Browsing by Author "Abhishesh Kumar Mehata"

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AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging
(Elsevier Ltd, 2024) Mahima Chauhan; Sonali; Saurabh Shekhar; Bhavna Yadav; Vandana Garg; Rohit Dutt; Abhishesh Kumar Mehata; Pooja Goswami; Biplob Koch; Madaswamy S. Muthu; Rahul Pratap Singh
Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies. © 2024 Elsevier B.V.
Bimetallic Au–Ag Nanoparticles: Advanced Nanotechnology for Tackling Antimicrobial Resistance
(MDPI, 2022) Chandrashekhar Singh; Abhishesh Kumar Mehata; Vishnu Priya; Ankit Kumar Malik; Aseem Setia; M. Nikitha Lakshmi Suseela; M. Nikitha Lakshmi Vikas; Patharaj Gokul; Patharaj Samridhi; Sanjeev K. Singh; Madaswamy S. Muthu
To date, there are no antimicrobial agents available in the market that have absolute control over the growing threat of bacterial strains. The increase in the production capacity of antibiotics and the growing antibacterial resistance of bacteria have majorly affected a variety of businesses and public health. Bimetallic nanoparticles (NPs) with two separate metals have been found to have stronger antibacterial potential than their monometallic versions. This enhanced antibacterial efficiency of bimetallic nanoparticles is due to the synergistic effect of their participating monometallic counterparts. To distinguish between bacteria and mammals, the existence of diverse metal transport systems and metalloproteins is necessary for the use of bimetallic Au–Ag NPs, just like any other metal NPs. Due to their very low toxicity toward human cells, these bimetallic NPs, particularly gold–silver NPs, might prove to be an effective weapon in the arsenal to beat emerging drug-resistant bacteria. The cellular mechanism of bimetallic nanoparticles for antibacterial activity consists of cell membrane degradation, disturbance in homeostasis, oxidative stress, and the production of reactive oxygen species. The synthesis of bimetallic nanoparticles can be performed by a bottom-up and top-down strategy. The bottom-up technique generally includes sol-gel, chemical vapor deposition, green synthesis, and co-precipitation methods, whereas the top-down technique includes the laser ablation method. This review highlights the key prospects of the cellular mechanism, synthesis process, and antibacterial capabilities against a wide range of bacteria. Additionally, we also discussed the role of Au–Ag NPs in the treatment of multidrug-resistant bacterial infection and wound healing. © 2022 by the authors.
Bioanalytical method development, in-vivo pharmacokinetic evaluation, ex-vivo platelet aggregation inhibition activity of a novel solid dispersion formulation of ticagrelor
(Frontiers Media SA, 2025) Abhishek Srivastava; Simrata Bedi; Abhishesh Kumar Mehata; Datta Maroti Pawde; Ketan Vinayakrao Hatware; Mohammad Ahmed Khan; Madaswamy Sona S Muthu; Uma Bhandari
Background: Ticagrelor, a potential antithrombotic drug indicated for cardiovascular events with acute coronary syndrome, has been restricted from its oral use due to poor aqueous solubility. The present investigation aimed to develop validated bioanalytical method for the analysis of plasma samples for improving the oral bioavailability of Ticagrelor. Additionally, evaluation of the improved antiplatelet activity of the Ticagrelor formulation compared to the marketed formulation. Methods: A bioanalytical method was developed in rat plasma samples using the isocratic separation mode. Plasma samples were processed by liquid-liquid extraction and analyzed by using reverse phase HPLC. A validated method was used for evaluating the pharmacokinetic profile of the developed formulation and marketed formulation in Sprague Dawley rats. Additionally, the ex-vivo antiplatelet aggregation activity was evaluated. Results: The developed method was accurate and linear (100 ng−800 ng) to quantify the drug in plasma. An in-vivo pharmacokinetic study was conducted for formulation at 10 mg/kg and different pharmacokinetic parameters were evaluated. From the results, we observed∼64% enhancements in the oral bioavailability of the Ticagrelor relative to the marketed formulation. The developed formulation (SD1) showed more significant inhibition of ADP-induced platelet aggregation compared to the marketed ticagrelor (RLD) formulation. Conclusion: In conclusion, we have successfully developed a validated analytical method for estimating Ticagrelor plasma concentration. Additionally, our study successfully enhanced Ticagrelor's oral bioavailability, and the developed formulation has more significant inhibition of ADP-induced platelet aggregation relative to the marketed formulation, indicating its substantial therapeutic potential. 2025 Srivastava, Bedi, Mehata, Pawde, Hatware, Khan, Muthu and Bhandari.
