Displaying publications 1 - 20 of 74 in total

  1. Tekade RK, Tekade M, Kesharwani P
    Drug Discov Today, 2016 Jul 2.
    PMID: 27380716 DOI: 10.1016/j.drudis.2016.06.029
    The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy.
  2. Singh G, Kesharwani P, Srivastava AK
    Curr Drug Deliv, 2018;15(3):312-320.
    PMID: 29165080 DOI: 10.2174/1567201814666171120125916
    BACKGROUND: Tuberculosis is an infection and caused by gentle growing bacteria. The Internet provides opportunities for people with tuberculosis (TB) to connect with one another to address these challenges.

    OBJECTIVE: The aim of this paper is to introduce readers to the platforms on which Tuberculosis participants interact, to discuss reasons for and risks associated with TB-related activity, and to review research related to the potential impact of individual participation on TB outcomes.

    METHODS: Research and online content related to Tuberculosis online activity is reviewed, however, the difficulty in accurate prescribing and adhering to these protocols and the emergence of M. tuberculosis strains resistant to multiple drugs and drug-drug interactions that interfere with optimal treatment of Tuberculosis and co-infected patients with the different disease has generated a pressing need for improved Tuberculosis therapies.

    RESULTS: Together with the ominous global burden of Tuberculosis, those shortcomings of current medication have contributed to a renewed interest in the development of improved drugs and protocols for the medication of Tuberculosis. This article features obstacles related with the enhanced utilization of existing drugs and difficulties related with the advancement of enhanced products, concentrating on perspectives characteristic in Tuberculosis drug clinical improvement. The participation includes peer support, advocacy, self-expression, seeking and sharing TB information, improving approaches to Tuberculosis data management, and humour.

    CONCLUSION: This article highlights hurdles related to the optimised use of existing drugs and challenges related to the development of improved products, focusing on aspects inherent in Tuberculosis drug clinical development. Concluding comments offer processes for more efficient development of Tuberculosis therapies and increase the quality of life.

