528
Views
13
CrossRef citations to date
0
Altmetric
Review Article

Subcellular drug targeting, pharmacokinetics and bioavailability

Pages 95-115 | Received 05 Aug 2013, Accepted 22 Sep 2013, Published online: 05 Nov 2013

References

  • Palakurthi S, Yellepeddi VK, Kumar A. Nanocarriers for cytosolic drug and gene delivery in cancer therapy. In: Dr. Sylwia Olsztynska, ed. Biomedical engineering, trends, research and technologies. Intech; 2011. Available from: http://www.intechopen.com/books/biomedical-engineering-trends-research-and-technologies/nanocarriers-forcytosolic-drug-and-gene-delivery-in-cancer-therapy [last accessed 11 Oct 2012]
  • Rajendran L, Knölker HJ, Simons K. Subcellular targeting strategies for drug design and delivery. Nature Rev Drug Discov 2010;9:29–42
  • Langer R. Perspectives: drug delivery-drugs on target. Science 2001;293:58–9
  • Solomon M, D’Souza GGM. Approaches to achieving sub-cellular targeting of bioactives using pharmaceutical nanocarriers. In: Prokop A, ed. Intracellular delivery: fundamentals and applications. Dordrecht, Heidelberg, London, New York: Springer; 2011:57--72
  • Stepensky D. Quantitative aspects of intracellularly-targeted drug delivery. Pharm Res 2010;27:2776–80
  • Vasir JK, Labhasetwar V. Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 2007;59:718–28
  • Gershell LJ, Atkins JH. A brief history of novel drug discovery technologies. Nature Rev Drug Discov 2003;2:321–7
  • Rawat A, Vaidya B, Khatri K, et al. Targeted intracellular delivery of therapeutics: an overview. Pharmazie 2007;62:643–58
  • Torchilin VP. Next step in drug delivery: getting to individual organelles. Drug Deliv Transl Res 2012;2:415–17
  • Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng 2006;8:343–75
  • Lim CS. Organelle-specific targeting in drug delivery and design. Adv Drug Deliv Rev 2007;59:697--822
  • Widder KJ, Senyei AE, Ranney DF. Magnetically responsive microspheres and other carriers for the biophysical targeting of antitumor agents. Adv Pharmacol Chemother 1977;16:213–71
  • Prokop A, Davidson JM. Nanovehicular intracellular delivery systems. J Pharm Sci 2008;97:3518–90
  • Leucuta SE. Nanotechnology for delivery of drugs and biomedical applications. Curr Clin Pharmacol 2010;5:257–80
  • Sultana S, Khan MR, Kumar M, et al. Nanoparticles-mediated drug delivery approaches for cancer targeting: a review. J Drug Target 2013;21:107–25
  • Couvreur P. Nanoparticles in drug delivery: past, present and future. Adv Drug Deliv Rev 2013;65:21–3
  • Peppas NA. Historical perspective on advanced drug delivery: how engineering design and mathematical modeling helped the field mature. Adv Drug Deliv Rev 2013;65:5–9
  • Venditto VJ, Szoka Jr FC. Cancer nanomedicines: so many papers and so few drugs!. Adv Drug Deliv Rev 2013;65:80–8
  • Torchilin VP. Passive and active drug targeting: drug delivery to tumors as an example. Handb Exp Pharmacol 2010;197:3–53
  • Torchilin VP. Intracellular delivery of protein and peptide therapeutics. Drug Discov Today: Technol 2008;2--3:e95--103
  • Hymel D, Peterson BR. Synthetic cell surface receptors for delivery of therapeutics and probes. Adv Drug Deliv Rev 2012;64:797–810
  • Weissig V, D’Souza GGM. An introduction to subcellular nanomedicine: current trends and future developments. Chapter 1. In: Weissig V, D’Souza GGM, eds. Organelle-specific pharmaceutical nanotechnology. Hoboken (NJ): John Wiley & Sons, Inc; 2010:1--13
  • Li SD. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharmaceutics 2008;5:496–504
  • Shafer SL. Pharmacokinetics and pharmacodynamics for anesthesiologists. Available from: http://www.scribd.com/doc/20424968/Pharmacokinetics-and-Pharmacodynamics-for-Anesthesiologists [last accessed 22 Mar 2013]
  • Dollery CT. Intracellular drug concentrations. Clin Pharmacol Ther 2013;93:263–6
  • Food and Drug Agency. CFR-Code of Federal Regulations Title 21 Part 320 Bioavailability and bioequivalence requirements; 2011
  • European Agency for the Evaluation of Medicinal Products. CPMP/EWP/QWP/1401/98 Note for Guidance on the Investigation of bioavailability and bioequivalence, London; 2000
  • Weigand WA, Jhawar AK. Dose-effect curves and relative biophasic drug levels: elucidation of these concepts and the illustration of their use for the determination of bioavailability, rate of absorption, and time course of pharmacological response. J Pharmacokin Pharmacodyn 1976;4:67–80
  • Leucuta SE. Systemic and biophase bioavailability and pharmacokinetics of nanoparticulate drug delivery systems. Curr Drug Deliv 2013;10:208–40
  • Sneh-Edri H, Stepensky D. ‘IntraCell’ plugin for assessment of intracellular localization of nano-delivery systems and their targeting to the individual organelles. Biochem Biophys Res Commun 2011;405:228–33
  • Chen ML. Chapter 20: Regulatory considerations for controlled release parenteral drug products. Loposomes and microspheres. In: Diane J, ed. Injectable Dispersed Systems formulation, processing, and performance. Burgess: CRC Press; 2005:621–44. doi: 10.1201/9780849350610.ch20
  • Adarsh S, Shah Viral A, Umesh U. Organelle specific targeted drug delivery -- a review. Int J Res Pharm Biomed Sci 2011;2:895–912
  • Yates JR III, Gilchrist A, Howell KE, Bergeron JJM. Proteomics of organelles and large cellular structures. Nat Rev Mol Cell Biol 2005;6:702–14
  • Alberts B, Johnson A, Lewis J, et al. Molecular biology of the cell. 4th ed. New York: Garland; 2002
