Browsing by Author "Abhishek Jha"

Now showing 1 - 13 of 13

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.
Enhanced in vitro therapeutic efficacy of triphenyltin (IV) loaded vitamin E TPGS against breast cancer therapy
(Elsevier Ltd, 2022) Mamata Singh; Nishant Kumar Rana; Madaswamy S. Muthu; Abhishek Jha; Tushar S. Basu Baul; Biplob Koch
Triphenyltin (Ph3SnL (IV) is a synthetic hydrophobic compound functionalized with a diazo and amino group having potentials to use in anticancer chemotherapy, but its hydrophobic property hindrance the therapeutic efficacy for wider use against cancer treatment. Therefore, in our present work we aimed to develop TPGS micelles loaded with Ph3SnL (IV) to enhanced the therapeutic efficacy in breast cancer cells as compare to docetaxel. Solvent casting method was employed to develop TPGS-Ph3SnL1 (IV), TPGS-Ph3SnL5 (IV) and TPGS-DTX micelles to increase the aqueous solubility of hydrophobic drugs. The size of TPGS-Ph3SnL1 (TSD-30-F) and TPGS-Ph3SnL5 (TSD-34-F) micelles were initially evaluated by dynamic light scattering which were found to be below 50 nm. The morphological characteristics of micelles were observed by TEM, SEM and AFM respectively. Further, drug encapsulation and in vitro drug release profiles of micelles were assessed using dialysis bag diffusion technique under sink condition at pH7.4 at 37 °C over 72 h and analysed through UV–visible spectrophotometry. The anticancer efficacy of TSD-30-F, TSD-34-F and DTX-F were tested against two breast cancer cell lines (MCF-7 and MDA-MB-231) and cervical cancer cell line (HeLa) by MTT assay. IC50 values of TSD-30-F and TSD-34-F displayed very high activity towards breast cancer cells as compared to DTX-F, while moderate in case of HeLa cells. Acridine orange/ethidium bromide as well as flow cytometry observation delineates that micelles induced apoptotic mode of cell death after elevating intracellular reactive oxygen level. Higher cellular uptake of micelles in breast cancer cells was evaluated through TPGS-coumarin6 as compared to coumarin6 without TPGS. Therefore, our study suggests that TPGS micelles may increase therapeutics efficacy of Ph3SnL (IV) in breast cancer cells and can be a promising candidate for targeted drug delivery against breast cancer cells. © 2022 Elsevier Ltd
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.
Gold liposomes for brain-targeted drug delivery: Formulation and brain distribution kinetics
(Elsevier Ltd, 2021) Roshan Sonkar; Sonali; Abhishek Jha; Matte Kasi Viswanadh; Ankita Sanjay Burande; Narendra; Datta Maroti Pawde; Krishna Kumar Patel; Mamata Singh; Biplob Koch; Madaswamy S. Muthu
This work was aimed to formulate transferrin (Tf) receptor targeted gold based theranostic liposomes which contain both docetaxel (DCX) and glutathione reduced gold nanoparticles (AuGSH) for brain-targeted drug delivery and imaging. AuGSH was prepared by reducing chloroauric acid salt using glutathione. The co-loading of DCX and AuGSH into liposomes was achieved by the solvent injection technique, and Tf was post-conjugated on the surface of the liposomes using carboxylated Vit-E TPGS (TPGS-COOH) as a linker. The liposomes were characterized for various parameters such as size, shape, surface charge, and drug release. The Tf receptor targeted gold liposomes were evaluated for the cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based colorimetric assay and in-vitro qualitative cellular uptake studies using confocal microscopy. The in-vivo site specific delivery of DCX was analyzed by the brain distribution study of DCX in comparison with marketed formulation (Docel™). A sustained drug release of about 70% was observed from liposomes in the span of 72 h. The in-vivo results demonstrated that targeted gold liposomes were able to deliver DCX into the brain by 3.70, 2.74 and 4.08-folds higher than Docel™ after 30, 120 and 240 min of the treatment, respectively. Besides, the results of these studies have suggested the feasibility of Tf decorated AuGSH and DCX co-loaded liposomes as a promising platform for targeted nano-theranostics. © 2020 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
Polymeric nanosystems for cancer theranostics
(Elsevier, 2023) Manish Kumar; Abhishek Jha; Brahmeshwar Mishra
Polymeric nanocarriers loaded with the anticancer drug have been identified as promising methods for effective cancer therapy. Polymeric nanoparticles owe unique features like high water solubility, biodegradability, biocompatibility, nontoxicity, surface functionalization potential, and stability, therefore, can be utilized for the design of a safe anticancer theranostic nanomedicine. Several polymeric platforms are reported in this context, including nanospheres, micelles, conjugates, nanogels, scaffolds, dendrimers, etc. These may be loaded with both, contrast agents and anticancer biomolecules for the preparation of theranostic nano polymeric carrier. These theranostic systems provide dual functionalities of therapeutics delivery for anticancer effect and imaging function for real-time monitoring of drug distribution and therapeutic action assessment at the target site. Besides, polymeric nanocarriers could be further modified with receptor-targeted and stimuli-responsive moieties for providing both; tumor-targeted imaging and targeted cancer therapy. This chapter reports various polymeric nanoparticles that can be used for targeted delivery and site-specific imaging of tumors for providing imaging-guided cancer therapy. Polymeric nanoparticles can be equipped with one or more imaging agents for providing uni, dual or multimodal imaging. It offers a potential platform to merge chemo/photothermal/photodynamic therapy with one or more imaging techniques namely; photoacoustic imaging, magnetic resonance imaging, ultrasound imaging, positron emission tomography, single-photon emission computed tomography, and other optical imaging. © 2023 Elsevier Inc. All rights reserved.