BHU Institutional Repository :: Browsing by Author "Mehata A.K."

Browsing by Author "Mehata A.K."

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AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging
(Elsevier Ltd, 2024) Chauhan M.; Sonali; Shekhar S.; Yadav B.; Garg V.; Dutt R.; Mehata A.K.; Goswami P.; Koch B.; Muthu M.S.; Singh R.P.
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.
Chitosan film of thiolated TPGS-modified Au-Ag nanoparticles for combating multidrug-resistant bacteria
(Elsevier B.V., 2024) Singh C.; Mehata A.K.; Viswanadh M.K.; Tiwari P.; Saini R.; Singh S.K.; Tilak R.; Tiwari K.N.; Muthu M.S.
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 �g/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) Mehata A.K.; Singh V.; Vikas; Srivastava P.; Koch B.; Kumar M.; Muthu M.S.
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).
Comparative evaluation of liquid-liquid extraction and nanosorbent extraction for HPLC-PDA analysis of cabazitaxel from rat plasma
(Elsevier B.V., 2024) Suseela M.N.L.; Mehata A.K.; Vallamkonda B.; Gokul P.; Pradhan A.; Pandey J.; Selvin J.; Sterlin Leo Hudson M.; Muthu M.S.
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 �m) 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 ?max 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) Malik A.K.; Singh C.; Mehata A.K.; Vikas; Setia A.; Muthu M.S.; Tiwari P.; Verma D.; Mukherjee A.
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.
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
(Elsevier B.V., 2024) Malik A.K.; Singh C.; Tiwari P.; Verma D.; Mehata A.K.; Vikas; Setia A.; Mukherjee A.; Muthu M.S.
Recent advancements in wound care have led to the development of interactive wound dressings utilizing nanotechnology, aimed at enhancing healing and combating bacterial infections while adhering to established protocols. Our novel wound dressings consist of N,N,N-trimethyl chitosan capped gold?silver nanoparticles (Au-Ag-TMC-NPs), with a mean size of 108.3 � 8.4 nm and a zeta potential of +54.4 � 1.8 mV. These optimized nanoparticles exhibit potent antibacterial and antifungal properties, with minimum inhibitory concentrations ranging from 0.390 ?g ml?1 to 3.125 ?g ml?1 and also exhibited promising zones of inhibition against multi-drug resistant strains of S. aureus, E. coli, P. aeruginosa, and C. albicans. Microbial transmission electron microscopy reveals substantial damage to cell walls and DNA condensation post-treatment. Furthermore, the nanoparticles demonstrate remarkable inhibition of microbial efflux pumps and are non-hemolytic in human blood. Incorporated into polyvinyl alcohol/chitosan nanofibers, they form Au-Ag-TMC-NPs-NFs with diameters of 100�350 nm, facilitating efficient antimicrobial wound dressing. In vivo studies on MDR microbial-infected wounds in mice showed 99.34 % wound healing rate within 12 days, corroborated by analyses of wound marker protein expression levels and advanced imaging techniques such as ultrasound/photoacoustic imaging, providing real-time visualization and blood flow assessment for a comprehensive understanding of the dynamic wound healing processes. � 2024 Elsevier B.V.
PLGA Nanoplatform for the Hypoxic Tumor Delivery: Folate Targeting, Therapy, and Ultrasound/Photoacoustic Imaging
(American Chemical Society, 2024) Mehata A.K.; Bonlawar J.; Tamang R.; Malik A.K.; Setia A.; Kumar S.; Challa R.R.; Vallamkonda B.; Koch B.; Muthu M.S.
Effective targeting of breast tumors is critical for improving therapeutic outcomes in breast cancer treatment. Additionally, hypoxic breast cancers are difficult to treat due to resistance toward chemotherapeutics, poor vascularity, and enhanced angiogenesis, which complicate effective drug delivery and therapeutic response. Addressing this formidable challenge requires designing a drug delivery system capable of targeted delivery of the anticancer agent, inhibition of efflux pump, and suppression of the tumor angiogenesis. Here, we have introduced Palbociclib (PCB)-loaded PLGA nanoparticles (NPs) consisting of chitosan-folate (CS-FOL) for folate receptor-targeted breast cancer therapy. The developed NPs were below 219 nm with a smooth, spherical surface shape. The entrapment efficiencies of NPs were achieved up to 85.78 � 1.8%. Targeted NPs demonstrated faster drug release at pH 5.5, which potentiated the therapeutic efficacy of NPs due to the acidic microenvironment of breast cancer. In vitro cellular uptake study in MCF-7 cells confirmed the receptor-mediated endocytosis of targeted NPs. In vivo ultrasound and photoacoustic imaging studies on rats with hypoxic breast cancer showed that targeted NPs significantly reduced tumor growth and hypoxic tumor volume, and suppressed angiogenesis. � 2024 American Chemical Society.