Bright fluorescent biocompatible Magnozyme nanoclusters for brain-cell in-vivo live imaging
(Elsevier B.V., 2025) Prachi Srivastava; Vivek Kumar Verma; Abhishesh Kumar Mehata; Mamata K. Singh; Shivesh Sabbarwal; Madaswamy Sona S Muthu; Biplob Koch; Manoj Kumar
Multifluorescent, water-dispersible magnesium nanoclusters (Magnozyme) were obtained using a simple and economical synthesis procedure. The prepared particles were 4 nm in size, and they exhibited significant emission at 450, 545, and 628 nm with multiple excitations of 366,469 and 560 nm wavelengths. The prepared particle exhibited a maximum absolute quantum yield of 21.3, 6.8 % and 5 % in red, green and blue spectrum, respectively, with excellent photostability, good ionic strength tolerability, and broad-range pH stability. The prepared Magnozyme demonstrates 95 % cell viability in human glioma brain cell lines (U-87 MG) and can be used as a probe for cellular imaging. Furthermore, imaging with this brain cell revealed significant cytoplasmic accumulation in the red, green, and blue regions. The confocal Z-stack study revealed the presence of Magnozyme at a depth of the cellular level by capturing a series of images at different planer axes (z-axis). Furthermore, In-vivo toxicity assessments and in-vivo imaging in mice revealed the nontoxicity behavior of Magnozyme with their great staining ability in physiological conditions, confirming their candidature toward biological cell imaging/labeling purposes. © 2025 Elsevier B.V.
Chitosan film of thiolated TPGS-modified Au-Ag nanoparticles for combating multidrug-resistant bacteria
(Elsevier B.V., 2024) Chandrashekhar Singh; Abhishesh Kumar Mehata; Matte Kasi Viswanadh; Punit Tiwari; Rajesh Saini; Sanjeev Kumar Singh; Ragini Tilak; Kavindra Nath Tiwari; Madaswamy S. Muthu
The widely used vitamin-E based amphiphilic material, tocopheryl polyethylene glycol succinate (TPGS) was further improvised to redox-sensitive thiolated TPGS (TPGS-SH), which has been achieved by attaching 4-aminothiophenol. Further, TPGS and TPGS-SH-coated bimetallic gold-silver nanoparticles (TPGS-Au-Ag-NP and TPGS-SH-Au-Ag-NP) were formulated to explore their antibacterial and wound healing abilities. The prepared NP were monodisperse with a mean hydrodynamic diameter of 69.5±3.23 nm, 59.65±3.23 nm, PDI of 0.3±0.05, 0.2±0.03 and a zeta potential of +29.2±2.71 mV and +35.28±1.53 mV, respectively. The TPGS and TPGS-SH modified Au-Ag-NP were tested for their antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli; minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) results showed that TPGS Au-Ag-NP, TPGS-SH-Au-Ag-NP displayed significantly stronger antibacterial activity than their coating material alone. The anti-efflux pump activity of the most potent antibacterial agent TPGS-SH-Au-Ag-NP was evaluated against MRSA. Toxicity assessment of TPGS-SH-Au-Ag-NP in human dermal fibroblasts showed 88% viability up to 125 µg/mL. The TPGS-SH-Au-Ag-NP, after incorporation in chitosan film (TPGS-SH-Au-Ag-NP-CS), exhibited sustained release and prolonged in vivo residence characteristics, which were evaluated by IVIS. Results also revealed that treatment with TPGS-SH-Au-Ag-NP showed a significant 87% wound healing rate after 12 days of application in the rat model. Hence, we concluded that TPGS-SH-Au-Ag-NP was safe and effective against test bacteria MRSA and capable of efficient wound healing when incorporated in chitosan film. © 2024 Elsevier B.V.
