Recent Progress in Drug Delivery Systems for Anticancer Agents

  • Kim, Chong-Kook (National Research Lab for Drug and Gene Delivery, College of Pharmacy, Seoul National University) ;
  • Lim, Soo-Jeong (National Research Lab for Drug and Gene Delivery, College of Pharmacy, Seoul National University)
  • Published : 2002.06.01

Abstract

Recent progress in understanding the molecular basis of cancer brought out new materials such as oligonucleotides, genes, peptides and proteins as a source of new anticancer agents. Due to their macromolecular properties, however, new strategies of delivery for them are required to achieve their full therapeutic efficacy in clinical setting. Development of improved dosage forms of currently marketed anticancer drugs can also enhance their therapeutic values. Currently developed delivery systems for anticancer agents include colloidal systems (liposomes, emulsions, nanoparticles and micelles), polymer implants and polymer conjugates. These delivery systems have been able to provide enhanced therapeutic activity and reduced toxicity of anticancer agents mainly by altering their pharmacokinetics and biodistribution. Furthermore, the identification of cell-specific receptor/antigens on cancer cells have brought the development of ligand- or antibody-bearing delivery systems which can be targeted to cancer cells by specific binding to receptors or antigens. They have exhibited specific and selective delivery of anticancer agents to cancer. As a consequence of extensive research, clinical development of anticancer agents utilizing various delivery systems is undergoing worldwide. New technologies and multidisciplinary expertise to develop advanced drug delivery systems, applicable to a wide range of anticancer agents, may eventually lead to an effective cancer therapy in the future.

Keywords

References

  1. Alakhov, V. Y., Moskaleva, E. Y., Batrakova, E. V. and Kabanov, A V., Hypersensitization of multidrug resistant human ovarian carcinoma cells by Pluronic P85 block copolymer. Bioconjug. Chem., 7, 209-216 (1996) https://doi.org/10.1021/bc950093n
  2. Bielinska, A., Kukowska-Latallo, J. F., Johnson, J., Tomalia, D. A. and Baker Jr., J. R., Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using starburst PAMAM dendrimers. Nucl. Acids. Res., 24, 2176-2182 (1996) https://doi.org/10.1093/nar/24.11.2176
  3. Brigger, I., chaminade, P., Marsaud, V., Appel, M., Besnard, M., Gurny, R., Renoir, M. and Couvreur, P., Tamoxifen encapsulation within polyethylene glycol-coated nanospheres. A new antiestrogen formulation. Int. J. Pharm., 214, 37-42 (2001) https://doi.org/10.1016/S0378-5173(00)00628-1
  4. Bue, P., Holmberg, A. R., Marquez, M., Westlin, J. E., Nilsson, S. and Malmstrom, P. U., Intravesical administration of EGF-dextran conjugates in patients with superficial bladder cancer. Eur. Urol., 38, 584-589 (2000) https://doi.org/10.1159/000020335
  5. Ceruti, M., Crosasso, P., Brusa, P., Arpicco, S., Dosia, F and Cattel, L., Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing water-soluble prodrugs of paclitaxel. J. Control. Release, 63, 141-153 (2000) https://doi.org/10.1016/S0168-3659(99)00198-4
  6. Chan, C. K., Hubner, S., Hu, W. and Jans, D. A, Mutual exclusivity of DNA binding and nuclear localization signal recognition by the yeast transcription factor GAL4: implications for nonviral DNA delivery. Gene Ther., 5, 1204-12(1998) https://doi.org/10.1038/sj.gt.3300708