  • Hung MC, Link W. Protein localization in disease and therapy. J Cell Sci 2011;124:3381–92
  • Darnell JE, Lodish HF, Baltimore D. Molecular cell biology. New York (NY): Scientific American Books; 1986
  • Mitragotri S. Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers. Adv Drug Deliv Rev 2013;65:100–3
  • Lodish H, Berk A, Zipursky SL, et al. Molecular cell biology. 4th ed. New York: W. H. Freeman; Chapter 15, Transport across cell membranes. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21525/ [last accessed 11 Oct 2012]
  • Walker L. Endocytosis and exocytosis. Available from: http://www.fastbleep.com/biology-notes/31/172/985 [last accessed 22 Mar 2013]
  • Nagle JF, Tristram-Nagle S. Structure of lipid bilayers. Biochim Biophys Acta 2000;1469:159–95
  • Doherty GJ, McMahon HT. Mechanisms of endocytosis. Annu Rev Biochem 2009;78:857–902
  • Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Contr Rel 2010;145:182–95
  • McMahon HT, Boucrot E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 2011;12:517–33
  • Mukherjee S, Ghosh RN, Maxfield FR. Endocytosis. Physiol Rev 1997;77:759–803
  • Simons K, Vaz WL. Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 2004;33:269–95
  • Prokop A, ed. Intracellular delivery. Fundamentals and applications. Dordrecht, Heidelberg, London, New York: Springer; 2011
  • Brown MS, Anderson RGW, Goldstein JL. Recycling receptors: the round trip itinerary of malignant membrane proteins. Cell 1983;32:663–7
  • Dharmawardhane S, Schurmann A, Sells MA, et al. Regulation of macropinocytosis by p21-activated kinase-1. Mol Biol Cell 2000;11:3341–52
  • Mayor S, Pagano RE. Pathways of clathrin independent endocytosis. Nature Rev Mol Cell Biol 2007;8:603–12
  • Falcone S, Cocucci E, Podini P, et al. Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events. J Cell Sci 2006;119:4758–69
  • Gruenberg J, Maxfield FR. Membrane transport in the endocytic pathway. Curr Opin Cell Biol 1995;7:552–63
  • Bareford LM, Swaan PW. Endocytic mechanisms for targeted drug delivery. Adv Drug Deliv Rev 2007;59:748–58
  • Leucuta SE. Drug delivery systems with modified release for systemic and biophase bioavailability. Curr Clin Pharmacol 2012;7:282–317
  • Fang J, Sawa T, Maeda H. Factors and mechanism of “EPR” effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv Exp Med Biol 2003;519:29–49
  • Alving CR. Macrophages as targets for delivery of liposome encapsulated antimicrobial agents. Adv Drug Deliv Rev 1988;2:107–28
  • Poznansky M, Juliano RL. Biological approaches to the controlled delivery of drugs: a critical review. Pharmacol Rev 1984;36:277–336
  • Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Contr Rel 2001;74:47–61
  • Gref R, Domb A, Quellec P, et al. The controlled intravenous administration of drugs using PEG-coated sterically stabilized nanospheres. Adv Drug Deliv Rev 1995;16:215–33
  • Achim M, Risca R, Daicoviciu D, Leucuta SE. Gelatin microspheres containing epirubicin: pharmaceutical, pharmacokinetic and antitumour effect characterization. STP Pharma Sci 2002;12:275–82
  • Leucuta SE. The kinetics of in vitro release and pharmacokinetics of miotic response in rabbits of gelatin and albumin microspheres with pilocarpine. Int J Pharm 1988;41:213–17
  • Balacescu O, Neagoe I, Ola R, et al. Doxorubicin pharmacokinetics in organs after administration in mice as free or incapsulated in liposomes (in Romanian). Clujul Medical 2005a;78:192–8
  • Balacescu O, Neagoe I, Lazar V, et al. Pharmacogenomic study by microarray technology on the resistence at Cisplatin in ovarian cancer with in vitro and in vivo models (in Romanian). Farmacia 2005b;53:118–26
  • Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 2013;65:71–9
  • Akita H, Hatakeyama H, Khalil IA, et al. Delivery of nucleic acids and gene delivery. In: Ducheyne P, Healey KE, Hutmacher DW, et al., eds. Comprehensive biomaterials. Vol. 4. Elsevier; 2011:411--44
  • Vasir JK, Reddy MK, Labhasetwar VD. Nanosystems in drug targeting: opportunities and challenges. Curr Nanoscience 2005;1:47–64
  • Rosso F, Barbarisi M, Barbarisi A. Technology for biotechnology. Milan, Italy: Springer Verlag; 2011
  • Zhou Y, Kopecek J. Biological rationale for the design of polymeric anti-cancer nanomedicines. J Drug Target 2013;21:1–26
  • Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF. Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev 2013;1:131–8
  • Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003;422:37–44
  • Schmid SL. Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu Rev Biochem 1997;66:511–48
  • Hansen CG, Nichols BJ. Molecular mechanisms of clathrin-independent endocytosis. J Cell Sci 2009;122:1713–21
  • Juliano RL, Carver K, Cao C, Ming X. Receptors, endocytosis, and trafficking: the biological basis of targeted delivery of antisense and siRNA oligonucleotides. J Drug Target 2013;21:27–43
  • Le Roy C, Wrana JL. Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling. Nature Rev – Mol Cell Biol 2005;6:112–26
  • McPherson PS, Ritter B, Wendland B. Clathrin-mediated endocytosis. In: Madame Curie Bioscience Database. Austin (TX): Landes Bioscience; 2000--2013. Available from: http://www.ncbi.nlm.nih.gov/books/NBK6479/ [last accessed 12 Oct 2013]
  • Chen S. Tumor targeting drug delivery system of anticancer agent. Thesis, Stony Brook University; 2008
  • Bildstein L, Dubernet C, Couvreur P. Prodrug-based intracellular delivery of anticancer agents. Adv Drug Deliv Rev 2011;63:3–23
