Browsing by Author "Rahul Pratap Singh"

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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.
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.
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.
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.
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.
Nanotheranostics: Emerging strategies for early diagnosis and therapy of brain cancer
(Ivyspring International Publisher, 2018) Sonali; Matte Kasi Viswanadh; Rahul Pratap Singh; Poornima Agrawal; Abhishesh Kumar Mehata; Datta Maroti Pawde; Narendra; Roshan Sonkar; Madaswamy Sona Muthu
Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems established till now in the research field. These include gold nanoparticles, carbon nanotubes, magnetic nanoparticles, mesoporous silica nanoparticles, quantum dots, polymeric nanoparticles, upconversion nanoparticles, polymeric micelles, solid lipid nanoparticles and dendrimers for the advanced detection and treatment of brain cancer with advanced features. Also, we included the role of three-dimensional models of the BBB and cancer stem cell concept for the advanced characterization of nanotheranostic systems for the unification of diagnosis and treatment of brain cancer. In future, brain nanotheranostics will be able to provide personalized treatment which can make brain cancer even remediable or at least treatable at the primary stages. © Ivyspring International Publisher.
RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy
(Elsevier B.V., 2023) Bhavna Yadav; Mahima Chauhan; Saurabh Shekhar; Abhitinder Kumar; Abhishesh Kumar Mehata; Amit Kumar Nayak; Rohit Dutt; Vandana Garg; Vikas Kailashiya; Madaswamy S. Muthu; Sonali; Rahul Pratap Singh
Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100–200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer. © 2023 Elsevier B.V.
RGD-TPGS decorated theranostic liposomes for brain targeted delivery
(Elsevier B.V., 2016) Sonali; Rahul Pratap Singh; Gunjan Sharma; Lakshmi Kumari; Biplob Koch; Sanjay Singh; Shreekant Bharti; Paruvathanahalli Siddalingam Rajinikanth; Bajarangprasad L. Pandey; Madaswamy S. Muthu
The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes, which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and electrospray ionisation (ESI) mass spectroscopy (ESI–MS). The theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release study. Biocompatibility and safety of theranostic liposomes were studied by reactive oxygen species (ROS) generation study and histopathology of brain. In-vivo study was performed for determination of brain theranostic effects in comparison with marketed formulation (Docel™) and free QDs. The particle sizes of the non-targeted and targeted theranostic liposomes were found in between 100 and 200 nm. About 70% of drug encapsulation efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated liposomes was sustained for more than 72 h with 80% of drug release. The in-vivo results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and 6.98-fold more effective than Docel™ after 2 h and 4 h treatments, respectively. Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation effectively, and did not show any signs of brain damage or edema in brain histopathology. The results of this study have indicated that RGD-TPGS decorated theranostic liposomes are promising carrier for brain theranostics. © 2016 Elsevier B.V.
TPGS-chitosan cross-linked targeted nanoparticles for effective brain cancer therapy
(Elsevier Ltd, 2017) Poornima Agrawal; Rahul Pratap Singh; Sonali; Laksmi Kumari; Gunjan Sharma; Biplob Koch; Chellapa V. Rajesh; Abhishesh K. Mehata; Sanjay Singh; Bajarangprasad L. Pandey; Madaswamy S. Muthu
Brain cancer, up-regulated with transferrin receptor led to concept of transferrin receptor targeted anticancer therapeutics. Docetaxel loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-chitosan) nanoparticles were prepared with or without transferrin decoration. In vitro experiments using C6 glioma cells showed that docetaxel loaded chitosan nanoparticles, non-targeted and transferrin receptor targeted TPGS-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity. The IC50 values of non-targeted and transferrin receptor targeted nanoparticles from cytotoxic assay were found to be 27 and 148 folds, respectively higher than Docel™. In vivo pharmacokinetic study showed 3.23 and 4.10 folds enhancement in relative bioavailability of docetaxel for non-targeted and transferrin receptor targeted nanoparticles, respectively than Docel™. The results have demonstrated that transferrin receptor targeted nanoparticles could enhance the cellular internalization and cytotoxicity of docetaxel via transferrin receptor with improved pharmacokinetics for clinical applications. © 2017 Elsevier B.V.
Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics
(Taylor and Francis Ltd, 2016) Sonali; Rahul Pratap Singh; Nitesh Singh; Gunjan Sharma; Mahalingam R. Vijayakumar; Biplob Koch; Sanjay Singh; Usha Singh; Debabrata Dash; Bajarangprasad L. Pandey; Madaswamy S. Muthu
Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood–brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
Transferrin receptor targeted PLA-TPGS micelles improved efficacy and safety in docetaxel delivery
(Elsevier B.V., 2016) Rahul Pratap Singh; Gunjan Sharma; Sonali; Poornima Agrawal; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this work was to develop targeted polymeric micelles of poly-lactic acid-d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), which are assembled along with d-alpha-tocopheryl polyethylene glycol 1000 succinate-transferrin conjugate (TPGS-Tf), and loaded docetaxel (DTX) as a model drug for enhanced treatment of lung cancer in comparison to non-targeted polymeric micelles and DTX injection (Docel™). A549 human lung cancer cells were employed as an in vitro model to access cytotoxicity study of the DTX loaded polymeric micelles. The safety of DTX formulations were studied by the measurement of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the non-targeted and transferrin receptor targeted polymeric micelles could be 7 and 70 folds more effective than Docel™ after 24 h treatment with the A549 cells. Results suggested that transferrin receptor targeted polymeric micelles have showed better efficacy and safety than the non-targeted polymeric micelles and Docel™. © 2015 Elsevier B.V.
Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats
(Taylor and Francis Ltd, 2016) Sonali; Poornima Agrawal; Rahul Pratap Singh; Chellappa V. Rajesh; Sanjay Singh; Mahalingam R. Vijayakumar; Bajrangprasad L. Pandey; Madaswamy Sona Muthu
The effective treatment of brain cancer is hindered by the poor transport across the blood–brain barrier (BBB) and the low penetration across the blood–tumor barrier (BTB). The objective of this work was to formulate transferrin-conjugated docetaxel (DTX)-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for targeted brain cancer therapy. The micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, drug encapsulation efficiency, drug loading, in vitro release study and brain distribution study. Particle sizes of prepared micelles were determined at 25 °C by dynamic light scattering technique. The external surface morphology was determined by transmission electron microscopy analysis and atomic force microscopy. The encapsulation efficiency was determined by spectrophotometery. In vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the non-targeted and targeted micelles were <20 nm. About 85% of drug encapsulation efficiency was achieved with micelles. The drug release from transferrin-conjugated micelles was sustained for >24 h with 50% of drug release. The in vivo results indicated that transferrin-targeted TPGS micelles could be a promising carrier for brain targeting due to nano-sized drug delivery, solubility enhancement and permeability which provided an improved and prolonged brain targeting of DTX in comparison to the non-targeted micelles and marketed formulation. © 2015 Informa UK Limited, trading as Taylor & Francis Group.
Vitamin E TPGS conjugated carbon nanotubes improved efficacy of docetaxel with safety for lung cancer treatment
(Elsevier B.V., 2016) Rahul Pratap Singh; Gunjan Sharma; Sonali; Sanjay Singh; Mohan Kumar; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this work was to develop multi-walled carbon nanotubes (MWCNT), which were coated or covalently conjugated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and loaded docetaxel as a model drug for effective treatment to lung cancer in comparison with the commercial docetaxel injection (Docel™). The 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) study of the docetaxel/coumarin-6 loaded MWCNT. The safety of MWCNT formulations were studied by the measurements of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the TPGS conjugated MWCNT could be 80 folds more effective than Docel™ after 24 h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells were appeared significantly (P < 0.05) in the sub G1 phase for TPGS conjugated MWCNT. Results of TPGS conjugated MWCNT have showed better efficacy with safety than non-coated or TPGS coated MWCNT and Docel™. © 2016 Elsevier B.V.