  7. Chandy, T., Das, G. S. and Rao, G. H., 5-Fluorouracil-loaded chitosan coated polylactic acid microspheres as biodegradable drug carriers for cerebral tumours. J. Microencapsul., 17, 625-638 (2000) https://doi.org/10.1080/026520400417676
  8. Choi, Y., Kim, S. Y., Kim, S. H., Lee, K.-S., Kim, C. and Byun, Y., Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres. Int. J. Pharm., 215,67-81 (2001) https://doi.org/10.1016/S0378-5173(00)00676-1
  9. Ciaolfa, V. R, Zamai, M., Fiorino, E., Frigerio, E., Pellizzoni, C., d'Argy, R, Ghiglieri, A., Castelli, M. G., Farao, M., Pesenti, E., Gigli, M., Angelucci, F. and Suarato, A., Polymer-bound camptothecin: initial biodistribution and antitumor activity studies. J. Control. Release, 65,105-119 (2000) https://doi.org/10.1016/S0168-3659(99)00243-6
  10. Conover, C. D., Greenwald, R. B., Pendri, A. and Shum, K. L., Camptothecin delivery systems: the utility of amino acid spacers for the conjugation of camptothecin with polyethlene glycol to create prodrugs. Anticancer Drug Res., 14, 499-506 (1999)
  11. Constantinides, P. P., Lambert, K. J., Tustian, A. K., Schneider, B., Lalji, S., Ma, w., Wentzel, B., Kessler, D., Worah, D. and Quay, S. C., Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel. Pharm. Res., 17, 175-182 (2000) https://doi.org/10.1023/A:1007565230130
  12. Curnis, F, Sacchi, A., Borgna, L., Magni, F., Gasparri, A. and Corti, A., Enhancement of tumor necrosis factor antitumor immunotherapeutic properties by targeted delivery to amino-peptidase N (CD 13). Nature Biotech., 18, 1185-1190 (2000) https://doi.org/10.1038/81183
  13. Cuvier, C., Roblot-Treupel, L., Millot, J. M., Lizard, G., Chevillard, S., Manfait, M., Couvreur, P. and Poupon, M. F, Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance. Biochem. Pharmacol., 44,509-517 (1992) https://doi.org/10.1016/0006-2952(92)90443-M
  14. Delie, F, Berton, M., Allemann, E. and Gurny, R, Comparison of two methods of encapsulation of an oligonucleotide into poly(,-lactic acid) particles. lnt. J. Pharm., 214, 25-30 (2001) https://doi.org/10.1016/S0378-5173(00)00627-X
  15. De Rosa, F S., Marchetti, J. M., Thomazini, J. A., Tedesco, A. C. and Bentley, M. V., A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-amino-levulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy. J. Control. Release, 65, 359-366 (2000) https://doi.org/10.1016/S0168-3659(99)00213-8
  16. Denis-Mize, K. S., Dupuis, M., MacKichan, M. L., Singh, M., Doe, B., O'Hagan, D., Ulmer, J. B., Donnelly, J. J., McDonald, D. M. and Ott, G., Plasmid DNA adsorbed onto cationic microparticles mediates target gene expression and antigen presentation by dendritic cells. Gene Ther., 7, 2105-2112(2000) https://doi.org/10.1038/sj.gt.3301347
  17. Egilmez, N. K., Jong, Y. S., Sabel, M. S., Jacob, J. S., Mathiowitz, E. and Bankert, R. B., In situ tumor vaccination with interleukin-12-encapsulated biodegradable microspheres: Induction of tumor regression and potent antitumor immunity. Cancer Res., 60, 3832-3837 (2000)
  18. Elliott, G. and O'Hare, P, Intracellular trafficking and protein delivery by a herpesvirus structural protein. Cell, 88, 223-233 (1997) https://doi.org/10.1016/S0092-8674(00)81843-7
