Browsing by Author "Madaswamy S. Muthu"

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Antipsychotic nanomedicine: A successful platform for clinical use
(Future Medicine Ltd., 2014) Madaswamy S. Muthu; Poornima Agrawal; Rahul Pratap Singh
[No abstract available]
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.
Bioadhesive micelles of D-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery
(Elsevier B.V., 2017) Poornima Agrawal; Sonali; Rahul Pratap Singh; Gunjan Sharma; Abhishesh K. Mehata; Sanjay Singh; Chellapa V. Rajesh; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this work was to prepare targeted bioadhesive D-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50 values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24 h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48 h of treatments, respectively. © 2017 Elsevier B.V.
Challenges posed by the scale-up of nanomedicines
(2012) Madaswamy S. Muthu; Barnabas Wilson
[No abstract available]
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-folate decorated carbon nanotubes for site specific lung cancer delivery
(Elsevier Ltd, 2017) Rahul Pratap Singh; Gunjan Sharma; Sonali; Sanjay Singh; Shreekant Bharti; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this work was to formulate chitosan-folate conjugated multi-walled carbon nanotubes for the lung cancer targeted delivery of docetaxel. The chitosan-folate conjugate was synthesized and the conjugation was confirmed by Fourier transform infrared spectroscopy. The multi-walled carbon nanotubes were characterized for their particle size, polydispersity, zeta potential, surface morphology, drug encapsulation efficiency and in vitro release study. The in vitro cellular uptake, cytotoxicity, and cell cycle analysis of the docetaxel/coumarin-6 loaded multi-walled carbon nanotubes were carried out to compare the effectiveness of the formulations. The biocompatibility and safety of chitosan-folate conjugated multi-walled carbon nanotubes was analyzed by lung histopathology in comparison with marketed docetaxel formulation (Docel™) and acylated multi-walled carbon nanotubes. The cellular internalization study shown that the chitosan-folate conjugated multi-walled carbon nanotubes could be easily internalized into the lung cancer cells through a folate receptor-mediated endocytic pathway. The IC50 values exhibited that chitosan-folate conjugated multi-walled carbon nanotubes could be 89-fold more effective than Docel™ in human lung cancer cells (A549 cells). © 2017 Elsevier B.V.
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 and evaluation of chitosan nanoparticles as novel drug carrier for the delivery of rivastigmine to treat Alzheimer's disease
(Newlands Press Ltd, 2011) Barnabas Wilson; Malay K. Samanta; Madaswamy S. Muthu; Ganesan Vinothapooshan
Aim: The objective of the study was to develop chitosan nanoparticles of the drug rivastigmine and to study the effect of polysorbate 80 coating on its biodistribution. Results: Chitosan nanoparticles containing rivastigmine were prepared by spontaneous emulsification. The mean size of the particles was 47 ± 4 nm. ζ potential analysis demonstrated a positive charge for the particles and coating with polysorbate 80 slightly reduced the surface charge of the particles. A biphasic release pattern was observed for the release of drug from the nanoparticles. Release of the drug from nanoparticles was diffusion controlled and the mechanism of drug release was Fickian. Conclusion: The biodistribution studies demonstrated that coating of nanoparticles with 1% polysorbate 80 altered the uptake of nanoparticles by different organs. © 2011 Future Science 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.
Development of docetaxel-loaded vitamin e TPGS micelles: Formulation optimization, effects on brain cancer cells and biodistribution in rats
(2012) Madaswamy S. Muthu; Sneha Avinash Kulkarni; Yutao Liu; Si-Shen Feng
Aim: This work aimed to develop docetaxel-loaded D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for brain cancer chemotherapy by taking advantage of polyethylene glycol for its long half-life in circulation and vitamin E for its high cellular uptake. Material and methods: TPGS micelles containing docetaxel or coumarin-6 were prepared by the solvent casting method and the direct dissolution method at high, moderate and low drug-loading levels. Results and discussion: The particle size of the docetaxel-loaded TPGS micelles ranged between 12 and 14 nm. Docetaxel formulated in the TPGS micelles of high, moderate and low drug-loading levels achieved lower IC 50 values compared with Taxotere® after 24-h incubation with C6 glioma brain cancer cells. The TPGS has much lower critical micelle concentration than most phospholipids in micellar formulation, which can be an efficient drug carrier across the blood brain-barrier with high drug encapsulation efficiency, cell uptake, cytotoxicity and desired biodistribution of the formulated drug. © 2012 Future Medicine Ltd.
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.
Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery
(Elsevier Ltd, 2016) Rahul Pratap Singh; Gunjan Sharma; Sonali; Sanjay Singh; Shashikant C.U. Patne; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). d-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC50 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P < 0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™. © 2016 Elsevier B.V. All rights reserved.
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.
Emerging patents for cancer-targeted nanomedicines
(2012) Madaswamy S. Muthu; Bajarangprasad L. Pandey; Ashish K. Sahu; Chellappa V. Rajesh
[No abstract available]
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