  3. Gorain B, Choudhury H, Pandey M, Kesharwani P
    Mater Sci Eng C Mater Biol Appl, 2018 Oct 01;91:868-880.
    PMID: 30033322 DOI: 10.1016/j.msec.2018.05.054
    Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with reduction in associated toxicities, whereas incorporation of TPGS could further facilitate delivery in MDR through alteration of its inherent physicochemical properties. Current article therefore puts into perspective on nanocarrier-based recent researches of PTX with special stress towards TPGS-nanoparticle-mediated delivery in the improvement of cancer treatment and then accompanied with the discussion on distinct influence of the fabrication process. Such dynamic fabrications of the nanoparticulate therapy stimulate cellular interaction with frontier area for future research in tumor targeting potential.
  4. Ghanghoria R, Kesharwani P, Jain NK
    Mini Rev Med Chem, 2017;17(18):1713-1724.
    PMID: 26891934 DOI: 10.2174/1389557516666160219122002
    The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer.
  5. Mishra V, Patil A, Thakur S, Kesharwani P
    Drug Discov Today, 2018 06;23(6):1219-1232.
    PMID: 29366761 DOI: 10.1016/j.drudis.2018.01.006
    Nanotechnology has gained significant interest from biomedical and analytical researchers in recent years. Carbon dots (C-dots), a new member of the carbon nanomaterial family, are spherical, nontoxic, biocompatible, and discrete particles less than 10nm in diameter. Research interest has focused on C-dots because of their ultra-compact nanosize, favorable biocompatibility, outstanding photoluminescence, superior electron transfer ability, and versatile surface engineering properties. C-dots show significant potential for use in cellular imaging, biosensing, targeted drug delivery, and other biomedical applications. Here we discuss C-dots, in terms of their physicochemical properties, fabrication techniques, toxicity issues, surface engineering and biomedical potential in drug delivery, targeting as well as bioimaging.
  6. Zeeshan F, Tabbassum M, Kesharwani P
    Protein J, 2019 10;38(5):551-564.
    PMID: 31054037 DOI: 10.1007/s10930-019-09837-4
    Protein drugs are important therapeutic agents however; they may degrade during formulation processing. The objective of this study was to investigate the correlation between secondary structure alterations and the retentions of biological activity of protein upon the application of thermal stress. Catalase, horseradish peroxidase and α- chymotrypsin were employed as model proteins. Each protein was heated in a solid and solution state at a temperature of 70 °C for 1 h. Attenuated total reflectance Fourier transform infrared spectroscopy, size-exclusion chromatography and biological activity assay were performed. Results showed that heat-exposure of protein solids at 70 °C caused minimum changes in secondary structure and biological activity was almost retained. However, thermal exposure of protein aqueous solution induced significant changes in the secondary structure indicated by area overlap values and caused considerable reduction in the biological activity. The changes in secondary structures were found to be in full alignment with the loss of biological activity for both protein solids as well as aqueous solutions. Catalase lost entire biological activity upon heating in the solution state. In conclusion, the findings of the present study indicate a direct correlation between protein secondary structure alterations and the retention of biological activity which can be taken into account during the development and delivery of protein drugs formulations.
  7. Mansuri S, Kesharwani P, Tekade RK, Jain NK
    Eur J Pharm Biopharm, 2016 May;102:202-13.
    PMID: 26563727 DOI: 10.1016/j.ejpb.2015.10.015
    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ.
  8. Madheswaran T, Baskaran R, Yoo BK, Kesharwani P
    J Pharm Sci, 2017 11;106(11):3385-3394.
    PMID: 28652158 DOI: 10.1016/j.xphs.2017.06.016
    In this study, we developed positively charged liquid crystalline nanoparticles (LCN) coated with chitosan (CHI) to enhance the skin permeation and distribution of 5α-reductase inhibitors for the treatment of androgenetic alopecia. LCN and surface-modified LCN (CHI-LCN) were prepared by ultrasonication method, and their physicochemical properties were characterized. In vitro and in vivo skin permeation and retention were studied using porcine abdominal skin and mice skin using the Franz diffusion cell. Skin distribution and cellular uptake of LCN and CHI-LCN were also investigated. The particle size and surface charge were 244.9 ± 2.1 nm and -19.2 ± 1.1 mV, respectively, for LCNs and 300.0 ± 7.6 nm and 24.7 ± 2.4 mV, respectively, for CHI-LCN. The permeation of 5α-reductase inhibitors was significantly greater with CHI-LCN compared with LCN, whereas there was no significant difference observed in the skin distribution. In fluorescence studies, fluorescence intensity was higher for CHI-LCNs throughout the skin, whereas more intense fluorescence was seen only in the epidermis layer for LCN. CHI-LCN showed greater cellular uptake than LCN, resulting in internalization of 98.5 ± 1.9% of nanoparticles into human keratinocyte cells. In conclusion, surface modification of LCN with CHI is a promising strategy for increasing skin permeation of 5α-reductase inhibitors for topical delivery.
  9. Soni N, Soni N, Pandey H, Maheshwari R, Kesharwani P, Tekade RK
    J Colloid Interface Sci, 2016 Nov 01;481:107-16.
    PMID: 27459173 DOI: 10.1016/j.jcis.2016.07.020
    Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety.
  10. Ghanghoria R, Kesharwani P, Tekade RK, Jain NK
    J Control Release, 2018 01 10;269:277-301.
    PMID: 27840168 DOI: 10.1016/j.jconrel.2016.11.002
    Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.
  11. Khurana RK, Jain A, Jain A, Sharma T, Singh B, Kesharwani P
    Drug Discov Today, 2018 Apr;23(4):763-770.
    PMID: 29317341 DOI: 10.1016/j.drudis.2018.01.021
    Several randomized clinical trials have divulged that administration of antioxidants during chemotherapy decreases the effectiveness of treatment. Hence, the characteristic feature of this article is extensive assessment of putative benefits and potential risks of natural and synthetic antioxidant supplementation, administered with chemotherapy, based upon the available preclinical and clinical data. After analyzing mixed results, it was concluded that current FDA guidelines should be followed before supplementing antioxidants during cytotoxic treatment. Nevertheless, contradictory experimental animal models opposing human clinical trials discourage the concurrent administration of antioxidants ostensibly owing to the possibility of tumor protection and reduced survival.
  12. Tripathi PK, Gorain B, Choudhury H, Srivastava A, Kesharwani P
    Heliyon, 2019 Mar;5(3):e01343.
    PMID: 30957038 DOI: 10.1016/j.heliyon.2019.e01343
    Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes. However, its application is troublesome and inconvenient because of its associated side effects, including staining, burning sensation, irritation, and necrotizing effect on the diseased cells as well as on the normal cells. The purpose of the current investigation was to explore the potential of poly(amido) amine (PAMAM) dendrimers in the topical delivery of dithranol through a novel microsponge based gel. Generation-4 (G4) dendrimers were incorporated into the microsponge based gel formulation by quasi-emulsion solvent diffusion method with varying concentration of polymers, and evaluated for the morphology of the formulation, encapsulation efficiency and skin irritation potential. Percentage yield of the formulation was found to be 66.28%, whereas encapsulation efficiency was ranged between 71.33% to 49.21%, and an average particle size was ranged between 28 ± 1.12 μm to 130 ± 1.01 μm. Surface morphology of developed microsponge was confirmed by scanning electron microscopy, revealed micro-porous nature. The optimized microsponge formulation was found to be stable and recorded non-irritant during cutaneous application of the experimental animals. Further, the pharmacokinetic outcomes of study were showed prolong penetration of the drug through the skin, equivalent to the marketed formulation of dithranol. Therefore, it could be conferred that the microsponge formulation of the PAMAM entrapped dithranol can produce prolonged efficacy without producing toxicities to the skin, and thus can effectively be projected in the treatment of diseases like psoriasis.
  13. Gorain B, Choudhury H, Molugulu N, Athawale RB, Kesharwani P
    Front Public Health, 2020;8:606129.
    PMID: 33363098 DOI: 10.3389/fpubh.2020.606129
    Sudden outbreak of a new pathogen in numbers of pneumonic patients in Wuhan province during December 2019 has threatened the world population within a short period of its occurrence. This respiratory tract-isolated pathogen was initially named as novel coronavirus 2019 (nCoV-2019), but later termed as SARS-CoV-2. The rapid spreading of this infectious disease received the label of pandemic by the World Health Organization within 4 months of its occurrence, which still seeks continuous attention of the researchers to prevent the spread and for cure of the infected patients. The propagation of the disease has been recorded in 215 countries, with more than 25.5 million cases and a death toll of more than 0.85 million. Several measures are taken to control the disease transmission, and researchers are actively engaged in finding suitable therapeutics to effectively control the disease to minimize the mortality and morbidity rates. Several existing potential candidates were explored in the prevention and treatment of worsening condition of COVID-19 patients; however, none of the formulation has been approved for the treatment but used under medical supervision. In this article, a focus has been made to highlight on current epidemiology on the COVID-19 infection, clinical features, diagnosis, and transmission, with special emphasis on treatment measures of the disease at different stages of clinical research and the global economic influence due to this pandemic situation. Progress in the development on vaccine against COVID-19 has also been explored as important measures to immunize people. Moreover, this article is expected to provide information to the researchers, who are constantly combating in the management against this outbreak.
  14. Zeeshan F, Madheswaran T, Panneerselvam J, Taliyan R, Kesharwani P
    J Pharm Sci, 2021 Sep;110(9):3111-3117.
    PMID: 33989679 DOI: 10.1016/j.xphs.2021.05.001
    Human serum albumin or simply called albumin is a flexible protein employed as a carrier in the fabrication of albumin-based nanocarriers (ANCs) for the administration of cancer therapeutics. Albumin can contribute enhanced tumour specificity, reduced drug induced cytotoxicity and retain concentration of the therapeutically active agent such as drug, peptide, protein, and gene for a prolonged time duration. Nevertheless, apart from cancer management, ANCs are also employed in the diagnosis, imaging, and multimodal cancer therapy. This article figures out salient characteristics, design as well as categories of ANCs in the context of their application in cancer management. In addition, this review article discusses the fabrication methods of ANCs, use of ANCs in gene, cancer, and multimodal therapy along with cancer diagnosis and imaging. Lastly, this review also briefly discusses about (ANCs) formulations, commercial products, and those under clinical testing.
  15. Choudhury H, Gorain B, Pandey M, Khurana RK, Kesharwani P
    Int J Pharm, 2019 Jun 30;565:509-522.
    PMID: 31102804 DOI: 10.1016/j.ijpharm.2019.05.042
    The biological barriers in the body have been fabricated by nature to protect the body from foreign molecules. The successful delivery of drugs is limited and being challenged by these biological barriers including the gastrointestinal tract, brain, skin, lungs, nose, mouth mucosa, and immune system. In this review article, we envisage to understand the functionalities of these barriers and revealing various drug-loaded biodegradable polymeric nanoparticles to overcome these barriers and deliver the entrapped drugs to cancer targeted site. Apart from it, tissue-specific multifunctional ligands, linkers and transporters when employed imparts an effective active delivery strategy by receptor-mediated transcytosis. Together, these strategies enable to deliver various drugs across the biological membranes for the treatment of solid tumors and malignant cancer.
  16. Gorain B, Choudhury H, Nair AB, Dubey SK, Kesharwani P
    Drug Discov Today, 2020 07;25(7):1174-1188.
    PMID: 32344042 DOI: 10.1016/j.drudis.2020.04.013
    Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
  17. Dwivedi N, Shah J, Mishra V, Mohd Amin MC, Iyer AK, Tekade RK, et al.
    J Biomater Sci Polym Ed, 2016 May;27(7):557-80.
    PMID: 26928261 DOI: 10.1080/09205063.2015.1133155
    Worldwide, the cancer appeared as one of the most leading cause of morbidity and mortality. Among the various cancer types, brain tumors are most life threatening with low survival rate. Every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed. The dendrimeric approaches have a huge potential for diagnosis and treatment of brain tumor with targeting abilities of molecular cargoes to the tumor sites and the efficiency of crossing the blood brain barrier and penetration to brain after systemic administration. The various generations of dendrimers have been designed as novel targeted drug delivery tools for new therapies including sustained drug release, gene therapy, and antiangiogenic activities. At present era, various types of dendrimers like PAMAM, PPI, and PLL dendrimers validated them as milestones for the treatment and diagnosis of brain tumor as well as other cancers. This review highlights the recent research, opportunities, advantages, and challenges involved in development of novel dendrimeric complex for the therapy of brain tumor.
  18. Choudhary S, Jain A, Amin MCIM, Mishra V, Agrawal GP, Kesharwani P
    Colloids Surf B Biointerfaces, 2016 May 01;141:268-277.
    PMID: 26859118 DOI: 10.1016/j.colsurfb.2016.01.048
    The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment.
  19. Luong D, Kesharwani P, Deshmukh R, Mohd Amin MCI, Gupta U, Greish K, et al.
    Acta Biomater, 2016 10 01;43:14-29.
    PMID: 27422195 DOI: 10.1016/j.actbio.2016.07.015
    Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers.

    STATEMENT OF SIGNIFICANCE: It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers.

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