  19. Emerich, D. F, Winn, S. R., Snodgrass, P., LaFreniere, D., Agostino, M., Wiens, T., Xiong, H. and Bartus, R. T., Injectable chemotherapeutic microspheres and glioma II: Enhanced survival following implantation into deep inoperable tumors. Pharm. Res., 17, 776-781 (2000) https://doi.org/10.1023/A:1007591721877
  20. Ertl, B., Platzer, P., Wirth, M. and Gabor, F, Poly(D,L-lactic-coglycolic acid) microspheres for sustained delivery and stabilization of camptothecin. J. Control. Release, 61, 305-317(1999) https://doi.org/10.1016/S0168-3659(99)00122-4
  21. Etrych, T., Jellnkova, M., ihova, B. and Ulbrich, K., New HPMA copolymers containing doxorubicin bound via pH-sensitive linkage: synthesis and preliminary in vitro and in vivo biological properties. J. Control. Release, 73, 89-102 (2001) https://doi.org/10.1016/S0168-3659(01)00281-4
  22. Fan, H. and Dash, A. K., Effect of cross-linking on the in vitro release kinetics of doxorubicin from gelatin implants. Int. J. Pharm., 213, 103-116 (2001) https://doi.org/10.1016/S0378-5173(00)00651-7
  23. Finlay, I. G., Stewart, G. J., Pourgholami, M. H., Akhter, J. and Morris D. L., The use of lipiodol and medium chain triglyceride as delivery agents for hepatic arterial administration of 1,25-dihydroxyvitamin D3-A potential new treatment for hepato-cellular carcinoma. Anticancer Res., 20, 2705-2709 (2000)
  24. Fisher, K. D., Stallwood, Y, Green, N. K., Ulbrich, K., Mautner, V. and Seymour, L. W., Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther., 8, 341-348 (2001) https://doi.org/10.1038/sj.gt.3301389
  25. Forssen, E., The design and development of DaunoXome for solid tumor targeting in vivo. Adv. Drug Deliv. Rev., 24, 133-150(1997) https://doi.org/10.1016/S0169-409X(96)00453-X
  26. Fukushima, S., Kishimoto, S., Takeuchi, Y. and Fukushima, M., Preparation and evaluation of o/w type emulsions containing antitumor prostaglandin. Adv. Drug Deliv. Rev., 45, 65-75(2000) https://doi.org/10.1016/S0169-409X(00)00101-0
  27. Fundaro, A, Cavalli, R., Bargoni, A., Vighetto, D., Zara, G. P. and Gasco, M. R., Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: Pharmacokinetics and tissue distribution after i.v. administration to rats. Pharmacol. Res., 42,337-343 (2000) https://doi.org/10.1006/phrs.2000.0695
  28. Gabizon, A., Goren, D., Horowitz, A. T., Tzemach, D., Lossos, A and Siegal, T., Long-circulating liposomes for drug delivery in cancer therapy: a review of biodistribution studies in tumor-bearing animals. Adv. Drug Deliv. Rev., 24, 337-344 (1997) https://doi.org/10.1016/S0169-409X(96)00476-0
  29. Giles R. V.. Spiller, D. G., Grzybowski, J., Clark, R. E., Nicklin, P. and Tidd, D. M., Selecting optimal oligonucleotide com-position for maximal antisense effect following streptolysin O-mediated delivery into human leukaemia cells. Nucl. Acids Res., 26, 1567-1575 (1998) https://doi.org/10.1093/nar/26.7.1567
  30. Goren, D., Horowitz, A. T., Tzemach, D., Tarshish, M., Zalipsky, S. and Gabizon, A., Nuclear delivery of doxorubicin via folate-targeted Iiposomes with bypass of multidrug-resistarce efflux pump. Clin. Cancer Res., 6, 1949-1957 (2000)
  31. Greco, O. and Dachs, G. U., Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives. J. Cell. Physiol., 187, 22-36 (2001) https://doi.org/10.1002/1097-4652(2001)9999:9999<::AID-JCP1060>3.0.CO;2-H