Chitosan nanoplatform for the co-delivery of palbociclib and ultra-small magnesium nanoclusters: dual receptor targeting, therapy and imaging
(Ivyspring International Publisher, 2024) Abhishesh Kumar Mehata; Virendra Singh; Vikas; Prachi Srivastava; Biplob Koch; Manoj Kumar; Madaswamy S. Muthu
Theranostic nanoparticles have gained significant attention in cancer diagnosis and therapy. In this study, estrone (ES) and folic acid (FA) functionalized single and dual receptor targeted theranostic chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were loaded with palbociclib (PB) and ultra-small magnesium nanoclusters (UMN). The developed nontargeted theranostic NPs (PB-UMN-CS-NPs), estrogen receptor targeted theranostic NPs (PB-UMN-CS-ES-NPs), folate receptor targeted theranostic NPs (PB-UMN-CS-FA-NPs), and dual targeted theranostic NPs (PB-UMN-CS-ES-FA-NPs) have particle sizes of 178.4 ± 1.21 nm, 181.6± 1.35 nm, 185.1± 1.33 nm, and 198.2± 1.43 nm with surface charges of +19.02± 0.382 mV, +13.89±0.410 mV, +16.72±0.527 mV and +15.23±0.377 mV, respectively. Cytotoxicity studies on estrogen receptor (ER) and folate receptor (FR) expressing breast cancer cells revealed that dual-targeted theranostic NPs (PB-UMN-CS-FA-ES-NPs) were more effective, inhibiting cell growth by 54.17 and 42.23 times in MCF-7 and T-47D cells compared to free PB, respectively. Additionally, developed NPs were capable of inhibiting the cell cycle progression of MCF-7 cells from the G1 phase to the S phase more efficiently compared to free PB. Ultrasound and photoacoustic (USG/PA) imaging demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs. Moreover, in vivo optical imaging demonstrated tumor specific accumulation of the dual-targeted theranostic NPs. Furthermore, in vitro hemocompatibility and histopathological studies confirmed the biocompatibility of developed nanoformulations. © The author(s).
Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging
(American Chemical Society, 2023) Abhishesh Kumar Mehata; Virendra Singh; None Vikas; Nitesh Singh; Abhijit Mandal; Debabrata Dash; Biplob Koch; Madaswamy S. Muthu
Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34- and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2-3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use. © 2023 American Chemical Society.
Comparative evaluation of liquid-liquid extraction and nanosorbent extraction for HPLC-PDA analysis of cabazitaxel from rat plasma
(Elsevier B.V., 2024) Medapati Nikitha Lakshmi Suseela; Abhishesh Kumar Mehata; Bhaskar Vallamkonda; Pathraj Gokul; Aditi Pradhan; Jyotsana Pandey; Joseph Selvin; M. Sterlin Leo Hudson; Madaswamy S. Muthu
A precise, sensitive, accurate, and validated reverse-phase high-performance liquid chromatography (RP-HPLC) method with a bioanalytical approach was utilized to analyze Cabazitaxel (CBZ) in rat plasma. Comparative research on extraction recoveries was performed between traditional liquid-liquid extraction (LLE) and synthesized graphene oxide (GO) based magnetic solid phase extraction (GO@MSPE). The superparamagnetic hybrid nanosorbent was synthesized using the combination of iron oxide and GO and subsequently applied for extraction and bioanalytical quantification of CBZ from plasma by (HPLC-PDA) analysis. Fourier- transform infrared spectroscopy (FT-IR), particle size, scanning electron microscopy (SEM), and x-ray diffraction (XRD) analysis were employed in the characterization of synthesized GO@MSPE nanosorbent. The investigation was accomplished using a shim pack C18 column (150 mm×4.6 mm, 5 µm) with a binary gradient mobile phase consisting of formic acid: acetonitrile: water (0.1:75:25, v/v/v) at a 0.8 mL/min flow rate, and a λmax of 229 nm. The limits of detection (LOD) and quantitation (LOQ) have been determined to be 50 and 100 ng/mL for both LLE and SPE techniques. The linearity range of the approach encompassed from 100 to 5000 ng/mL and was found to be linear (coefficient of determination > 0.99) for CBZ. The proposed method showed extraction recovery of 76.8–88.4% for the synthesized GO@MSPE and 69.3–77.4% for LLE, suggesting that the proposed bioanalytical approach was robust and qualified for all validation parameters within the acceptable criteria. Furthermore, the developed hybrid GO@MSPE nanosorbent with the help of the proposed RP-HPLC method, showed a significant potential for the extraction of CBZ in bioanalysis. © 2024 Elsevier B.V.
