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  1. Yellepeddi VK, Sheshala R, McMillan H, Gujral C, Jones D, Raghu Raj Singh T
    Drug Discov. Today, 2015 Jul;20(7):884-9.
    PMID: 25668579 DOI: 10.1016/j.drudis.2015.01.013
    Punctal plugs (PPs) are miniature medical implants that were initially developed for the treatment of dry eyes. Since their introduction in 1975, many PPs made from different materials and designs have been developed. PPs, albeit generally successful, suffer from drawbacks such as epiphora and suppurative canaliculitis. To overcome these issues intelligent designs of PPs were proposed (e.g. SmartPLUG™ and Form Fit™). PPs are also gaining interest among pharmaceutical scientists for sustaining drug delivery to the eye. This review aims to provide an overview of PPs for dry eye treatment and drug delivery to treat a range of ocular diseases. It also discusses current challenges in using PPs for ocular diseases.
  2. Fatemian T, Othman I, Chowdhury EH
    Drug Discov. Today, 2014 Jan;19(1):71-8.
    PMID: 23974068 DOI: 10.1016/j.drudis.2013.08.007
    Resistance of cancer cells to anticancer drugs is the main reason for the failure of traditional cancer treatments. Various cellular components and different loops within the signaling pathways contribute to drug resistance which could be modulated with the aim to restore drug efficacy. Unveiling the molecular mechanisms for cancer drug resistance has now paved the way for the development of novel approaches to regulate the response rates to anticancer drugs at the genetic level. The recent progress on identification and validation of the vital genes directly or indirectly involved in development of cancer drug resistance with the aid of the specific knock down ability of RNA interference technology is discussed in this review.
  3. 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.
  4. Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U
    Drug Discov. Today, 2017 02;22(2):314-326.
    PMID: 27671487 DOI: 10.1016/j.drudis.2016.09.013
    Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
  5. Thanikachalam PV, Ramamurthy S, Wong ZW, Koo BJ, Wong JY, Abdullah MF, et al.
    Drug Discov. Today, 2018 Mar;23(3):460-480.
    PMID: 29107764 DOI: 10.1016/j.drudis.2017.10.020
    MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression at the post-translational level. miRNA-based therapeutic agents are important because of the functionality of miRNAs in regulating lipid and glucose metabolism and their role in the pathogenesis of metabolic disorders such as diabetes and obesity, where dysregulation leads to disease; they are also important in angiogenesis. miRNAs additionally serve as biomarkers in the diagnosis, prognosis and risk assessment of disease and in monitoring the response to treatment. Here, we provide a brief overview of progress in miRNA-based therapeutics in the preclinical and clinical setting and highlight the novel outcomes and opportunities in the diagnosis and treatment of metabolic conditions. In addition, we present the role of miRNAs in stem cell therapy which could have great potential in regenerative medicine.
  6. Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, et al.
    Drug Discov. Today, 2018 05;23(5):960-973.
    PMID: 29129804 DOI: 10.1016/j.drudis.2017.11.003
    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
  7. 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.
  8. 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.
  9. Han YL, Wang S, Zhang X, Li Y, Huang G, Qi H, et al.
    Drug Discov. Today, 2014 Jun;19(6):763-73.
    PMID: 24508818 DOI: 10.1016/j.drudis.2014.01.015
    Regenerative medicine has rapidly evolved over the past decade owing to its potential applications to improve human health. Targeted differentiations of stem cells promise to regenerate a variety of tissues and/or organs despite significant challenges. Recent studies have demonstrated the vital role of the physical microenvironment in regulating stem cell fate and improving differentiation efficiency. In this review, we summarize the main physical cues that are crucial for controlling stem cell differentiation. Recent advances in the technologies for the construction of physical microenvironment and their implications in controlling stem cell fate are also highlighted.
  10. Md S, Haque S, Madheswaran T, Zeeshan F, Meka VS, Radhakrishnan AK, et al.
    Drug Discov. Today, 2017 Aug;22(8):1274-1283.
    PMID: 28456749 DOI: 10.1016/j.drudis.2017.04.010
    Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.
  11. Wickens JM, Alsaab HO, Kesharwani P, Bhise K, Amin MCIM, Tekade RK, et al.
    Drug Discov. Today, 2017 04;22(4):665-680.
    PMID: 28017836 DOI: 10.1016/j.drudis.2016.12.009
    The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy.
  12. Meka VS, Sing MKG, Pichika MR, Nali SR, Kolapalli VRM, Kesharwani P
    Drug Discov. Today, 2017 11;22(11):1697-1706.
    PMID: 28683256 DOI: 10.1016/j.drudis.2017.06.008
    Global research on polyelectrolytes at a fundamental and applied level is intensifying because the advantages of sustainability are being accepted in academia and industrial research settings. During recent decades, polyelectrolytes became one of the most attractive subjects of scientific research owing to their great potential in the areas of advanced technologies. Polyelectrolytes are a type of polymer that have multitudinous ionizable functional groups. Ionized polyelectrolytes in solution can form a complex with oppositely charged polyelectrolytes - a polyelectrolyte complex (PEC). The present article provides a comprehensive review on PECs and their classification, theory and characterization, as well as a critical analysis of the current research.
  13. Kesharwani P, Gothwal A, Iyer AK, Jain K, Chourasia MK, Gupta U
    Drug Discov. Today, 2017 Jul 08.