  32. Gruenberq, J. and Maxfield, F. R., Membrane trasport in the endocytic pathway. Curr. Opn. Cell Biol., 7, 552-563 (1995) https://doi.org/10.1016/0955-0674(95)80013-1
  33. Han, J. H., Oh, Y. K, Kim, D. S. and Kim, C. K., Enhanced hepatocyte uptake and liver targeting of methotrexate using galactosylated albumin as a carrier. Int. J. Pharm., 188, 39-47(1999) https://doi.org/10.1016/S0378-5173(99)00206-9
  34. Harada, Y., Iwai, M., Tanaka, S., Okanoue, T., Kashima, K., Maruyama-Tabata, H., Hirai, H., Satoh, E., Imanishi, J. and Mazda, O., Highly efficient suicide gene expression in hepatocellular carcinoma cells by epstein-barr virus-based plasmid vectors combined with polyamidoamine dendrimer. Cancer Gene Ther., 7, 27-36 (2000) https://doi.org/10.1038/sj.cgt.7700079
  35. Harrington, K. J., Rowlinson-Busza, G., Uster, P. S. and Stewart, J. S., Pegylated liposome-encapsulated doxorubicin and cisplatin in the treatment of head and neck xenograft tumours. Cancer Chemother. Pharmacol., 46, 10-18 (2000)
  36. Higashi, S., Tabata, N., Kondo, K. H., Maeda, Y., Shimizu, M., Nakashima, T. and Setoguchi, T., Size of lipid microdroplets effects results of hepatic arterial chemotherapy with an anticancer agent in water-in-oil-in-water emulsion to hepatocellular carcinoma. J. Pharmacal. Exp. Ther., 289, 816-819(1999)
  37. Hong, R. L. and Tseng, Y. L., Phase I and pharmacokinetic study of a stable, polyethylene-glycolated liposomal doxorubicin in patients with solid tumors: the relation between pharmaco-kinetic property and toxicity. Cancer, 91, 1826-1833 (2001) https://doi.org/10.1002/1097-0142(20010501)91:9<1826::AID-CNCR1203>3.0.CO;2-J
  38. Huang, C. M., Wu, Y.-T. and Chen, S. T., Targeting delivery of paclitaxel into tumor cells via somatostatin receptor endocytosis. Chem. Biol. 7, 453-461 (2000) https://doi.org/10.1016/S1074-5521(00)00131-9
  39. Ichida, T, Kato, M., Hayakawa, A., Ito, S., Mori, S., Sato, T., Sugitani, S., Sato, H., Watanabe, M. and Asakura, H., Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced hepatocellular carcinoma. Cancer Chemother. Pharmacol., 33 Suppl, S74-78 (1994) https://doi.org/10.1007/BF00686672
  40. Ichinose, K., Tomiyama, N., Nakashima, M., Ohya, Y., Ichikawa, M., Ouchi, T. and Kanematsu, T, Antitumor activity of dextran derivatives immobilizing platinum complex (II). Anti-Cancer Drugs, 11, 33-38 (2000) https://doi.org/10.1097/00001813-200001000-00006
  41. Julyan, P. J., Seymour, L. W., Ferry, D. R., Daryani, S., Boivin, C. M., Doran, J., David, M., Anderson, D., Christodolou, C., Young, A. M., Hesselwood, S. and Kerr, D. J., Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine. J. Control. Release, 57, 281-290(1999) https://doi.org/10.1016/S0168-3659(98)00124-2
  42. Kaneda, Y., Virosomes: evolution of the liposome as a targeted drug delivery system. Adv. Drug Deliv. Rev., 43, 197-205 (2000) https://doi.org/10.1016/S0169-409X(00)00069-7
  43. Kanter, P. M., Klaich, G. M. and Bullard, G. A., Liposome encapsulated vincristine: Preclinical toxicologic and pharmacologic comparison with free vincristine and empty liposomes in mice, rats and dogs. Anticancer Drugs, 5, 579-590 (1994) https://doi.org/10.1097/00001813-199410000-00010
