Browsing by Author "Kanchan Bharti"

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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.
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.
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.
Lipid-coated nanocrystals of paclitaxel as dry powder for inhalation: Characterization, in-vitro performance, and pharmacokinetic assessment
(Elsevier B.V., 2024) Manish Kumar; Abhishek Jha; Kanchan Bharti; Manjit Manjit; Pradnya Kumbhar; Vividha Dhapte-Pawar; Brahmeshwar Mishra
Background: Nanocrystals can be produced as a dry powder for inhalation (DPIs) to deliver high doses of drug to the lungs, owing to their high payload and stability to the shear stress of aerosolization force. Furthermore, lipid-coated nanocrystals can be formulated to improve the drug accumulation and retention in lung. Objective: The present work involved the fabrication of paclitaxel nanocrystals using hydrophilic marine biopolymer fucoidan as a stabilizer. Thereafter, fabricated nanocrystals (FPNC) were surface-modified with phospholipid to give lipid-coated nanocrystals (Lipo-NCs). Methods: The nanocrystals were fabricated by antisolvent crystallization followed by the probe sonication. The lipid coating was achieved by thin film hydration followed ultrasonic dispersion technique. Prepared nanocrystals were lyophilized to obtain a dry powder of FPNC and Lipo-NCs, used later for physicochemical, microscopic, and spectroscopic characterization to confirm the successful formation of desired nanocrystals. In-vitro and in-vivo investigations were also conducted to determine the role of nanocrystal powder in pulmonary drug delivery. Results: Lipo-NCs exhibited slower drug release, excellent flow properties, good aerosolization performance, higher drug distribution, and prolonged retention in the lungs compared to FPNC and pure PTX. Conclusion: Lipid-coated nanocrystals can be a novel formulation for the maximum localization of drugs in the lungs, thereby enhancing therapeutic effects and avoiding systemic side effects in lung cancer therapy. © 2024 Elsevier B.V.
Nanocarriers for tuberculosis therapy: Design of safe and effective drug delivery strategies to overcome the therapeutic challenges
(Editions de Sante, 2022) Kaushik Sarkar; Manish Kumar; Abhishek Jha; Kanchan Bharti; Mohana Das; Brahmeshwar Mishra
Tuberculosis (TB) is one of the most dreaded infectious diseases associated with a high mortality rate across the globe, especially in developing countries. Mycobacterium tuberculosis (M.tb), the bacteria causing the disease normally affects the lungs and causes pulmonary tuberculosis. However, it can also spread to other areas of the body and can cause secondary tuberculosis. Treatment of TB requires a high dosage of anti-tubercular drugs for a prolonged period. However, the main challenges associated with traditionally used drugs are poor aqueous drug solubility, low penetrability, systemic toxicity at effective doses, off-target accumulation, the mutation in the bacteria leading to multidrug-resistant strains, and lower bactericidal potential of the drug towards the bacteria in macrophages or deep infected tissues. In this context, nanomedicine has been identified to offer distinct advantages that can potentially address the aforementioned challenges. This review outlines the role of nanocarriers in overcoming the challenges associated with; drug solubility and permeation, the effect of reducing bacterial microenvironment on the free drug, and systemic toxicity of chemotherapeutics, etc. The review discusses the application of nanocarriers and their design to regulate the drug release, which ensures its concentration in therapeutic range for an extended duration, improves the efficacy of the drug, decreases the dosing frequency and dose. Also, the targetability of the payload delivery to the site of infection and cell-specific delivery, along with the role of pulmonary nanomedicine in localized and efficient delivery, which consequently reduces the toxicity and therapeutic dose of anti-tubercular drugs against pulmonary tuberculosis has also been discussed systematically. © 2021