Corrigendum to “Nanofibers of N,N,N-trimethyl chitosan capped bimetallic nanoparticles: Preparation, characterization, wound dressing and in vivo treatment of MDR microbial infection and tracking by optical and photoacoustic imaging” [Int. J. Biol. Macromol. 263 (2024) 130154](S0141813024009577)(10.1016/j.ijbiomac.2024.130154)
(Elsevier B.V., 2024) Ankit Kumar Malik; Chandrashekhar Singh; Abhishesh Kumar Mehata; Vikas; Aseem Setia; Madaswamy S. Muthu; Punit Tiwari; Dipti Verma; Ashim Mukherjee
The authors regret a mistake, which was entirely unintentional and occurred during the final stages of figure preparation. Specifically, during the data consolidation and visualization process, due to a labelling mistake in our repository of the same animal group, the 7B Untreated Day 4 images were mistakenly over-copied in the 7B Untreated Day 12 folder and the experimental results for Untreated Day 12 was inadvertently selected. Despite our thorough review processes though typically rigorous, we failed to catch this error by our naked eyes due to the compressed timeframe and multiple concurrent reviews. We have prepared a corrected version of Fig. 7B Untreated Day 12 which accurately reflects our findings and data discussed in the article, whereas the 7B Untreated Day 4 data is correct.[Formula presented] Fig. 7: (B) Skin histological studied under brightfield microscope (at 100× magnification) 4th day, 8th day and 12th day. The authors would like to apologise for any inconvenience caused. © 2024 Elsevier B.V.
Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders
(American Chemical Society, 2023) Aseem Setia; Abhishesh Kumar Mehata; Vishnu Priya; Datta Maroti Pawde; Dharmendra Jain; Sanjeev Kumar Mahto; Madaswamy S. Muthu
Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents. © 2023 American Chemical Society.
Design of novel bioadhesive chitosan film loaded with bimetallic gold-silver nanoparticles for antibiofilm and wound healing activity
(Institute of Physics, 2023) Chandrashekhar Singh; Abhishesh Kumar Mehata; Vikas; Punit Tiwari; Aseem Setia; Ankit Kumar Malik; Sanjeev K Singh; Ragini Tilak; Madaswamy S Muthu
Microbial infections and antibiotic resistance are among the leading causes of morbidity and mortality worldwide. The bimetallic chitosan (CS)-capped gold-silver nanoparticles (CS-AuAg-NPs) were prepared by the seeded growth synthesis technique. The nanoparticles were optimized for particle size (PS), zeta potential (ZP) and antibacterial activity by Box-Behnken design at three levels and three factors. The developed CS-AuAg-NPs were polydispersed with mean hydrodynamic PS in the range of 55 - 289 nm and ZP ranges from +8.53 mV to +38.6 mV. The optimized CS-AuAg-NPs found to have a minimum inhibitory concentration and minimal bactericidal concentration of 1.625 ± 0.68 and 3.25 ± 0.74 µg ml−1 towards multidrug resistant (MDR) Staphylococcus aureus ATCC 25923 (MDR AT) and 3.25 ± 0.93 and 3.25 ± 0.86 µg ml−1 towards MDR S. aureus clinical isolate MDR1695 (MDR CI) strain, respectively. The CS-AuAg-NPs were much more effective against MDR AT and MDR CI compared to clindamycin standard. The live/dead assay of clinical isolates strain demonstrated significant reduction of bacterial cells ∼67.52 folds compared to control group in 12 h. The hemolysis study suggested that CS-AuAg-NPs were non-hemolytic and safer for application in the wound. Furthermore, CS-AuAg-NPs were distributed in the CS film, which showed 87% wound recovery after 7 d in mice model. Hence, we concluded that CS-AuAg-NPs was safer and more effective against MDR bacteria and capable of skin regeneration in the infected wound. © 2023 IOP Publishing Ltd
Development and characterization of micelles for nucleolin-targeted co-delivery of docetaxel and upconversion nanoparticles for theranostic applications in brain cancer therapy
(Editions de Sante, 2023) Mahima Chauhan; Rahul Pratap Singh; Sonali; Bhavna Yadav; Saurabh Shekhar; Abhitinder Kumar; Abhishesh Kumar Mehata; Amit Kumar Nayak; Rohit Dutt; Vandana Garg; Vikas Kailashiya; Madaswamy S. Muthu; Biplob Koch; Dharmendra Kumar Pandey