  44. Kataoka, K., Matsumoto, T., Yokoyama, M., Okano, T., Sakurai, Y., Fukushima, S., Okamoto, K. and Kwon, G. S., Doxorubicin-loaded poly(ethylene glycol)-poly(beta-benzyl-L-aspartate)copolymer micelles: their pharmaceutical characteristics and biological significance. J. Control. Release, 64, 143-153(2000) https://doi.org/10.1016/S0168-3659(99)00133-9
  45. Kim, C. K. and Han, J.-H., Lymphatic delivery and pharmacokinetics of methotrexate after intramuscular injection of differently charged liposome-entrapped methotrexate to rats. J. Microencapsul., 12, 437-446 (1995) https://doi.org/10.3109/02652049509087256
  46. Kim, C. K., Cho, Y. J. and Gao, Z. G., Preparation and evaluation of biphenyl dimethyl dicarboxylate microemulsions for oral delivery. J. Control. Release, 70, 149-155, 2001 https://doi.org/10.1016/S0168-3659(00)00343-6
  47. Kim, C. K., Choi, Y. J., Lim, S. J., Lee, M. G., Lee, S. H. and Hwang, S. J. Lymph nodes targeting and pharmacokinetics of $^{3}H$-methotrexate-encapsulated neutral large unilamellar vesicles and immunoliposomes. Int. J. Pharm., 98, 9-18(1993) https://doi.org/10.1016/0378-5173(93)90035-E
  48. Kim, C. K., Haider, K. H. and Lim, S. J., Gene medicine: a new field of molecular medicine. Arch. Pharm. Res., 24, 1-15 (2001) https://doi.org/10.1007/BF02976486
  49. Kim, C. K., Lee, M. K., Han, J. H. and Lee, B. J., Pharmacokinetics and tissue distribution of methotrexate after intravenous injection of differently charged liposome-entrapped methotrexate to rats. Int. J. Pharm., 108, 21-29, 1994 https://doi.org/10.1016/0378-5173(94)90412-X
  50. Koller-Lucae, S. K., Schott, H. and Schwendener, R. A., Low density lipoprotein and liposome mediated uptake and cytotoxic effect of N4-octadecyl-1-beta-D-arabinofuranosyl-cytosine in Daudi lymphoma cells. Br. J. Cancer, 80, 1542-1549(1999) https://doi.org/10.1038/sj.bjc.6690558
  51. Kondoh, M., Matsuyama, T., Suzuki, R., Mizuguchi, H., Nakanishi, T., Nakagawa, S., Tsutsumi, Y., Nakanishi, M., Sato, M. and Mayumi, T., Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester oligonucleotide encapsulated into fusogenic liposomes. Biol. Pharm. Bull., 23,1011-1013 (2000) https://doi.org/10.1248/bpb.23.1011
  52. Kong, G., Braun, R. D. and Dewhirst, M. W., Hyperthermia enables tumor-specific nanoparticle delivery: Effect of particle size. Cancer Res., 60,4440-4445 (2000)
  53. Koshkina, N. V., Kleinerman, E. S., Waidrep, C., Jia, S. F., Worth, L. L., Gilbert, B. E. and Knight, V., 9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice. Clin. Cancer Res., 6, 2876-2880(2000)
  54. Kreuter, J., Nanoparticulate systems for brain delivery of drugs. Adv. Drug Deliv. Rev., 47,65-81 (2001) https://doi.org/10.1016/S0169-409X(00)00122-8
  55. Leamon, C. P. and Low, P S., Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discov. Today, 6,44-51 (2001) https://doi.org/10.1016/S1359-6446(00)01594-4
  56. Leroux, J. C., Roux, E., LeGarrec, D., Hong, K. and Drummond, D.C., N-isopropylacrylamide copolymers for the preparation of pH-sensitive liposomes and polymeric micelles. J. Control. Release, 72, 71-84 (2001) https://doi.org/10.1016/S0168-3659(01)00263-2
  57. le Visage, C., Bernard, M., Michael, H. and Kam, L., Intravesical administration of paclitaxel encapsulated in poly(methylidene malonate 2.1.2) microparticles. Ann. Biomed. Eng., 28, S-21(2000)