    PMID: 28697371 DOI: 10.1016/j.drudis.2017.06.009
    Highly controllable dendritic structural design means dendrimers are a leading carrier in drug delivery applications. Dendrimer- and other nanocarrier-based hybrid systems are an emerging platform in the field of drug delivery. This review is a compilation of increasing reports of dendrimer interactions, such as dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid carriers. This should prompt entirely new research with promising results for these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from combining two already-established drug delivery platforms - could lead the way for the development of newer delivery systems with multiple applicability for latent theranostic applications in the future.
  14. Gorain B, Tekade M, Kesharwani P, Iyer AK, Kalia K, Tekade RK
    Drug Discov. Today, 2017 04;22(4):652-664.
    PMID: 28219742 DOI: 10.1016/j.drudis.2016.12.007
    To avoid tissue rejection during organ transplantation, research has focused on the use of tissue engineering to regenerate required tissues or organs for patients. The biomedical applications of hyperbranched, multivalent, structurally uniform, biocompatible dendrimers in tissue engineering include the mimicking of natural extracellular matrices (ECMs) in the 3D microenvironment. Dendrimers are unimolecular architects that can incorporate a variety of biological and/or chemical substances in a 3D architecture to actively support the scaffold microenvironment during cell growth. Here, we review the use of dendritic delivery systems in tissue engineering. We discuss the available literature, highlighting the 3D architecture and preparation of these nanoscaffolds, and also review challenges to, and advances in, the use dendrimers in tissue engineering. Advances in the manufacturing of dendritic nanoparticles and scaffold architectures have resulted in the successful incorporation of dendritic scaffolds in tissue engineering.
  15. Bapat RA, Joshi CP, Bapat P, Chaubal TV, Pandurangappa R, Jnanendrappa N, et al.
    Drug Discov. Today, 2019 01;24(1):85-98.
    PMID: 30176358 DOI: 10.1016/j.drudis.2018.08.012
    Maintenance of oral health is a major challenge in dentistry. Different materials have been used to treat various dental diseases, although treatment success is limited by features of the biomaterials used. To overcome these limitations, materials incorporated with nanoparticles (NPs) can be used in dental applications including endodontics, periodontics, tissue engineering, oral surgery, and imaging. The unique properties of NPs, including their surface:volume ratio, antibacterial action, physical, mechanical, and biological characteristics, and unique particle size have rendered them effective vehicles for dental applications. In this review, we provide insights into the various applications of NPs in dentistry, including their benefits, limitations, properties, actions and future potential.
  16. Mak KK, Pichika MR
    Drug Discov. Today, 2019 03;24(3):773-780.
    PMID: 30472429 DOI: 10.1016/j.drudis.2018.11.014
    Artificial intelligence (AI) uses personified knowledge and learns from the solutions it produces to address not only specific but also complex problems. Remarkable improvements in computational power coupled with advancements in AI technology could be utilised to revolutionise the drug development process. At present, the pharmaceutical industry is facing challenges in sustaining their drug development programmes because of increased R&D costs and reduced efficiency. In this review, we discuss the major causes of attrition rates in new drug approvals, the possible ways that AI can improve the efficiency of the drug development process and collaboration of pharmaceutical industry giants with AI-powered drug discovery firms.
  17. Madheswaran T, Kandasamy M, Bose RJ, Karuppagounder V
    Drug Discov. Today, 2019 Jul;24(7):1405-1412.
    PMID: 31102731 DOI: 10.1016/j.drudis.2019.05.004
    Lyotropic nonlamellar liquid crystalline nanoparticles (NPs) (LCN), such as cubosomes and hexosomes, are useful tools for applications in drug delivery because of their unique structural properties. LCNs are highly versatile carriers that can be applied for use with topical, oral, and intravenous treatments. In recent years, significant research has focused on improving their preparation and characterization, including controlling drug release and enhancing the efficacy of loaded bioactive molecules. Nevertheless, the clinical translation of LCN-based carriers has been slow. In this review, we highlight recent advances and challenges in the development and application of LCN, providing examples of their topical, oral, and intravenous drug delivery applications, and discussing translational obstacles to LCN as a NP technology.
  18. Cheong SL, Federico S, Spalluto G, Klotz KN, Pastorin G
    Drug Discov. Today, 2019 May 15.
    PMID: 31102728 DOI: 10.1016/j.drudis.2019.05.003
    Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
  19. Soo HL, Quah SY, Sulaiman I, Sagineedu SR, Lim JCW, Stanslas J
    Drug Discov. Today, 2019 May 30.
    PMID: 31154065 DOI: 10.1016/j.drudis.2019.05.017
    Andrographolide (AGP), a naturally occurring bioactive compound, has been investigated as a lead compound in cancer drug development. Its multidimensional therapeutic effects have raised interest among medicinal chemists, which has led to extensive structural modification of the compound, resulting in analogues with improved pharmacological and pharmaceutical properties. Nevertheless, the analogues with the improved properties need to be rigorously studied to identify drug-like lead compounds. We scrutinised articles published from 2012 to 2018, to objectively provide opinions on the mechanisms of action of AGP and its analogues, as well as their potential as viable anticancer drugs. Preclinical and clinical data, along with the extensive medicinal chemistry efforts, indicate the compounds are potential anticancer agents with specific value in treating recalcitrant cancers such as pancreatic and lung cancers.
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