitro release in McIlvaine buffer pH 6.6 was of sustained nature assisted by the burst effect. CS and crosslinking agent concentrations negatively affected drug release and positively affected T90 (time for releasing 90% of the drug) due to altered matrix density. In contrast, the plasticizer concentration increases membrane permeability and hence increased drug release, lowering T90. Crosslinked films demonstrated sustained release up to 7 days. The antibacterial efficacy of films was tested on Staphylococcus aureus and Escherichia coli, indicating good antibacterial activity. Clinical trials on patients proved the therapeutic efficacy of the films by a significant (p < 0.05) decrease in the clinical markers of periodontitis, i.e. gingival index, plaque index and pocket depth. Conclusively, the films of MZ and LF were successful tools for the management of periodontitis. © 2015, American Association of Pharmaceutical Scientists.
Development and in vitro evaluations of gelatin a microspheres of ketorolac tromethamine for intranasal administration
(Croatian Pharmaceutical Society, 2003) Chelladurai Sankar; Brahmeshwar Mishra
Gelatin A microspheres (MS) of ketorolac tromethamine (KT) for intranasal systemic delivery were developed with the aim to avoid gastro-intestinal complications, to improve patient compliance, to use as an alternative therapy to conventional dosage forms, to achieve controlled blood level profiles, and to obtain improved therapeutic efficacy in the treatment of postoperative pain and migraine. Gelatin A microspheres were prepared using the emulsification-crosslinking technique. The drug was dispersed in polymer gelatin and formulated into a w/o emulsion with liquid paraffin, using glutaraldehyde as a crosslinking agent. The formulation variables were drug loading and the concentrations of polymer (gelatin), copolymer (chitosan) and the crosslinking agent. All the prepared microspheres were evaluated for physical characteristics, such as particle size, incorporation efficiency, swelling ability, in vitro bioadhesion on rabbit small intestine and in vitro drug release characteristics in pH 6.6 phosphate buffer. All the microspheres showed good bioadhesive properties. Gelatin A and chitosan concentrations, percentage of the crosslinking agent and also the drug loading affected significantly the rate and extent of drug release. The data indicated that the KT release followed Higuchi's matrix model.
Development, optimization and evaluation of curcumin loaded biodegradable crosslinked gelatin film for the effective treatment of periodontitis
(Taylor and Francis Ltd., 2018) Sheetal Chauhan; Monika Bansal; Gayasuddin Khan; Sarita K. Yadav; Ashish K. Singh; Pradyot Prakash; Brahmeshwar Mishra
Objective: Aim of the present study was to prepare curcumin (CUR) loaded biodegradable crosslinked gelatin (GE) film to alleviate the existing shortcomings in the treatment of periodontitis. Significance: Gelatin film was optimized to provide anticipated mucoadhesive strength, mechanical properties, folding endurance, and prolonged drug release over treatment duration, for successful application in the periodontitis. Methods: The film was developed by using solvent casting technique and “Design of Experiments” approach was employed for evaluating the influence of independent variables on dependent response variables. Solid-state characterization of the film was performed by FTIR, XRD, and SEM. Further, prepared formulations were evaluated for drug content uniformity, surface pH, folding endurance, swelling index, mechanical strength, mucoadhesive strength, in vitro biodegradation, and in vitro drug release behavior. Results: Solid state characterization of the formulation showed that CUR is physico-chemically compatible with other excipients and CUR was entrapped in an amorphous form inside the smooth and uniform film. The optimized film showed degree of crosslinking 51.04 ± 2.4, swelling index 138.10 ± 1.25, and folding endurance 270 ± 3 with surface pH around 7.0. Crosslinker concentrations positively affected swelling index and biodegradation of film due to altered matrix density of the polymer. Results of in vitro drug release demonstrated the capability of the developed film for efficiently delivering CUR in a sustained manner up to 7 days. Conclusions: The developed optimized film could be considered as a promising delivery strategy to administer medicament locally into the periodontal pockets for the safe and efficient management of periodontitis. © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Evaluation of nanofiber scaffolds laden Ashvakatri in the management of chronic periodontitis-a randomized, controlled split pocket study
(Elsevier B.V., 2025) Pragati Dubey; Neelam Mittal; Brahmeshwar Mishra; Anju Gautam; Naveen P.G. Kumar; M. Rashika