  58. Lim, C. R., Kim, C.-K., Oh, K. H., Yuk, S. H. and Lee, H. B., The enhancement of liver targetability of $[^{3}H]$-methotrexate-galactosylated bovine serum albumin conjugate in mice. Int. J. Pharm., 132, 175-182 (1996) https://doi.org/10.1016/0378-5173(95)04381-0
  59. Lu, J. M., Peterson, C. M., Shiah, J. G., Gu, Z.-W, Peterson, C. A., Straight, R. C. and Kopeeek, J., Cooperativity between free and N-(2-hydroxypropyl) methacrylamide copolymer bound adriamycin and mesochlorin $e_{6}$ monothylene diamine induced photodynamic therapy in human epithelial ovarian carcinoma in vivo. Int. J. Oncol., 15,5-16 (1999)
  60. Lundberg, B., A submicron lipid emulsion coated with amphipathic polyethyelne glycol for parenteral administraiton of paclitaxel. J. Pharm. Pharmacol., 49,16-21 (1997) https://doi.org/10.1111/j.2042-7158.1997.tb06744.x
  61. Lundberg, B. B., Griffiths, G. and Hansen, H. J., Conjugation of an anti-B-cell lymphoma monoclonal antibody, LL2, to long-circulating drug-carrier lipid emulsions. J. Pharm Pharmacol. 51,1099-105 (1999) https://doi.org/10.1211/0022357991776787
  62. Maheshwari, A., Mahato, R. I., McGregor, J., Han, S. O., Samlowski, W. E., Park, J. S. and Kim, S. W., Soluble biodegradable polymer-based cytokine gene delivery for cancer treatment. Mol. Therapy, 2,121-130 (2000) https://doi.org/10.1006/mthe.2000.0105
  63. Martinez-Fong, D., Navarro-Quiroga, I., Ochoa, I., Alvarez-Maya, I., Meraz, M. A., Luna, J. and Arias-Montano, J. A., Neurotensin-SPDP-poly-L-lysine conjugate: a nonviral vector for targeted gene delivery to neural cells. Brain Res. Mol. Brain Res., 69, 249-262 (1999) https://doi.org/10.1016/S0169-328X(99)00114-X
  64. Miglietta, A., Cavalli, R., Bocca, C., Gabriel, L. and Gasco, M. R., Cellular uptake and cytotoxicity of solid lipid nanospheres (SLN) incorporating doxorubicin or paclitaxel. Int. J. Pharm. 210, 61-67 (2000) https://doi.org/10.1016/S0378-5173(00)00562-7
  65. Miller, M., Targeted cancer therapies attempt to hit the bull's-eye. J. Natl. Cancer Inst., 92, 1878-1879 (2000) https://doi.org/10.1093/jnci/92.23.1878
  66. Minko, T., Kopeekova, P.and Kopeeek, J., Efficacy of chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int. J. Cancer., 86, 108-117 (2000) https://doi.org/10.1002/(SICI)1097-0215(20000401)86:1<108::AID-IJC17>3.0.CO;2-8
  67. Miwa, A., Ishibe, A., Nakano, M., Yamahira, T., Itai, S., Jinno, S. and Kawahara, H., Development of novel chitosan derivatives as micellar carriers of taxol. Pharm. Res., 15, 1844-1850(1998) https://doi.org/10.1023/A:1011901921995
  68. Noguchi, Y., Wu, J., Duncan, R., Strohalm, J., Ulbrich, K., Akaike, T. and Maeda, H., Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn. J. Cancer Res., 89,307-314 (1998) https://doi.org/10.1111/j.1349-7006.1998.tb00563.x
  69. Oki, N., Anticancer therapy using glucuronate modified long-circulating liposomes. Adv. Drug Deliv. Rev., 40, 63-73(1999) https://doi.org/10.1016/S0169-409X(99)00040-X
  70. Pechar, M., Ulbrich, K., Subr, V., Seymour, L. W. and Schacht, E. H., Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin. Bioconjug. Chem., 11, 131-139(2000) https://doi.org/10.1021/bc990092l
  71. Plank, C., Oberhauser, B., Mechtler, K., Koch, C. and Wagner, E., The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer system. J. Biol. Chem., 269,12918-12924 (1994)
