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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Poly(d,l-lactide- co-glycolide)–chitosan composite particles for the treatment of lung cancer

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          Abstract

          Tumor heterogeneity makes combination chemotherapy one of the preferred modes of treatment regimens. In this work, sequential exposure of two anticancer agents, paclitaxel (Tx) followed by topotecan (TPT), was shown to have a synergistic effect on non-small cell lung cancer (NSCLC) cell line, NCI-H460. In order to improve patient compliance, the aforementioned concept was translated into a drug delivery system comprising of poly(d,l-lactide- co-glycolide) (PLGA)–chitosan composite particles. TPT-containing chitosan micro-/nanoparticles were prepared by the facile technique of electrospraying and encapsulated within PLGA microparticles using emulsion-solvent evaporation technique for delayed release of TPT. The formulation containing Tx- and TPT-loaded composite particles demonstrated synergism when exposed to NCI-H460 cellular aggregates (tumoroids) generated in vitro. Overall, the results of this study demonstrated the potential of the formulation containing Tx and PLGA–chitosan (TPT-loaded) composite particles for the treatment of lung cancer.

          Most cited references38

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          New methods of drug delivery.

          R. Langer (1990)
          Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.
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            Tumor pH and its measurement.

            Studies over the last few decades have demonstrated that the intracellular pH of solid tumors is maintained within a range of 7.0-7.2, whereas the extracellular pH is acidic. A low extracellular pH may be an important factor inducing more aggressive cancer phenotypes. Research into the causes and consequences of this acidic pH of tumors is highly dependent on accurate, precise, and reproducible measurements, and these have undergone great changes in the last decade. This review focuses on the most recent advances in the in vivo measurement of tumor pH by pH-sensitive PET radiotracers, MR spectroscopy, MRI, and optical imaging.
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              Drug synergism: its detection and applications.

              Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used concurrently. A quantitative assessment is necessary to distinguish these cases from simply additive action. This distinction is based on the classic pharmacologic definition of additivity that, briefly stated, means that each constituent contributes to the effect in accord with its own potency. Accordingly, the relative potency of the agents, not necessarily constant at all effect levels, allows a calculation using dose pairs to determine the equivalent of either agent and the effect by using the equivalent in the dose-response relation of the reference compound. The calculation is aided by a popular graph (isobologram) that provides a visual assessment of the interaction but also requires independent statistical analysis. The latter can be accomplished from calculations that use the total dose in a fixed-ratio combination along with the calculated additive total dose for the same effect. Different methods may be used, and each is applicable to experiments in which a single drug is given at two different sites. When departures from additivity are found, whether in "two-drug" or "two-site" experiments, the information is useful in designing new experiments for illuminating mechanisms. Several examples, mainly from analgesic drug studies, illustrate this application. Even when a single drug (or site) is used, its introduction places it in potential contact with a myriad of chemicals already in the system, a fact that underscores the importance of this topic in other areas of biological investigation.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2015
                16 April 2015
                : 10
                : 2997-3011
                Affiliations
                Department of Biological Sciences and Bioengineering, Indian Institute of Technology – Kanpur, Kanpur, Uttar Pradesh, India
                Author notes
                Correspondence: Dhirendra S Katti, Department of Biological Sciences and Bioengineering, Indian Institute of Technology – Kanpur, Kanpur 208016, Uttar Pradesh, India, Tel +91 512 259 4028, Fax +91 512 259 4010, Email dsk@ 123456iitk.ac.in
                Article
                ijn-10-2997
                10.2147/IJN.S78120
                4406260
                0db290d0-8ac4-47d4-9534-449beb8227ec
                © 2015 Arya and Katti. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                drug delivery system,solid tumor,paclitaxel,topotecan,sequential administration
                Molecular medicine
                drug delivery system, solid tumor, paclitaxel, topotecan, sequential administration

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