Background: The main objective of periodontal treatment is to stop the progression of periodontal disease. Controlled-release drugs yield promising outcomes when conventional treatment is proven to be insufficient in establishing periodontal health in chronic periodontitis. A low-dose controlled-release delivery method for the treatment of periodontal infection was attempted to be developed in this study. With effective electrospinning, a novel sustained-release medication system including polycaprolactone (PCL) nanofibers containing Ashvakatri (A2) and Tetracycline (TET) was accessed clinically for periodontitis. Method & materials: The electrospinning technique prepared nanofibers with A2 and TET in PCL and gelatin. The A2-loaded nanofiber followed the Higuchi model release and had a sustained impact of 9 days (220 h). 75 periodontal sites from 31 patients with chronic periodontitis (≥5 mm probing depth) followed by 3 groups: Group I received Scaling and root planning (SRP) and blank polymer mat whereas Group II treated with SRP and PCL-GE-A2 nanofiber scaffold/mat, and Group III received SRP + PCL-GE-TET (tetracycline) nanofiber scaffolds. Clinical evaluations of GI, PI, PPD, and CAL were performed on each patient group. Conclusion: Compared to the placebo and standard group, the test group was remarkably associated with improved GI, PI, PPD, and CAL at the end of the study. Therefore, drug-loaded nanofiber was found to be efficacious in treating periodontal diseases and may be appropriate as an alternative treatment. Clinical significance: The fabricated PCL-GE-A2 nanofiber mat was more cost-efficient, minimized the dosage amount, and dosage frequency, and showed no adverse effects or discomforts with increased patient compliance. © 2025 The Authors
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.
Fabrication of lipid-modified drug nanocrystals loaded injectable hydrogel for breast cancer therapy
(Springer, 2025) Manish Kumar; Abhishek Jha; Pooja Goswami; Ritika Srivastava; Manjit Manjit; Kanchan Bharti; Biplob Koch; Brahmeshwar Mishra
The current study includes the design of soluplus stabilized, lipid-coated, and fucoidan-oleylamine conjugate modified paclitaxel nanocrystals. The nanocrystals (Lipid-NCs) were about 100 nm, homogeneous, stable and showed improved drug release compared to pure PTX. The nanocrystals were subsequently loaded in an in situ gel-forming hydrogel for the intratumoral injection. The resulting hydrogel exhibited a sol-form at the lower temperature of 2–8 °C while converted to a gel-form at the body temperature. The injectable hydrogel had a reasonable viscosity, an acceptable pH, good syringeability, and a quick sol–gel transition. The hydrogel demonstrated high payload potential, homogeneous distribution, and controlled long-term drug release. In vivo studies revealed the higher efficacy of Lipid-NCs hydrogel in tumor inhibition while avoiding systemic toxicity, compared to pure PTX-loaded hydrogel and intravenously administered PTX. In conclusion, nanocrystal-loaded hydrogel is a promising localized drug delivery system for breast cancer therapy. © The Author(s) 2025.
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.
Formulation and evaluation of cetuximab functionalized phospholipid modified nanocrystals of paclitaxel for non-small cell lung cancer therapy
(Nature Research, 2024) Manish Kumar; Pooja Goswami; Abhishek Jha; Manjit Manjit; Amol Parasram Satpute; Biplob Koch; Brahmeshwar Mishra
Present work aims to prepare Soluplus stabilized, phospholipid-modified, and cetuximab-conjugated paclitaxel nanocrystals (NCs) as stable nanocarriers for targeted drug delivery. The NCs, prepared using concurrent antisolvent precipitation cum cold crystallization method followed by probe sonication, were found to be monodispersed particles with sub-200 nm size. The microscopic analysis uncovered rod and spherical anisotropy for Soluplus stabilized (PTX-NCs) and phospholipid modified (Lipid/PTX-NCs) nanocrystals, respectively. The formation of amorphous PTX-NCs and subsequent coating with phospholipid was confirmed by solid-state characterization using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform Infrared Spectroscopy (FTIR). X-ray Photoelectron Spectroscopic (XPS) analysis, indicated successful conjugation of cetuximab on NCs surface. Lipid coating rendered a sustained drug release behaviour to NCs at physiological pH. In vitro cell line studies confirmed the improved cellular internalization and better apoptosis induction capability of NCs, consequently resulting in enhanced efficacy of PTX against A549 cancer cells. Moreover, in Benzo[a] pyrene-induced lung cancer model, Cmab/Lipid/PTX-NCs showed significant improvement in tumor inhibition potential in comparison to pure PTX. The prepared Cmab/Lipid/PTX-NCs also exhibited improved pharmacokinetics performance, avoided off-target distribution, and showed a reduction in systemic toxicity. The findings of this study indicate the promising potential of the prepared cetuximab-functionalized phospholipid-coated paclitaxel nanocrystals in lung cancer therapy. © The Author(s) 2024.