  • Damm EM, Pelkmans L, Kartenbeck J, et al. Clathrin- and caveolin-1-independent endocytosis. J Cell Biol 2005;168:477–88
  • Khanna VK. Targeted delivery of nanomedicines. ISRN Pharmacol 2012;2012:571394. doi: 10.5402/2012/571394. [last accessed 12 Oct 2013]
  • King GL, Feener EP. The biochemical and physiological characteristics of receptors. Adv Drug Deliv Rev 1998;29:197–213
  • Pattnaik G, Raju KSR, Heeralal B, Ali MS. Nanovehicles: an efficient carrier for active molecules for entry into the cell. Int J Pharm Sci Rev Res 2010;4:15–22
  • Feng Y, He X, Yang Y, et al. Current research on opioid receptor function. Curr Drug Targets 2012;13:230–46
  • Vyas SP, Sihorkar V. Endogenous carriers and ligands in non-immunogenic site-specific drug delivery. Adv Drug Deliv Rev 2000;43:101–64
  • Ansell SM, Harasym TO, Tardi PG, et al. Antibody conjugation methods for active targeting of liposomes. Methods Mol Med 2000a;25:51–68
  • Vyas SP, Singh A, Sihorkar V. Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting. Crit Rev Ther Drug Carrier Syst 2001;18:1–76
  • Bongrand P. Ligand receptor interactions. Rep Progr Phys 1999;62:921–68
  • Wileman T, Harding C, Stahl P. Receptor-mediated endocytosis. Biochem J 1985;232:1–14
  • Trapani G, Denora N, Trapani A, Laquintana V. Recent advances in ligand targeted therapy. J Drug Target 2012;20:1–22
  • Newsome BW, Ernstoff MS. The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived? Brit J Clin Pharmacol 2008;66:6–19
  • Strachan T, Read AP. Human molecular genetics. 2nd ed. New York: Wiley-Liss; 1999
  • Harris M. Monoclonal antibodies as therapeutic agents for cancer. Lancet Oncol 2004;5:292–302
  • Blanco MD, Teijon C, Olmo RM, Teijon JM. Targeted nanoparticles for cancer therapy. Chapter 9. In: Sezer AD, ed. Recent advances in novel drug carrier systems. InTech; 2012:241–78
  • Perry JJ, Staley JT, Lory S. Microbial Life, 1st ed. Sunderland: Sinauer Associates and Sumanas, Inc; 2002
  • Bruce A, Johnson A, Lewis J, et al. Molecular biology of the cell. 4th ed. New York: Garland Science; 2002
  • Yamashiro DJ, Maxfield FR. Acidification of endocytic compartments and the intracellular pathways of ligands and receptors. J Cell Biochem 1984;26:231–46
  • Bamrungsap S, Zhao Z, Chen T, et al. Nanotechnology in therapeutics, a focus on nanoparticles as a drug delivery system. Nanomedicine 2012;7:1253–71
  • Hildinger M, Dittmar MT, Schult-Dietrich P, et al. Membrane-anchored peptide inhibits human immunodeficiency virus entry. J Virol 2001;75:3038–42
  • Schulz R, Wehmeyer A, Schulz K. Opioid receptor types selectively cointernalize with G protein-coupled receptor kinases 2 and 3. J Pharmacol Exp Ther 2002;300:376–84
  • Gupta Y, Jain A, Jain P, Jain SK. Design and development of folate appended liposomes for enhanced delivery of 5-FU to tumor cells. J Drug Target 2007;15:231–40
  • Zhu Y, Li X, Schuchman EH, et al. Dexamethasone-mediated up-regulation of the mannose receptor improves the delivery of recombinant glucocerebrosidase to Gaucher macrophages. J Pharmacol Exp Ther 2004;308:705–11
  • Johannes L, Decaudin D. Protein toxins: intracellular trafficking for targeted therapy. Gene Ther 2005;12:1360–8
  • Duncan R. Designing polymer conjugates as lysosomotropic nanomedicines. Biochem Soc Trans 2007;35:56–60
  • Sobolev AS. Novel modular transporters delivering anticancer drugs and foreign DNA to the nuclei of target cancer cells. J BUON 2009;14:S33–42
  • Gupta B, Levchenko TS, Torchilin VP. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev 2005;57:637–51
  • Murthy N, Robichaud JR, Tirrell DA, et al. The design and synthesis of polymers for eukaryotic membrane disruption. J Contr Rel 1999;61:137–43
  • Sun Q, Cai S, Peterson BR. Selective disruption of early/recycling endosomes: release of disulfide-linked cargo mediated by a n-alkyl-3β-cholesterylamine-capped peptide. Am Chem Soc 2008;130:10064–5
  • Minchin RF, Yang S. Endosomal disruptors in non-viral gene delivery. Expert Opin Drug Deliv 2010;7:331–9
  • Maynard AD, Aitken RJ, Butz T. Safe handling of nanotechnology. Nature 2006;444:267–9
  • Nel AE. Understanding biophysiochemical interactions at the nano-bio interface. Nat Mater 2009;8:543–57
  • Zhang K, Fang H, Chen Z, et al. Nanostructures of various sizes, shapes and chemical compositions have gained access to the cell's interior with or without the assistance of CPPs. Bioconjug Chem 2008;19:1880–7
  • Paulo CSO, Pires das Neves R, Ferreira LS. Nanoparticles for intracellular-targeted drug delivery. Nanotechnology 2011;22:494002
  • Austin CD, De Maziere AM, Pisacane PI, et al. Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell 2004;15:5268–82
  • Liu D, Liu F, Liu Z, Wang L, Zhang N. Tumor specific delivery and therapy by double-targeted nanostructured lipid carriers with anti-VEGFR-2 antibody. Mol Pharm 2011;8:2291–301
  • Hild W, Pollinger K, Caporale A, et al. G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake. Proc Natl Acad Sci USA 2010;107:10667–72
  • Gabizon A, Tzemach D, Gorin J, et al. Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor expressing tumor models. Cancer Chemother Pharmacol 2010;66:43–52
  • Paulos CM, Reddy JA, Leamon CP, et al. Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery. Mol Pharmacol 2004;66:1406–14