Despite the existence of several treatment modalities and advancements in cancer research, brain cancer is still incurable. Over-expression of nucleolin receptors on cancer cells has been explored in several studies. The study aimed to develop and characterize nucleolar -targeted theranostic pluronic F127-TPGS micelles for brain cancer therapy. The theranostic agents i.e., Docetaxel; DTX as a therapeutic agent, and the upconversion nanoparticles; UCNP as a diagnostic agent, were loaded into micelles by a slightly-modified solvent casting method. Micelles were further decorated with synthesized TPGS-AS1411 aptamer conjugate for targeting brain cancer cells. The prepared micelles were found between 90 and 165 nm, with a uniform homogeneous and narrow distribution in formulations. DTX and UCNP encapsulation efficiencies of micelles were found 74–88% and 38–40%, respectively. Micelles have depicted sustained release of DTX for as long as 72 h. Hemolytic assay confirmed that DUTP-AS1411 aptamer micelles were found more biocompatible than Taxotere®. The cytotoxicity results revealed that DTP, DUTP, and DUTP-AS1411 aptamer micelles achieved 4.20, 11.70, and 17.54-fold more effectiveness than Taxotere®, after 24 h of therapy, respectively. In addition, DUTP-AS1411 aptamer micelles achieved higher tmax and Cmax of DTX up to 8- and 1.5-fold, respectively, compared to Taxotere® treated group. A similar trend was observed for the brain-distribution study as DUTP-AS1411 aptamer micelles were found more efficacious than Taxotere®. The histopathology studies showed no toxicity and cellular damage even after the 14th and 28th day post i.v. administration of normal saline, DTP, DUTP, and DUTP-AS1411 aptamer micelles formulations whereas Taxotere® has reported to cause toxicity in brain tissues. The study revealed that DUTP-AS1411 aptamer micelles inherit promising and improved therapeutic efficacy, reduced toxicity, dosing frequency, and sustained drug release behavior which can be further exploited as a potential therapeutic approach for brain cancer. © 2023 Elsevier B.V.
Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer
(Elsevier B.V., 2023) Mahima Chauhan; Rahul Pratap Singh; Sonali; Bhavna Yadav; Saurabh Shekhar; Lokesh Kumar; Abhishesh Kumar Mehata; Vikas Jhawat; Rohit Dutt; Vandana Garg; Vikas Kailashiya; Madaswamy S. Muthu
Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90–170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from − 1.5 ± 0.02 to − 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22–79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18–58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 μg/ml compared to Taxotere® (2.73 ± 0.73 μg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 μg.h/ml higher than Taxotere® (14.14 ± 10.59 μg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients. © 2023 Elsevier B.V.
Efficient delivery of abciximab using mesoporous silica nanoparticles: In-vitro assessment for targeted and improved antithrombotic activity
(Elsevier B.V., 2022) Vishnu Priya; Vikas; Abhishesh Kumar Mehata; Dharmendra Jain; Sanjeev K. Singh; Madaswamy S. Muthu
Abciximab (ABX) is a chimeric monoclonal antibody reported for antithrombotic activity but their delivery remains challenging due to its poor stability in a biological system. The purpose of this research was to deliver ABX on the target efficiently using mesoporous silica nanoparticles (MSN). ABX coated mesoporous silica nanoparticles (MSN-ABX) were formulated and analyzed for particle size, shape, zeta-potential, surface morphology and surface chemistry. XPS analysis confirmed the presence of ABX on the surface of amino functionalized mesoporous silica nanoparticles (MSN-NH2). The degree of ABX attachment was 67.53 ± 5.81 % which was demonstrated by the Bradford assay. Furthermore, the targeting efficiency of the targeted nanoparticles has been evaluated by capturing the fluorescent images in-vitro which showed the significant accumulation of the ABX coated nanoparticles towards activated platelets. The significant (P < 0.05) increase in affinity of DiD dye loaded nanoparticles towards the activated platelets was confirmed by using an in-vitro imaging through photon imager optima. The hemolysis study of the nanoparticle formulations revealed that they were non-hemolytic for healthy human blood. The in-vitro antithrombotic effects of MSN-ABX were observed by blood clot assay which revealed its superior antithrombotic activity over clinical injection of ABX and could be a promising carrier for improved ABX targeted delivery. © 2022 Elsevier B.V.