  72. Prasmickaite, L., Hogset, A. and Berg, K., Evaluation of different photosensitizers for use in photochemical gene transfection. Photochem. Photobiol., 73, 388-395 (2001) https://doi.org/10.1562/0031-8655(2001)073<0388:EODPFU>2.0.CO;2
  73. Provoda, C. J. and Lee, K. D., Bacterial pore-forming hemolysins and their use in the cytosolic delivery of macromolecules. Adv. Drug Deliv. Rev., 41,209-221 (2000) https://doi.org/10.1016/S0169-409X(99)00067-8
  74. Reed, D. S., Romero, P., Rimoldi, D., Cerottini, J. C., Schaack, J. and Jongeneel, C. V., Construction and characterization of a recombinant adenovirus directing expression of the MAGE-1 tumor-specific antigen. Int. J. Cancer., 72, 1045-1055 (1997) https://doi.org/10.1002/(SICI)1097-0215(19970917)72:6<1045::AID-IJC20>3.0.CO;2-2
  75. Robert, L., Peacock, G. G. and Lu, D. R., Targeted drug delivery for brain cancer treatment. J. Control. Release, 65, 31-41(2000) https://doi.org/10.1016/S0168-3659(99)00229-1
  76. Rosenkranz, A. A., Jans, D. A. and Sobolev, A. S., Targeted intracellular delivery of photosensitizers to enhance photodynamic efficiency. Immunol. Cell Biol., 78, 452-464 (2000) https://doi.org/10.1046/j.1440-1711.2000.00925.x
  77. Sato, Y., Yamauchi, N., Takahashi, M., Sasaki, K., Fukaura, J., Neda, H., Fujii, S., Hirayama, M., Itoh, Y., Koshita, Y., Kogawa, K., Kato, J., Sakamaki, S. and Niitsu, Y., In vivo gene delivery to tumor cells by transferrin-streptavidin-DNA conjugate. FASEB J., 14, 2108-2118 (2000) https://doi.org/10.1096/fj.99-1052com
  78. Siemens, D. R., Austin, J.C., Hedican, S. P., Tartaglia, J. and Ratliff, T. L., Viral vector delivery in solid-state vehicles: Gene expression in a murine prostate cancer model. J. Natl. Cancer Inst., 92, 403-412 (2000) https://doi.org/10.1093/jnci/92.5.403
  79. Skubitz, K. M. and Anderson, P. M., Inhalational interleukin-2 liposomes for pulmonary metastases: a phase I clinical trial. Anticancer Drugs, 11, 555-563 (2000) https://doi.org/10.1097/00001813-200008000-00006
  80. Sludden, J., Uchegbu, I. F. and Schatzlein, A. G., The encapsulation of bleomycin within chitosan based polymeric vesicles does not alter its biodistribution. J. Pharm. Pharmacol., 52, 377-382 (2000) https://doi.org/10.1211/0022357001774110
  81. Smith, J. P., Kanekal, S., Patawaran, M. B., Chen, J. Y., Jones, R. E., Orenberg, E. K. and Yu, N. Y., Drug retention and distribution after intratumoral chemotherapy with fluorouracil/epinephrine injectable gel in human pancreatic cancer xenografts. Cancer Chemother Pharmacol., 44, 267-274(1999) https://doi.org/10.1007/s002800050977
  82. stastny, M., Strohalm, J., Plocova, D., Ulbrich, K. and Oihova, B., A possibility to overcome P-glycoprotein (PGP)-mediated multidrug resistance by antibody-targeted drugs conjugated to HPMA copolymer carrier. Eur. J. Cancer, 35, 459-466(1999) https://doi.org/10.1016/S0959-8049(98)00373-6
  83. Straubinger, R. M., pH-sensitive liposomes for delivery of macromolecules into cytoplasm of culture cells. Methods Enzymol., 221, 361-376 (1993) https://doi.org/10.1016/0076-6879(93)21030-C
  84. Sugano, M., Egilmez, N. K., Yokota, S. J., Chen, F.-A., Harding, J., Huang, S. K. and Bankert, R. B., Antibody targeting of coxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice. Cancer Res., 60, 6942-6949 (2000)