  • Mauritz R, Peters GJ, Kathmann GAM, et al. Kinetics of reduced folate carrier- and membrane-associated folate receptor-mediated transport of antifolates. In: Milstien S, Kapatos G, Levine RA, Shane B, eds. Chemistry and biology of pteridines and folates. Dordrecht, Netherlands: Kluwer Academic Publications; 2002:649–53
  • Spinella MJ, Brigle KE, Sierra EE, Goldman ID. Distinguishing between folate receptor-mediated transport and reduced folate carrier-mediated transport in L1210 leukemia cells. J Biol Chemistry 1995;270:7842–9
  • Eliceiri BP, Cheresh DA. The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 1999;103:1227–30
  • Wagner S, Rothweiler F, Anhorn MG, et al. Enhanced drug targeting by attachment of an anti alphav integrin antibody to doxorubicin loaded human serum albumin nanoparticles. Biomaterials 2010;31:2388–98
  • Choi CH, Alabi CA, Webster P, Davis ME. Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles. Proc Natl Acad Sci USA 2010;107:1235–40
  • Jin H, Lovell JF, Chen J, et al. Mechanistic insights into LDL nanoparticle-mediated siRNA delivery. Bioconjug Chem 2012;23:33–41
  • Silva GA. Introduction to nanotechnology and its applications to medicine. Surg Neurol 2004;61:216–20
  • Faraji AH, Wipf P. Nanoparticles in cellular drug delivery. Bioorganic Med Chem 2009;17:2950–62
  • Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nature Rev Drug Discov 2005;4:145–60
  • Kayser O, Lemke A, Hernandez-Trejo N. The impact of nanobiotechnology on the development of new drug delivery systems. Curr Pharm Biotechnol 2005;6:3–5
  • Vauthier C, Bouchemal K. Methods for the preparation and manufacture of polymeric nanoparticles. Pharm Res 2009;26:1025–58
  • Yaduvanshi MR, Hemant YKS, Mangla NS, Hosakote GS. Nanoparticles, promising carriers in drug targeting: a review. Curr Drug Ther 2011;6:87–96
  • Breunig M, Bauer S, Goepferich A. Polymers and nanoparticles: intelligent tools for intracellular targeting? Eur J Pharm Biopharm 2008;68:112–28
  • Urban P, Valle-Delgado JJ, Moles E, et al. Nanotools for the delivery of antimicrobial peptides. Curr Drug Targets 2012;14:1158–72
  • Bhowmik D, Chiranjib B, Chandira RM, Jayakar B. Role of nanotechnology in novel drug delivery system. J Pharmaceut Sci Technol 2009;1:20–35
  • Zhang Y, Chan HF, Leong KW. Advanced materials and processing for drug delivery: the past and the future. Adv Drug Deliv Rev 2013;65:104–20
  • Silva JPS. Pharmaceutical formulation. Pharmaceut Anal Acta 2013;4:e145. doi: 10.4172/2153-2435.1000e145
  • Porfire AS, Zabaleta V, Gamazo C, et al. Influence of dextran on the bioadhesive properties of poly(anhydride) nanoparticles. Int J Pharm 2010;390:37–44
  • Arangoa MA, Campanero MA, Renedo MJ, et al. Gliadin nanoparticles as carriers for the oral administration of lipophilic drugs. Relationships between bioadhesion and pharmacokinetics. Pharm Res 2001;18:1521–7
  • Llabot JM, Salman H, Millotti G, et al. Bioadhesive properties ofpoly(anhydride) nanoparticles coated with different molecular weights chitosan. J Microencapsul 2011;28:455–63
  • Skiba M, Bounoure F, Barbot C, et al. Development of cyclodextrin microspheres for pulmonary drug delivery. J Pharm Pharmaceut Sci 2005;8:409–18
  • Sonvico F, Mornet S, Vasseur S, et al. Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments. Bioconjugate Chem 2005;16:1181–8
  • Mazzaferro S, Bouchemal K, Ponchel G. Oral delivery of anticancer drugs III: formulation using drug delivery systems. Drug Discov Today 2013;18:99–104
  • Panyam J, Zhou WZ, Prabha S, et al. Rapid endo-lysosomal escape of poly(dl-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J 2002;16:1217–26
  • Park K, Lee MY, Kim KS, Hahn SK. Target specific tumor treatment by VEGF siRNA complexed with reducible polyethyleneimine–hyaluronic acid conjugate. Biomaterials 2010;31:5258–65
  • Kopecek J. Polymer–drug conjugates: origins, progress to date and future directions. Adv Drug Deliv Rev 2013;65:49–59
  • Duncan R, Vicent MJ. Polymer therapeutics-prospects for 21st century: the end of the beginning. Adv Drug Deliv Rev 2013;65:60–70
  • Misra R, Sahoo SK. Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy. Eur J Pharm Sci 2010;39:152–63
  • Cartiera MS, Johnson KM, Rajendran V, et al. The uptake and intracellular fate of PLGA nanoparticles in epithelial cells. Biomaterials 2009;30:2790–8
  • Fox ME, Szoka FC, Fréchet JMJ. Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. Acc Chem Res 2009;42:1141–51
  • Hoffman AS. Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation. Adv Drug Deliv Rev 2013;65:10–16
  • Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 2013;65:36–48
  • Maurer N, Fenske DB, Cullis PR. Developments in liposomal drug delivery systems. Expert Opin Biol Ther 2001;1:923–47
  • Weissig V. From serendipity to mitochondria-targeted nanocarriers. Pharm Res 2011;28:2657–68
  • Gabizon AA. Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest 2001;19:424–36
  • Park JW, Benz CC, Martin FJ. Future directions of liposome- and immunoliposome-based cancer therapeutics. Semin Oncol 2004;31:196–205
  • Park JW, Kirpotin DB, Hong R, et al. Tumor targeting using anti-HER2 immunoliposomes. J Control Release 2001;74:95–113
  • Lu Y, Low PS. Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv Drug Deliv Rev 2002;54:675–93
  • Ishida OK, Maruyam K, Tanahashi H, et al. Liposomes bearing polyethyleneglycol coupled transferrin with intracellular targeting property to the solid tumors in vivo. Pharm Res 2001;18:1042–8