Exosomes as a novel nanomedicine platform for personalized triple-negative breast cancer therapy
(Newlands Press Ltd, 2023) Abhishesh Kumar Mehata; Niharika Gupta; Madaswamy S Muthu
[No abstract available]
Exosomes fused liposomes: formulation, stability studies and theranostic evaluation for breast cancer applications
(Elsevier B.V., 2025) Nidhi Verma; Rupen Tamang; Abhishesh Kumar Mehata; Aseem Setia; Biplob Koch; Madaswamy Sona S Muthu
This study presents exosomes fused liposomes vesicles as a multifunctional nanocarriers for breast cancer theranostics. Exosomes isolation from human plasma using polyethylene glycol (PEG) precipitation is an efficient and cost-effective method that preserves vesicle integrity. These exosomes were fused with liposomes to enhance drug loading, stability, and tumor-targeting. The PLB-EXO-LIPO-VCs and MB-EXO-ICG-LIPO-VCs fused vesicles showed particle sizes of 194.5 ± 2.8 nm and 175.0 ± 2.1 nm, PDI values of 0.234 ± 0.01 and 0.225 ± 0.02, and zeta potentials of − 30.31 ± 0.05 mV and − 28.33 ± 0.04 mV, respectively. TEM, SEM, and SPM confirmed a spherical morphology with smooth membranes, and FTIR analysis validated membrane fusion, with retention of exosomal components. The PLB-EXO-LIPO-VCs exhibited encapsulation efficiency and drug loading (EE/DL) of 86.78 ± 0.05 % and 22.01 ± 0.02 %, while EE/DL of MB-EXO-ICG-LIPO-VCs showed 94.06 %/27.45 % for ICG and 78.91 %/20.23 % for MB. The vesicles demonstrated pH-responsive, sustained drug release governed by anomalous (non-Fickian) diffusion. The fused vesicles showed superior stability at 25 °C, 4 °C, and −20 °C. Furthermore, PLB-EXO-LIPO-VCs exhibited 19.53-fold higher cytotoxicity than free PLB, accompanied by increased cellular uptake, ROS generation, and mitochondria-mediated apoptosis. Safety of the vesicles was confirmed by haematological, biochemical, haemolysis, and histopathological evaluations. In vivo imaging revealed tumor-specific accumulation and significant reduction in tumor volume, hypoxia, and angiogenesis in DMBA-induced breast tumors, highlighting their potential in breast cancer diagnostic and therapeutic applications. © 2025 Elsevier B.V.
Fluorescent Calcium Nanocluster-Driven Theranostic Nanoplatforms for Advanced Imaging and Therapy in Breast Tumor
(American Chemical Society, 2025) Abhishesh Kumar Mehata; Vivek Kumar Verma; Virendra Pratap Singh; Aseem Setia; None Vikas; Matte Kasi Viswanadh; Shivesh Sabbarwal; Manoj Kumar; Biplob Koch; Madaswamy Sona S Muthu
Biocompatible CaCO3 nanoclusters were prepared by using a simple biomineralization technique. Employing CaCO3 nanoclusters in breast cancer treatment provides an exciting avenue for theranostics, which merges precise imaging with individualized treatment plans. They were highly suitable for improving the efficacy and precision of breast cancer detection and therapy with minimal adverse effects due to their biocompatibility, controlled drug release, pH sensitivity, and adaptability. In our current study, we proposed a palbociclib (PBB)-loaded fluorescent calcium nanocluster-based redox-sensitive drug delivery system for efficient breast cancer imaging and therapy. The developed nanoparticles were analyzed for their morphology and various physicochemical properties. The particle sizes of the formulated FNC-PBB-CS-NPs (nonredox-sensitive) and FNC-PBB-CS-SS-NPs (redox-sensitive) nanoparticles were 150.2 ± 2.1 and 160.4 ± 1.4 nm, respectively. The zeta potential of nonredox-sensitive nanoparticles was measured to be +17.12 ± 1.34 mV, while the zeta potential of redox-sensitive nanoparticles was +14.32 ± 1.17 mV. The entrapment efficiencies of FNC-PBB-CS-NPs and FNC-PBB-CS-SS-NPs were determined to be 88.74 ± 2.34 and 89.26 ± 1.21%, respectively. FNC-PBB-CS-SS-NPs demonstrated quicker drug release at acidic pH compared to FNC-PBB-CS-NPs. The cytotoxicity assay conducted on MCF-7 and T-47D cells indicated that FNC-PBB-CS-NPs and FNC-PBB-CS-SS-NPs exhibited greater cytotoxicities than free PBB. Furthermore, the Hoechst/PI dual-staining experiment demonstrated the superior activity of FNC-PBB-CS-SS-NPs over FNC-PBB-CS-NPs and free PBB. Ultrasound/photoacoustic imaging revealed that FNC-PBB-CS-SS-NPs effectively reduced tumor size, hypoxic tumor regions, and tumor vascularity compared to FNC-PBB-CS-NPs and free PBB. Additionally, in vivo optical imaging showed that the FNC-PBB-CS-SS-NPs accumulated more specifically in tumors than the other formulations. © 2025 American Chemical Society.
