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Author: search.filters.author.Chitkara, DeepakSubject: search.filters.subject.Drug Delivery

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Now showing 1 - 7 of 7
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    Molecular medicines for cancer: concepts and applications of nanotechnology
    (CRC Press, 2019) Chitkara, Deepak; Mittal, Anupama
    The field of molecular medicine covers the medical interventions targeting molecular structures and mechanisms that are involved in disease progression. In cancer, several molecular mechanisms have been shown to impact its progression, aggressiveness and chemoresistance. Increasing evidence demonstrates the role of nanotechnology and outcome of molecular therapy. Several books have discussed molecular biology and mechanisms involved in cancer, but this text gives an account of molecular therapeutics in cancer relating to advancements of nanotechnology. It provides a description of the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology. Key Features: Provides current information in the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology Presents important aspects of nanotechnology in the site-specific delivery of anticancer agents Includes up to date information on oligonucleotide and gene based therapies in cancer Describes small targeted molecules, antibodies and oligonucleotides which have shown to selectively target the molecular structures thereby influencing signal transduction Facilitates discussion between researchers involved in cancer therapy and nanoscientists
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    Influence of Nanocarrier Type on the Drug Delivery Aspects of Docetaxel: Empirical Evidences
    (Springer, 2022-08) Chitkara, Deepak
    Docetaxel (DTX) is one of the anti-neoplastic drugs widely employed in breast cancer management. Along with advantages, several challenges are associated with administering the BCS class IV drugs like DTX. Looking into the promises of various nanotechnology-based drug delivery systems, it was envisioned to explore the influence of carrier type on the drug delivery outcome for this anticancer agent.
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    Hitting Multiple Cellular Targets in Triple-Negative Breast Cancer Using Dual-Action Cisplatin(IV) Prodrugs for Safer Synergistic Chemotherapy
    (ACS, 2022-05) Chitkara, Deepak
    Triple-negative breast cancer (TNBC) cells show improved sensitivity for cisplatin therapy due to their defective DNA damage repair system. However, the clinical utilization of cisplatin is limited by dose-dependent systemic toxicities and chemoresistance. Cisplatin Pt(IV) derivatives having kinetically inert octahedral geometry provide an effective strategy to overcome these limitations. Upon cellular reduction, these derivatives release cisplatin and axial ligands, acting as dual-action prodrugs. Hereby, we have developed three cisplatin(IV) conjugates using distinct bioactive axial moieties (valproate, tocopherol, and chlorambucil), which can synergistically complement cisplatin activity and attack multiple cellular targets. The designed derivatives showcased enhanced antiproliferative activity and improved therapeutic synergism along with a noteworthy cisplatin dose reduction index in a panel of six cancer cells. These Pt(IV) derivatives remarkably improved cellular drug uptake and showed lower dependency on copper transporter 1 (Ctr1) for uptake than cisplatin. The results of enhanced in vitro activity were well corroborated by in vivo efficacy testing in the 4T1 cell-based TNBC model, showcasing ∼2–7-folds higher tumor volume reduction for Pt(IV) derivatives than cisplatin. In addition, the designed derivatives significantly reduced the nephrotoxicity risk involved in cisplatin therapy, indicated by systemic toxicity biomarkers and organ histopathology. The results indicated that cisplatin(IV) derivatives could open new avenues for safer synergistic chemotherapy in TNBC.