  • Fattal E, Couvreur P, Dubernet C. ‘Smart’ delivery of antisense oligonucleotides by anionic pH-sensitive liposomes. Adv Drug Deliv Rev 2004;56:931–46
  • Gaspar MM, Perez-Soler R, Cruz ME. Biological characterization of L asparaginase liposomal formulations. Cancer Chemother Pharmacol 1996;38:373–7
  • Felgner PL, Ringold GM. Cationic liposome-mediated transfection. Nature 1989;337:387–8
  • Audouy SA, de Leij LF, Hoekstra D, Molema G. In vivo characteristics of cationic liposomes as delivery vectors for gene therapy. Pharm Res 2002;19:1599–605
  • Sioud M, Sorensen DR. Cationic liposome-mediated delivery of siRNAs in adult mice. Biochem Biophys Res Commun 2003;312:1220–5
  • Kapoor M, Burgess DJ. Cellular uptake mechanisms of novel anionic siRNA lipoplexes. Pharm Res 2013;30:1161–75
  • Fraley R, Straubinger RM, Rule G, et al. Liposome mediated delivery of deoxyribonucleic acid to cells: enhanced efficiency of delivery by changes in lipid composition and incubation conditions. Biochemistry 1981;20:6978–87
  • Straubinger RM, Papahadjopoulos D. Liposomes as carriers for intracellular delivery of nucleic acids. Methods Enzymol 1983;101:512–27
  • Paecharoenchai O, Niyomtham N, Apirakaramwong A, et al. Structure relationship of cationic lipids on gene transfection mediated by cationic liposomes. AAPS Pharm Sci Tech 2012;13:1302–8
  • Tseng YL, Liu JJ, Hong RL. Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and TAT: a kinetic and efficacy study. Mol Pharmacol 2002;62:864–72
  • Kisel MA, Kulik LN, Tsybovsky IS, et al. Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in rat. Int J Pharm 2001;216:105–14
  • Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 2006;307:93–102
  • Mo Y, Lim LY. Paclitaxel-loaded PLGA nanoparticles: potentiation of anticancer activity by surface conjugation with wheat germ agglutinin. J Contr Rel 2005;108:244–62
  • Wang F, Wang YC, Dou S, et al. Doxorubicin-tethered responsive gold nanoparticles facilitate intracellular drug delivery for overcoming multidrug resistance in cancer cells. ACS Nano 2011;5:3679–92
  • Das S, Haddadi A, Veniamin S, Samuel J. Delivery of rapamycin-loaded nanoparticle down regulates ICAM-1 expression and maintains an immunosuppressive profile in human CD34+ progenitor-derived dendritic cells. J Biomed Mater Res 2008;85:983–92
  • Meng H, Liong M, Xia T, et al. Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano 2010;4:4539–50
  • Xu P. Targeted charge-reversal nanoparticles for nuclear drug delivery. Angew Chem Int Edn 2007;46:4999–5002
  • Cun D, Foged C, Yang M, et al. Preparation and characterization of poly(dl-lactide-co-glycolide) nanoparticles for siRNA delivery. Int J Pharm 2010;390:70–5
  • Ghosn B, Singh A, Li M, et al. Efficient gene silencing in lungs and liver using imidazole-modified chitosan as a nanocarrier for small interfering RNA. Oligonucleotides 2010;20:163–72
  • Han HD, Mangala LS, Lee JW, et al. Targeted gene silencing using RGD-labeled chitosan nanoparticles. Clin Cancer Res 2010;16:3910–22
  • Heidel JD, Davis ME. Clinical developments in nanotechnology for cancer therapy. Pharm Res 2011;28:187–99
  • Guo P, Coban O, Snead NM, et al. Engineering RNA for targeted siRNA delivery and medical application. Adv Drug Deliv Rev 2010;62:650–66
  • Mastrobattista E, Bravo SAS, van der Aa M, Crommelin DJA. Nonviral gene delivery systems: from simple transfection agents to artificial viruses. Drug Discovery Today: Technol 2005;2:103–9
  • Liu F, Huang L. Development of non-viral vectors for systemic gene delivery. J Contr Rel 2002;78:259–66
  • Al-Dosari MS, Gao X. Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 2009;11:671–81
  • Gao X, Kim KS, Liu D. Nonviral gene delivery: what we know and what is next. The AAPS J 2007;9:E92–104. Article 9. Available from: http://www.aapsj.org [last accessed 11 Oct 2012]
  • Lechardeur D, Verkman AS, Lukacs GL. Intracellular routing of plasmid DNA during non-viral gene transfer. Adv Drug Deliv Rev 2005;57:755–67
  • Kamiya H, Tsuchiya H, Yamazaki J, Harashima H. Intracellular trafficking and transgene expression of viral and non-viral gene vectors. Adv Drug Deliv Rev 2001;52:153–64
  • Akagi T, Shima F, Akashi M. Intracellular degradation and distribution of protein-encapsulated amphiphilic poly(amino acid) nanoparticles. Biomaterials 2011;32:4959–67
  • Hu Y, Litwin T, Nagaraja AR, et al. Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core–shell nanoparticles. Nano Lett 2007;7:3056–64
  • Bale SS, Kwon SJ, Shah DA, et al. Nanoparticle-mediated cytoplasmic delivery of proteins to target cellular machinery. ACS Nano 2010;4:1493–500
  • Lai PS, Pai CL, Peng CL, et al. Enhanced cytotoxicity of saporin by polyamidoamine dendrimer conjugation and photochemical internalization. J Biomed Mater Res A 2008;87:147–55
  • Marcato PD, Duran N. New aspects of nanopharmaceutical delivery systems. J Nanosci Nanotechnol 2008;8:1–14
  • Kamaly N, Xiao Z, Valencia PM, et al. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 2012;41:2971–3010
  • Ariens EJ. Drug design and cancer. 27th Annual Symposium on Fundamental Cancer Research, 1974, pp. 127–52. The Williams and Wilkins Company, Baltimore, and M.D. Anderson Hospital and Tumor Institute, Houston
  • Wermouth CG. The practice of medicinal chemistry. 2nd ed. London: Academic Press; 2003
  • Kwon Y. Handbook of essential pharmacokinetics, pharmacodynamics and drug metabolism for industrial scientists. New-York: Kluwer Academic Publications; 2002