Formulation and in vitro evaluation of upconversion nanoparticle-loaded liposomes for brain cancer
(Newlands Press Ltd, 2020) Narendra; Abhishesh Kumar Mehata; Matte Kasi Viswanadh; Roshan Sonkar; Datta Maroti Pawde; Vishnu Priya; Mamata Singh; Biplob Koch; Madaswamy S Muthu
Aim: This work focused on the development of transferrin-conjugated theranostic liposomes consisting of docetaxel (DXL) and upconversion nanoparticles for the diagnosis and treatment of gliomas. Materials & methods: Upconversion nanoparticles and docetaxel-loaded theranostic liposomes were prepared by a solvent injection method. Formulations were analyzed for physicochemical properties, encapsulation efficiency, drug release, elemental analysis, cytotoxicity and fluorescence. Results: The particle size was around 200 nm with spherical morphology and an encapsulation efficiency of up to 75.93%, was achieved for liposomes with an in vitro drug release of 71.10%. The IC50 values demonstrated enhanced cytotoxicity on C6 glioma cells with targeted liposomes in comparison with nontargeted liposomes. Conclusion: Prepared theranostic liposomes may be promising for clinical validation after an in vitro and in vivo evaluation on cell lines and animals, respectively. © 2020 Future Medicine Ltd.. All rights reserved.
GPIIb/IIIa Receptor Targeted Rutin Loaded Liposomes for Site-Specific Antithrombotic Effect
(American Chemical Society, 2023) Vishnu Priya; Sanjeev K. Singh; Ravindran Revand; Sandip Kumar; Abhishesh Kumar Mehata; Paulraj Sushmitha; Sanjeev Kumar Mahto; Madaswamy S. Muthu
Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use. © 2023 American Chemical Society. All rights reserved.
Luliconazole Nail Lacquer for the Treatment of Onychomycosis: Formulation, Characterization and In Vitro and Ex Vivo Evaluation
(Springer Science and Business Media Deutschland GmbH, 2022) Deepa Dehari; Abhishesh Kumar Mehata; Vishnu Priya; Dharmnath Parbat; Deepak Kumar; Anand Kumar Srivastava; Sanjay Singh; Ashish Kumar Agrawal
Onychomycosis is the most common fungal infection of the nail affecting the skin under the fingertips and the toes. Currently, available therapy for onychomycosis includes oral and topical therapies, either alone or in combination. Oral antifungal medication has been associated with poor drug bioavailability and potential gastrointestinal and systemic side effects. The objective of this study was to prepare and evaluate the luliconazole nail lacquer (LCZ-NL) for the effective treatment of onychomycosis. In the current work, LCZ-NL was formulated in combination with penetration enhancers to overcome poor penetration. A 32 full factorial formulation design of experiment (DOE) was applied for optimization of batches with consideration of dependent (drying time, viscosity, and rate of drug diffusion) and independent (solvent ratio and film former ratio) variables. The optimized formulation was selected based on drying time, viscosity, and rate of drug diffusion. The optimized formulation was further evaluated for % non-volatile content assay, smoothness of flow, water resistance, drug content, scanning electron microscope (SEM), atomic force microscope (AFM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), in vitro drug release, ex vivo transungual permeation, antifungal efficacy, and stability study. The optimized LCZ-NL contained 70:30 solvent ratio and 1:1 film former ratio and was found to have ~ 1.79-fold higher rate of drug diffusion in comparison with LULY™. DSC and XRD studies confirmed that luliconazole retains its crystalline property in the prepared formulation. Antifungal study against Trichophyton spp. showed that LCZ-NL has comparatively higher growth inhibition than LULY™. Hence, developed LCZ-NL can be a promising topical drug delivery system for treating onychomycosis. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.