Formulation and Evaluation of Lipid/Soluplus-Stabilized Nanocrystals of Paclitaxel and Bosutinib for a Synergistic Effect in Non-Small Cell Lung Cancer Therapy
(American Chemical Society, 2025) Manish Kumar; Pooja Goswami; Abhishek Jha; Vividha S. Dhapte-Pawar; Biplob Koch; Brahmeshwar Mishra
Tyrosine kinase inhibitors have been employed for the treatment of lung cancer, owing to their role in regulating irregulated pathways or mutated genes. Bosutinib, a nonreceptor tyrosine kinase, has been recently investigated for lung cancer treatment. Bosutinib can also be used with paclitaxel as a combinatorial approach to receive a synergistic effect for the effective management of lung cancer. Furthermore, the nanocrystals of each can also be prepared and in combination can produce a more pronounced impact than the drug combination. Herein, the prepared Soluplus/lipid-stabilized nanocrystals of paclitaxel and bosutinib were rod to cubic in shape of about 150-250 nm. The nanocrystals were stable, provided controlled drug release, and exhibited a higher aerosolization performance. The nanocrystal combination demonstrated higher anticancer activity than the drug combination synergy against A549 cancer cells. The nanocrystals increased the level of cellular internalization in cancer cells, thereby inducing higher ROS generation and apoptosis of cancer cells. Furthermore, the lipid/Soluplus-stabilized nanocrystals exhibited higher translocation potential compared with only Soluplus-stabilized nanocrystals. The nanocrystals administered intratracheally showed a lower drug distribution to other organs, with prolonged drug retention in the lungs, suggesting the higher efficacy of developed nanocrystals in targeting the lungs. In conclusion, lipid-modified nanocrystals can be a novel approach for the effective management of lung cancer. © 2025 American Chemical Society.
Hyaluronic acid-oleylamine and chitosan-oleic acid conjugate-based hybrid nanoparticle delivery via. dissolving microneedles for enhanced treatment efficacy in localized breast cancer
(Elsevier Ltd, 2024) Abhishek Jha; Manish Kumar; Pooja Goswami; Manjit Manjit; Kanchan Bharti; Biplob Koch; Brahmeshwar Mishra
Microneedle technology offers a minimally invasive treatment strategy to deliver chemotherapeutics to localized tumors. Amalgamating the surface functionalized nanoparticles with microneedle technology can potentially deliver drugs directly to tumors and subsequently target cancer cells via, overexpressed receptors on the cell surface, thereby enhancing the treatment efficacy while reducing side effects. Here, we report cetuximab anchored hyaluronic acid-oleylamine and chitosan-oleic acid-based hybrid nanoparticle (HA-OA/CS-OA NPT)-loaded dissolving microneedles (MN) for targeted delivery of cabazitaxel (CBT) in localized breast cancer tumor. The HA-OA/CS-OA NPT was characterized for their size, surface charge, morphology, physicochemical characteristics, drug release behavior, and in vitro anti-cancer efficacy. The HA-OA/CS-OA NPT were of ~125 nm size, showed enhanced cytotoxicity and cellular uptake, and elicited a superior apoptotic response against MDA-MB-231 cells. Subsequently, the morphology and physicochemical characteristics of HA-OA/CS-OA NPT-loaded MN were also evaluated. The fabricated microneedles were of ~550 μm height and showed loading of nanoparticles equivalent to ~250 μg of CBT. The ex vivo skin permeation study revealed fast dissolution of microneedles upon hydration, while the drug permeation across the skin exhibited ~4-fold improvement in comparison to free drug-loaded MN. In vivo studies performed on DMBA-induced breast cancer in female SD rats showed a marked reduction in tumor volume after administration of drug and nanoparticle-loaded microneedles in comparison to intravenous administration of free drug. However, the HA-OA/CS-OA NPT-MN showed the highest tumor reduction and survival rate, with the lowest body weight reduction in comparison to other treatment groups, indicating its superior efficacy and low systemic toxicity. Overall, the dissolving microneedle-mediated delivery of targeted nanoparticles loaded with chemotherapeutics offers a superior alternative to conventional intravenous chemotherapy. © 2024 Elsevier B.V.