  • Smith DA, van de Waterbeemd H, Walker DK. Pharmacokinetics and metabolism in drug design. 2nd ed. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim; 2006
  • Rosenbaum SE. Basic pharmacokinetics and pharmacodynamics. Hoboken: Wiley; 2011
  • Leucuta SE. Introduction to biopharmaceutics (in Romanian). Cluj-Napoca: Editura Dacia; 1975
  • Leucuta SE, Vlase L. Pharmacokinetics and metabolic drug interactions. Curr Clin Pharmacol 2006;1:5–20
  • Tihanyi K, Vastag M. Solubility, delivery and ADME problems of drugs and drug-candidates. Bentham Science Publishers Ltd (e-Book); 2011
  • Mager DE, Wyska E, Jusko WJ. Diversity of mechanism-based pharmacodynamic models. Drug Metab Dispos 2003;3:510–18
  • Notari RE. Biopharmaceutics and pharmacokinetics: an introduction. New York: M.Dekker; 1971
  • Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: M.Dekker; 1982
  • Leucuta SE, Pop RD. Pharmacokinetics (in Romanian). Editura Dacia: Cluj-Napoca; 1981
  • Benet LZ. Pharmacokinetics: basic principles and its use as a tool in drug metabolism. In: Mitchell JR, Horning MG, eds. Drug metabolism and drug toxicity. New York: Raven Press; 1984:199--221
  • Holford NH, Sheiner LB. Kinetics of pharmacologic response. Pharmacol Ther 1982;16:143–66
  • Hill A. The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol Lond 1920;40(Suppl.):IV--VII
  • Goutelle S, Maurin M, Rougier F, et al. The Hill equation: a review of its capabilities in pharmacological modelling. Fundam Clin Pharmacol 2008;22:633–48
  • Furchgott RF. The pharmacology of vascular smooth muscle. Pharmacol Rev 1955;7:183–265
  • Veng-Pedersen P, Modi NB. Pharmacodynamic system analysis of the biophase level predictor and the transduction function. J Pharm Sci 1992;81:925–34
  • Sheiner LB, Stanski DR, Vozeh S, et al. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 1979;25:358–71
  • Breimer DD, Danhof M. Relevance of the application of pharmacokinetic pharmacodynamic modelling concepts in drug development. The wooden shoe’ paradigm. Clin Pharmacokinet 1997;32:259–67
  • Danhof M, Jongh JD, De Lange EC, et al. Mechanism based pharmacokineticpharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis. Annu Rev Pharmacol Toxicol 2007;47:357–400
  • Letrent SP, Pollack GM, Brouwer KR, Brouwer KL. Effects of a potent and specific P-glycoprotein inhibitor on the blood-brain barrier distribution and antinociceptive effect of morphine in the rat. Drug Metab Dispos 1999;27:827–34
  • Danhof M, de Lange ECM, Della Pasqua OE, et al. Mechanism-based pharmacokinetic--pharmacodynamic (PK-PD) modeling in translational drug research. Trends Pharmacol Sci 2008;29:186–91
  • Yassen A, Kan J, Olofsen E, et al. Mechanism based pharmacokinetic--pharmacodynamic modeling of the respiratory depressant effect of buprenorphine and fentanyl in rats. J Pharmacol Exp Ther 2006;319:682–92
  • Thurber GM, Weissleder R. A systems approach for tumor pharmacokinetics. PLoS One 2011;6:e24696
  • Veng-Pedersen P, Mandema JW, Danhof M. Biophase equilibration times. J Pharm Sci 1991;80:881–6
  • Glass PSA, Shafer SL, Reves JG. Chapter 11, Intravenous drug delivery systems. In: Miller RD, Eriksson LI, Fleisher LA, et al., eds. Miller's anesthesia, 6th ed: expert Consult Premium Edition – Enhanced Online Features and Print. Philadelphia: Elsevier:439--80
  • Hull CJ, Van Beem HB, McLeod K, et al. A pharmacodynamic model for pancuronium. Br J Anaesth 1978;50:1113–23
  • Homer TD, Stanski DR. The effect of increasing age on thiopental disposition and anesthetic requirement. Anesthesiology 1985;62:714–24
  • Stanski DR, Maitre PO. Population pharmacokinetics and pharmacodynamics of thiopental: the effect of age revisited. Anesthesiology 1990;72:412–22
  • Buhrer M, Maitre PO, Crevoisier C, Stanski DR. Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam. Clin Pharmacol Ther 1992;48:555–67
  • Scott JC, Stanski DR. Decreased fentanyl-alfentanil dose requirement with increasing age: a pharmacodynamic basis. J Pharmacol Exp Ther 1987;240:159–66
  • Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology 1991;74:34–42
  • Donati F. Onset of action of relaxants. Can J Anaesth 1988;35:S52–8
  • Chan PL, Holford NH. Drug treatment effects on disease progression. Annu Rev Pharmacol Toxicol 2001;41:625–59
  • Post TM, Freijer JI, DeJongh J, Danhof M. Disease system analysis: basic disease progression models in degenerative disease. Pharm Res 2005;22:103–49
  • Gunaratna C. Drug metabolism and pharmacokinetics in drug discovery. A primer for bioanalytical chemists, part I. Curr Separ 2000;19:17--23
  • Stumpf WE. Drug localization and targeting with receptor microscopic autoradiography. J Pharmacol Toxicol Meth 2005;51:25–40
  • Yamashita F, Hashida M. Pharmacokinetic considerations for targeted drug delivery. Adv Drug Deliv Rev 2013;65:139–47
  • Saraf S, Ghosh A, Kaur CD, Saraf S. Novel modified nanosystem based lymphatic targeting. Res J Nanosci Nanotechnol 2011;1:60–74
  • Wang Y, Wang N, Wang J, et al. Delivering systems pharmacogenomics towards precision medicine through mathematics. Adv Drug Deliv Rev. Available from: http://dx.doi.org/10.1016/j.addr.2013.03.002 [last accessed 22 Mar 2013]
  • Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J 2007; 9:Article 15. http://www.aapsj.org [last accessed 11 Oct 2012]
  • Myers AC, Kovach JS, Vuk-Pavlovic S. Binding, internalization, and intracellular processing of protein ligands. Derivation of rate constants by computer modeling. J Biol Chem 1987;262:6494–9