  85. Torchilin, V. P., Polymer-coated long-circulating microparticulate pharmaceuticals. J Microencapsul., 15, 1-19 (1998) https://doi.org/10.3109/02652049809006831
  86. Trotta, M., Pattarino, F. and Gasco, M. R., Influence of counter ions on the skin permeation of methotrexate from water-oil microemulsions. Pharm. Acta Helv., 71,135-140 (1996) https://doi.org/10.1016/0031-6865(96)00003-9
  87. van Slooten, M. L., Boerman, O., Romoren, K., Kedar, E., Crommelin, D. J. A. and Storm, G., Liposomes as sustained release system for human interferon-g: biopharmaceutical aspects. Biochim. Biophys. Acta, 1530, 134-145 (2001) https://doi.org/10.1016/S1388-1981(00)00174-8
  88. Wang, C. C., Li, J., Teo, C. S. and Lee, T., The delivery of BCNU to brain tumors. J. Control. Release, 61, 21-41 (1999) https://doi.org/10.1016/S0168-3659(99)00098-X
  89. Ward, C. M., Acheson, N. and Seymour, L. W., Folic acid targeting of protein conjugates into ascites tumour cells from ovarian cancer patients. J. Drug Targeting, 8, 119-123(2000) https://doi.org/10.3109/10611860008996857
  90. Warren, L., Jardillier, J.-C., Malarska, A. and Akeli, M. G., Increased accumulation of drugs in multidrug resistant cells induced by liposomes. Cancer Res., 52, 3241-3245 (1992)
  91. Wong, B. K., Defeo-Jones, D., Jones, R. E., Garsky, V. M., Feng, D.-M., Oliff, A., Chiba, M., Ellis, J. D. and Lin, J. H., PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites. Drug Metab. Dispos., 29, 313-318 (2001)
  92. Woodle, M. C., Controlling liposomal blood clearance by surface-grafted polymers. Adv. Drug Deliv. Rev., 32, 139-152(1998) https://doi.org/10.1016/S0169-409X(97)00136-1
  93. Wyman, T B., Nicol, F., Zelphati, O., Scaria, P. V., Plank, C. and Szoka Jr., F. C., Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers. Biochemistry, 36, 3008-3017 (1997) https://doi.org/10.1021/bi9618474
  94. Yang, S., Zhy, J., Lu, Y., Liang, B. and Yang, C., Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm. Res., 16,751-757 (1999) https://doi.org/10.1023/A:1018888927852
  95. Yapp, D. T., Lloyd, D. K., Zhu, J. and Lehnert, S. M., Cisplatin delivery by biodegradable polymer implant is superior to systemic delivery by osmotic pump or i.p. injection in tumor-bearing mice. Anticancer Drugs, 9, 791-796 (1998) https://doi.org/10.1097/00001813-199810000-00008
  96. Yi, S. W., Kim, Y H., Kwon, I. C., Chung, J. W., Park, J. H., Choi, Y W. and Jeong, S. Y., Stable lipiodolized emulsions for hepatoma targeting and treatment by transcatheter arterial chemoembolization. J. Control. Release, 50,135-143(1998) https://doi.org/10.1016/S0168-3659(97)00127-2
  97. Yoo, H. S. and Park, T G., Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA-PEG block copolymer. J. Control. Release, 70, 63-70 (2001) https://doi.org/10.1016/S0168-3659(00)00340-0
  98. Zhang, X., Jackson, J. K. and Burt, H. M., Development of amphiphilic diblock copolymers as micellar carriers of taxol. Int. J. Pharm., 132, 195-206 (1996) https://doi.org/10.1016/0378-5173(95)04386-1
  99. Zou, Y., Ling, Y. H., Reddy, S., Priebe, W. and Perez-Soler, R., Effect of vesicle size and lipid composition on the in vivo tumor selectivity and toxicity of the non-cross-resistant anthracycline annamycin incorporated in liposomes. Int. J. Cancer, 61,666-671 (1995) https://doi.org/10.1002/ijc.2910610513