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    2, 2-Bis (hydroxymethyl) propionic acid based cyclic carbonate monomers and their (co) polymers as advanced materials for biomedical applications
    (Elsevier, 2021-08) Chitkara, Deepak; Mittal, Anupama
    Designing grafted biodegradable polymers with tailored multi-functional properties is one of the most researched fields with extensive biomedical applications. Among many biodegradable polymers, polycarbonates have gained much attention due to their ease of synthesis, high drug loading, and excellent biocompatibility profiles. Among various monomers, 2,2-bis(hydroxymethyl) propionic acid (bis-MPA) derived cyclic carbonate monomers have been extensively explored in terms of their synthesis as well as their polymerization. Since the late 90s, significant advancements have been made in the design of bis-MPA derived cyclic carbonate monomers as well as in their reaction schemes. Currently, bis-MPA derived polycarbonates have taken a form of an entire platform with a multitude of applications, the latest being in the field of nanotechnology, targeted drug, and nucleic acid delivery. The present review outlines an up to date developments that have taken place in the last two decades in the design, synthesis, and biomedical applications of bis-MPA derived cyclic carbonates and their (co)polymers
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    Micellar Delivery of Cyclopamine and Gefitinib for Treating Pancreatic Cancer
    (ACS, 2012-07) Chitkara, Deepak
    Hedgehog (Hh) and epidermal growth factor receptor (EGFR) signaling are involved in pancreatic cancer progression. Targeting these pathways simultaneously with cyclopamine (Hh inhibitor) and gefitinib (EGFR inhibitor) is a promising approach for treating pancreatic cancer. However, the major limitation for effective clinical translation of these molecules is their low aqueous solubility. We have previously demonstrated that methoxy polyethyleneglycol-b-poly(carbonate-co-lactic acid) {mPEG-b-P(CB-co-LA)} copolymer solubilizes hydrophobic anticancer drugs and has the potential to deliver to tumors by an enhanced permeability and retention (EPR) effect. In this study, using the nanoprecipitation method, cyclopamine and gefitinib were efficiently loaded into mPEG-b-P(CB-co-LA) micelles with encapsulation efficiencies of 94.4 and 88.6%, respectively. These micelles had a narrow particle size distribution with a mean particle size of 54.3 nm and a PDI of 0.14. Combination therapy showed a synergistic effect against L3.6pl cells but an additive effect against MIA PaCa-2cells. Caspase 3/7 activity was also increased when this combination therapy was used, indicating apoptotic cell death. Gene and protein expression analysis indicated cross-talk between Hh and EGFR signaling. Furthermore, the combination decreased tumor growth rate in L3.6pl-derived xenograft mouse tumors. These data suggest the applicability of our micellar system to effectively load and deliver cyclopamine and gefitinib for combination chemotherapy.
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    Polyanhydrides as localized drug delivery carrier: an update
    (Taylor & Francis, 2008-08) Chitkara, Deepak
    There is a continuing thrust to increase the efficacy and reduce the toxicity of existing and new drug molecules for their better usage to treat disease. Localized drug delivery has been explored in the same way, which can provide a platform to target local diseased tissues and can reduce the burden on the body by reducing the dose size and hence the dose-related toxicity of the molecules. Various polymers have evolved for the purpose of localized drug delivery, however, polyanhydrides are considered the best, supported by products in the clinical phases. Objective: To demonstrate the advantages of localized delivery using basic concepts and describing polyanhydride carrier with products such as Gliadel® and Septacin™. Methods: The rationale behind localized drug delivery and the carrier for the same are dealt with. Polyanhydrides discussed in detail are those from subclasses that have been given less emphasis previously and have been developed or investigated in the last 5 years. Results/conclusion: From the recent update on polyanhydrides, it can be concluded that these polymers have great potential as localized drug delivery carriers due to the versatility of their properties. However, the quest to stabilize the system in order to achieve a long shelf life remains ongoing.
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    Biodegradable Injectable In Situ Depot-Forming Drug Delivery Systems
    (Wiley, 2006-11) Chitkara, Deepak
    The scope of drug-delivery systems has expanded significantly in recent years providing new ways to deliver life saving therapeutics to patients. The development of new injectable drug-delivery systems has provided new vistas and opened up unexplored horizons in the field of science, particularly in controlled drug delivery since these systems possess unique advantages over traditional ones, which include ease of application, and localized and prolonged drug delivery. In the past few years, an increasing number of such systems has been reported in the literature for various biomedical applications, including drug delivery, cell encapsulation, and tissue repair. These are injectable fluids that can be introduced into the body in a minimally invasive manner prior to solidifying or gelling within the desired site. For this purpose both natural (chitosan, alginates) as well as synthetic polymers (PEGylated polyesters, ricinoleic acid-based polymers) have been utilized. These systems have been explored widely for the delivery of various therapeutic agents ranging for anti-neoplastic agents like paclitaxel to proteins and peptides such as insulin, almost covering every segment of the pharmaceutical field. This manuscript focuses on the recent advancements in the area of in situ forming biodegradable polymeric drug-delivery systems.