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      A Pillararene-Based Ternary Drug-Delivery System with Photocontrolled Anticancer Drug Release

      Author(s): 1 , 2 , 2 , 2 , 1
      Publication date (Electronic):
      Journal: Small
      Publisher: Wiley

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          Abstract

          A novel ternary drug delivery system (DDS) is constructed using a photodegradable anticancer prodrug (Py-Cbl), a water-soluble pillararene supramolecular container (WP6), and the diblock copolymer methoxy-poly(ethylene glycol)114 -block-poly(L -lysine hydrochloride)200. This DDS successfully addresses three important issues: enhancement of the water solubility of the anticancer prodrug; controlled release of the anticancer drug; accurate and quantitative measurement of the drug release.

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          Large porous particles for pulmonary drug delivery.

          D A Edwards, J. Hanes, G Caponetti … (1997)
          A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.
          Article 0 comments Cited 167 times – based on 0 reviews     Review now
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            Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture.

            Megan Fox, Francis C. Szoka, Jean Fréchet (2009)
            Chemotherapy can destroy tumors and arrest cancer progress. Unfortunately, severe side effects (treatment is usually a series of injections of highly toxic drugs) often restrict the frequency and size of dosages, much to the detriment of tumor inhibition. Most chemotherapeutic drugs have pharmacokinetic profiles with tremendous potential for improvement. Water-soluble polymers offer the potential to increase drug circulation time, improve drug solubility, prolong drug residence time in a tumor, and reduce toxicity. Cytotoxic drugs that are covalently attached to water-soluble polymers via reversible linkages more effectively target tumor tissue than the drugs alone. Macromolecules passively target solid tumor tissue through a combination of reduced renal clearance and exploitation of the enhanced permeation and retention (EPR) effect, which prevails for fast-growing tumors. Effective drug delivery involves a balance between (i) elimination of the polymeric drug conjugate from the bloodstream by the kidneys, liver, and other organs and (ii) movement of the drug out of the blood vasculature and into the tumor (that is, extravasation). Polymers are eliminated in the kidney by filtration through pores with a size comparable to the hydrodynamic diameter of the polymer; in contrast, the openings in the blood vessel structures that traverse tumors are an order of magnitude greater than the diameter of the polymer. Thus, features that may broadly be grouped as the "molecular architecture" of the polymer, such as its hydrodynamic volume (or molecular weight), molecular conformation, chain flexibility, branching, and location of the attached drug, can greatly impact elimination of the polymer from the body through the kidney but have a much smaller effect on the extravasation of the polymer into the tumor. Molecular architecture can in theory be adjusted to assert essentially independent control over elimination and extravasation. Understanding how molecular architecture affects passage of a polymer through a pore is therefore essential for designing polymer drug carriers that are effective in passively delivering a drug payload while conforming to the requirement that the polymers must eventually be eliminated from the body. In this Account, we discuss examples from in vivo studies that demonstrate how polymer architectural features impact the renal filtration of a polymer as well as tumor penetration and tumor accumulation. In brief, features that inhibit passage of a polymer through a pore, such as higher molecular weight, decreased flexibility, and an increased number of polymer chain ends, help prevent elimination of the polymer by the kidneys and can improve blood circulation times and tumor accumulation, thus improving therapeutic effectiveness.
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              Disulfide-cleavage-triggered chemosensors and their biological applications.

              Min-Hee Lee, Zhigang Yang, Choon Woo Lim … (2013)
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                Author and article information

                Journal
                Title: Small
                Abbreviated Title: Small
                Publisher: Wiley
                ISSN: 16136810
                Publication date Created: February 2015
                Publication date (Print): February 2015
                Publication date (Electronic): October 15 2014
                Volume: 11
                Issue: 8
                Pages: 919-925
                Affiliations
                [1 ]State Key Laboratory of Chemical Engineering; Department of Chemistry; Zhejiang University; Hangzhou 310027 P. R. China
                [2 ]MOE Key Laboratory of Macromolecular Synthesis and Functionalization; Department of Polymer Science and Engineering; Zhejiang University; Hangzhou 310027 P. R. China
                Article
                DOI: 10.1002/smll.201402236
                PubMed ID: 25318658
                SO-VID: e20b5aa7-3e30-4b1e-a8a9-c413feebe4dc
                Copyright © © 2014
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

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