  • Shankaran H, Resat H, Wiley HS. Cell surface receptors for signal transduction and ligand transport: a design principles study. PLoS Comput Biol 2007;3:e101. doi:10.1371/journal.pcbi.0030101
  • McVey Ward D, Kaplan J. The rate of internalization of different receptor-ligand complexes in alveolar macrophages is receptor-specific. Biochem J 1990;270:369–74
  • Suzuki H, Nakai D, Seita T, Sugiyama Y. Design of a drug delivery system for targeting based on pharmacokinetic consideration. Adv Drug Deliv Rev 1996;19:335–57
  • Siegel RA, MacGregor RD, Hunt CA. Comparison and critique of two models for regional drug delivery. J Pharmacokinet Biopharm 1991;19:363–74
  • Boddy AV, Aarons LJ. Pharmacokinetic and pharmacodynamic aspects of site-specific drug delivery. Adv Drug Deliv Rev 1989a;3:155–63
  • Boddy AV, Aarons LJ, Petrak K. Efficiency of drug targeting: steady-state considerations using a three-compartment model. Pharm Res 1989b;6:367–72
  • Gupta PK, Hung CT. Quantitative evaluation of targeted drug delivery systems. Int J Pharm 1989;56:217–26
  • Sugiyama Y, Kato Y. Pharmacokinetic aspects of peptide delivery and targeting: importance of receptor-mediated endocytosis. Drug Dev Ind Pharm 1994;20:591–614
  • Pyatak PS, Abuchowski A, Davis FF. Preparation of a polyethylene glycol: superoxide dismutase adduct and an examination of its blood circulation life and anti-inflammatory activity. Res Commun Chem Pathol Pharmacol 1980;29:113–27
  • Yokoyama M. Block copolymers as drug carriers. Crit Rev Ther Drug Carrier Syst 1992;9:213–48
  • Sugiyama Y, Kato Y. In vitro models of hepatic uptake: Methods to determine kinetic parameters for receptor-mediated hepatic uptake. In: Taylor MD, Amidon GL, eds. Peptide-based drug design: controlling transport and metabolism. Washington, DC: ACS Professional Reference Book, American Chemical Society; 1995:525–51
  • Bauer L. Applied clinical pharmacokinetics. New York: McGraw-Hill Edu; 2008
  • Nishikawa M, Takakura Y, Hashida M. Pharmacokinetic evaluation of polymeric carriers. Adv Drug Deliv Rev 1996;21:135–55
  • Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973;1:123–36
  • Bodor N, Farag HH, Brewster ME. Redox delivery for brain specific, sustained release of dopamine. Science 1983;221:65–7
  • Takakura Y, Mahato RI, Nishikawa M, Hashida M. Control of pharmacokinetic profiles of drug-macromolecule conjugates. Adv Drug Deliv Rev 1996a;19:377–99
  • Takakura Y, Fujita T, Hashida M, Sezaki H. Disposition characteristics of macromolecules in tumor-bearing mice. Pharm Res 1990;7:339–46
  • Takakura Y, Hashida M. Macromolecular carrier system for targeted drug delivery: pharmacokinetic considerations on biodistribution. Pharm Res 1996b;13:820–31
  • Leveque D, Wisnievski S, Jehl F. Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 2005;25:2327–43
  • Saga T, Neumann RD, Heya T, et al. Targeting cancer micrometastases with monoclonal antibodies: a binding site barrier. Proc Natl Acad Sci USA 1995;92:8999–9003
  • LoBuglio AF, Wheeler RH, Trang J, et al. Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci USA 1989;86:4220–4
  • Hu Q, Bally MB, Madden TD. Subcellular trafficking of antisense oligonucleotides and down-regulation of bcl-2 gene expression in human melanoma cells using a fusogenic liposome delivery system. Nucleic Acids Res 2002;30:3632–41
  • Juliano RL, Ming X, Nakagawa O. Cellular uptake and intracellular trafficking of antisense and siRNA oligonucleotides. Bioconjug Chem 2012;23:147–57
  • Paddison PJ, Hannon GJ. siRNAs and shRNAs: skeleton keys to the human genome. Curr Opin Mol Ther 2003;5:217–24
  • Jain KK. Neuroprotective agents. In: The handbook of neuroprotection. New York, Dordrecht, Heidelberg, London: Springer; 2011:25–139
  • Jeong JH, Park GT, Kim SH. Self-assembled and nanostructured siRNA delivery systems. Pharm Res 2011;28:2072–85
  • Dorsett Y, Tuschl T. siRNAs: applications in functional genomics and potential as therapeutics. Laboratory of RNA Molecular Biology, Rockefeller University; 2013
  • Laufer SD, Detzer A, Sczakiel G, Restle T. Selected strategies for the delivery of siRNA in vitro and in vivo. In: Erdmann VA, Barciszewski J, eds. RNA technologies and their applications, RNA technologies. Berlin Heidelberg: Springer-Verlag; 2010:29--58
  • Schiffelers RM, Ansari A, Xu J, et al. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucl Acids Res 2004;32:e149
  • Cejka D, Losert D, Wacheck V. Short interfering RNA (siRNA): tool or therapeutic? Clin Sci 2006;110:47–58
  • Won YW, Lim KS, Kim YH. Intracellular organelle-targeted non-viral gene delivery systems. J Control Release 2011;152:99–109
  • Agrawal S, Temsamani J, Tang JY. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci USA 1991;88:7595–9
  • Templin MV, Levin AA, Graham MJ, et al. Pharmacokinetic and toxicity profile of a phosphorothioate oligonucleotide following inhalation delivery to lung in mice. Antisense Nucleic Acid Drug Dev 2000;10:359–68
  • Agrawal S, Temsamani J, Galbraith W, Tang J. Pharmacokinetics of antisense oligonucleotides. Clin Pharmacokinet 1995;28:7–16
  • Yu RZ, Geary RS, Leeds JM, et al. Comparison of pharmacokinetics and tissue disposition of an antisense phosphorothioate oligonucleotide targeting human Haras mRNA in mouse and monkey. J Pharm Sci 2001;90:182–93