Polyvinyl alcohol-chitosan based oleanolic acid nanofibers against bacterial infection: In vitro studies and in vivo evaluation by optical and laser Doppler imaging modalities
(Elsevier B.V., 2024) Badgujar P.; Malik A.K.; Mehata A.K.; Setia A.; Verma N.; Randhave N.; Shukla V.N.; Kande V.; Singh P.; Tiwari P.; Mahto S.K.; Muthu M.S.
The present work focuses on the fabrication of polyvinyl alcohol-chitosan-loaded oleanolic acid-nanofibers (PVA-CS-OLA-NFs) for bacterial infection. The prepared PVA-CS-OLA-NFs were characterized for contact angle, SEM, AFM, XRD, FTIR, and TGA. The solid-state characterization and in vitro performance evaluation of nanofibers reveal consistent interconnection and diameters ranging from 102 � 9.5 to 386 � 11.6 nm. The nanofibers have a flat surface topography and exhibit efficient drug entrapment. Moreover, the in vitro release profile of PVA-CS-OLA-NFs was found to be 51.82 � 1.49 % at 24 h. Furthermore, the hemocompatibility study showed that the developed PVA-CS-OLA-NFs are non-hemolytic to human blood. The PVA-CS-OLA-NFs demonstrate remarkable antibacterial capabilities, as evidenced by their MBC and MIC values, which range from 128 and 32 ?g/mL, against the strains of S. aureus. The in-vivo fluorescence optical imaging showed the sustained PVA-CS-OLA-NFs release at the wound site infected with S. aureus for a longer duration of time. Moreover, the PVA-CS-OLA-NFs showed superior wound healing performance against S. aureus infected wounds compared to the marketed formulation. Further, the laser Doppler imaging system improved oxygen saturation, blood supply, and wound healing by providing real-time blood flow and oxygen saturation information. � 2024 Elsevier B.V.
Premna integrifolia: A Review on the Exploration of its Potential Pharmacological and Therapeutic Properties
(Bentham Science Publishers, 2024) Singh C.; Mehata A.K.; Muthu M.S.; Tiwari K.N.
Several Premna species can be found over the entire tropical and subtropical regions of Australia, Asia, and Africa. Many conventional herbal preparations using P. integrifolia (Lamiaceae) have been reported for their potential health advantages. The P. integrifolia is taxonomically ambiguous because of the wide variation in specimens obtained from various geographic locations. The plant is extensively used to treat immune-related disorders, skin conditions, inflammatory conditions, and stomach issues. The root of P. integrifolia is broadly utilized in the manufacture of Ayurvedic pharmaceutical products, such as Dasamula Kvatha and Chayawanprash Avaleha. It has also been identified to have antibacterial, hepatoprotective, and antifungal properties. The current study aims to investigate the antioxidant and cytotoxic activity of P. integrifolia against various cancers, as well as its antiinflammatory activity, antidiabetic, cardiac-stimulant, anti-obesity, hepatoprotective, immunomodulatory, analgesic, antiarthritic, antiparasitic, and wound healing activity, as well as the presence of various secondary metabolites in different parts of the plant used in a variety of formulations. � 2024 Bentham Science Publishers.
PTSA-induced synthesis, in silico and nano study of novel ethylquinolin�thiazolo�triazole in cervical cancer
(Taylor and Francis Ltd., 2024) Sonker P.; Tamang R.; Mehata A.K.; Nidhar M.; Sharma V.P.; Kumar V.; Muthu M.S.; Koch B.; Tewari A.K.
Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin�thiazolo�triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin�thiazolo�triazole was carried out with D-?-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer. � 2024 Expert Publishing Science Ltd trading as Taylor & Francis.
Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy
(American Chemical Society, 2024) Dhamija P.; Mehata A.K.; Tamang R.; Bonlawar J.; Vaishali N.; Malik A.K.; Setia A.; Kumar S.; Challa R.R.; Koch B.; Muthu M.S.
Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 � 1.8 nm and 193.7 � 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 � 2.67 mV and +9.095 � 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 � 1.29% and 87.72 � 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs. � 2024 American Chemical Society.

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