  • Parra-Guillen ZP, Gonzalez-Aseguinolaza G, et al. Gene therapy: a pharmacokinetic/pharmacodynamic modelling overview. Pharm Res 2010;27:1487–97
  • Schaffert D, Wagner E. Gene therapy progress and prospects: synthetic polymer-based systems. Gene Ther 2008;15:1131–8
  • Park J, Kim WJ. Current status of gene delivery: spotlight on nanomaterial-polymer hybrids. J Drug Target 2012;20:648–66
  • Hsu MCY, Uludag H. Nucleic-acid based gene therapeutics: delivery challenges and modular design of nonviral gene carriers and expression cassettes to overcome intracellular barriers for sustained targeted expression. J Drug Target 2012;20:301–28
  • Hirlekar R, Jagtap P, Kadam V. Advanced vectors for gene delivery. Curr Drug Ther 2011;6:251–62
  • Musacchio T, Navarro G, Torchilin VP. Molecular assemblies for siRNA delivery. J Drug Deliv Sci Tech 2012;22:5–16
  • Amiji MM. Nanotechnology, improved targeting delivery. Drug Deliv 2007;17:53–6. Available from: http://www.touchbriefings.com/pdf/2514/amiji.pdf [last accessed 11 Oct 2012]
  • St George JA. Gene therapy progress and prospects: adenoviral vectors. Gene Ther 2003;10:1135–41
  • Han S, Mahato RI, Sung YK, Kim SW. Development of biomaterials for gene therapy. Mol Ther 2000;2:302–17
  • Brown MD, Schatzlein AG, Uchegbu IF. Gene delivery with synthetic (non viral) carriers. Int J Pharm 2001;229:1–21
  • Belting M, Sandgren S, Wittrup A. Nuclear delivery of macromolecules: barriers and carriers. Adv Drug Deliv Rev 2005;57:505–27
  • Osaka G, Carey K, Cuthbertson A, et al. Pharmacokinetics, tissue distribution, and expression efficiency of plasmid P-33 DNA following intravenous administration of DNA/cationic lipid complexes in mice: use of a novel radionuclide approach. J Pharm Sci 1996;85:612–18
  • Yu L, Suh H, Koh JJ, Kim SW. Systemic administration of TerplexDNA system: pharmacokinetics and gene expression. Pharm Res 2001;18:1277–83
  • Nomura T, Nakajima S, Kawabata K, et al. Intratumoral pharmacokinetics and in vivo gene expression of naked plasmid DNA and its cationic liposome complexes after direct gene transfer. Cancer Res 1997;57:2681–6
  • Ledley TS, Ledley FD. Multicompartimental, numerical-model of cellular events in the pharmacokinetics of gene therapies. Hum Gene Ther 1994;5:679–91
  • Banks GA, Roselli RJ, Chen R, Giorgio TD. A model for the analysis of nonviral gene therapy. Gene Ther 2003;10:1766–75
  • Yamada Y, Kamiya H, Harashima H. Kinetic analysis of protein production after DNA transfection. Int J Pharm 2005;299:34–40
  • Moriguchi R, Kogure K, Harashima H. Non-linear pharmacodynamics in the transfection efficiency of a non-viral gene delivery system. Int J Pharm 2008;363:192–8
  • Berraondo P, Gonzalez-Aseguinolaza G, Troconiz IF. Semimechanistic pharmacodynamic modelling of gene expression and silencing processes. Eur J Pharm Sci 2009;37:418–26
  • Ruponen M, Arkko S, Urtti A, et al. Intracellular DNA release and elimination correlate poorly with transgene expression after non-viral transfection. J Contr Rel 2009;136:226–31
  • Simonson OE, Svahn MG, Törnquist E, et al. Bioplex technology: novel synthetic gene delivery pharmaceutical based on peptides anchored to nucleic acids. Curr Pharm Des 2005;11:3671–80
  • Oprea II. Gene therapy: new developments of non-viral vectors. Thesis, University of Medicine and Pharmacy, Cluj-Napoca (Supervisors: Leucuta SE, Smith CI); 2010. Available from: http://www.umfcluj.ro/index.php/en/educatie-uk/scoaladoctorala-uk [last accessed 12 Oct 2013]
  • Kuh HJ, Jang SH, Wientjes MG, Au JL. Computational model of intracellular pharmacokinetics of paclitaxel. J Pharmacol Exp Ther 2000;293:761–70
  • Beringer P, Huynh KM, Kriengkauykiat J, et al. Absolute bioavailability and intracellular pharmacokinetics of azithromycin in patients with cystic fibrosis. Antimicrob Agents Chemother 2005;49:5013–17
  • Bazzoli C, Jullien V, Le Tiec C, et al. Intracellular pharmacokinetics of antiretroviral drugs in hiv-infected patients, and their correlation with drug action. Clin Pharmacokinet 2010;49:17–45
  • Baheti G, Kiser JJ, Havens PL, Fletcher CV. Plasma and intracellular population pharmacokinetic analysis of tenofovir in hiv-1 infected patients. Antimicrob Agents Chemother 2011;55:5294–9
  • Phua KKL, Leong KW, Nair SK. Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format. J Contr Rel 2013;166:227–33
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46:3–26
  • Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci 2006;95:1238–57
  • Balaz S, Sturdik E, Augustin J. Subcellular distribution of compounds in biosystems. Bull Math Biol 1988;50:367–78
  • Zheng N. Cheminformatic and mechanistic study of drug subcellular transport/distribution Thesis, University of Michigan; 2011. Available from: http://deepblue.lib.umich.edu/bitstream/handle/2027.42/89626/nanzh_1.pdf?sequence=1 [last accessed 12 Oct 2013]
  • Rosania GR. Supertargeted chemistry: identifying relationships between molecular structures and their sub-cellular distribution. Curr Top Med Chem 2003;3:659–85
  • Zheng N. Cheminformatic and mechanistic study of drug subcellular transport/distribution. Curr Top Med Chem 2003;3:659–85
  • Olson KJ, Ahmadzadeh H, Arriaga EA. Within the cell: analytical techniques for subcellular analysis. Anal Bioanal Chem 2005;382:906–17
  • Dvorsky R, Balaz S, Sawchuk RJ. Kinetics of subcellular distribution of compounds in simple biosystems and its use in QSAR. J Theor Biol 1997;185:213–22

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.