|
|
|
Developing macromolecular therapeutics: the future
drug-of-choice |
| Huining HE1,Victor C. YANG1,Weibing DONG2,Junbo GONG2,Jingkang WANG2, |
| 1.Tianjin Key Laboratory
for Modern Drug Delivery and High Efficiency, Tianjin University,
Tianjin 300072, China;State Key Laboratory
of Chemical Engineering, Tianjin University, Tianjin 300072, China;School of Chemical Engineering,
Tianjin University, Tianjin 300072, China;Department of Pharmaceutical
Sciences, College of Pharmacy, University of Michigan, 428 Church
Street, Ann Arbor, MI 48109-1065, USA; 2.Tianjin Key Laboratory
for Modern Drug Delivery and High Efficiency, Tianjin University,
Tianjin 300072, China;State Key Laboratory
of Chemical Engineering, Tianjin University, Tianjin 300072, China;School of Chemical Engineering,
Tianjin University, Tianjin 300072, China; |
|
|
|
|
Abstract Macromolecular drugs including peptides, proteins, antibodies, polysaccharides and nucleic acids have been widely used for therapy of major diseases such as carcinoma and AIDS as well as cardiovascular and neurodegenerative disorders among other medical conditions. Due to their unmatched properties of high selectivity and efficiency, macromolecular drugs have been recognized as the drug-of-choice of the future. Since worldwide progress on macromolecular therapeutics still remains in the infant stage and is therefore wide open for equal-ground competition, R&D related to macromolecular drugs should be considered as the main point of focus in China in setting up its strategic plans in pharmaceutical development. In this article, research strategies and drug delivery approaches that should be adopted to enhance the therapeutic effects of macromolecular drugs are reviewed. In addition, comments concerning how to implement such strategies to excel from competition in this challenging research field, such as the design of innovative and highly effective delivery systems of macromolecular drugs with self-owned intellectual property rights, are provided.
|
|
Issue Date: 05 March 2010
|
|
|
Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Delivery Rev, 2002, 54: 631–651
doi: 10.1016/S0169-409X(02)00044-3
|
|
Dreher M R, Liu W, Michelich C R, Dewhirst M W, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetrationof macromolecular drug carriers. J NatlCancer Inst, 2006, 98: 335–344
|
|
Maeda H, Seymour L W, Miyamoto Y. Conjugates of anticancer agents and polymers: advantagesof macromolecular therapeutics in vivo. Bioconjugate Chem, 2002, 3: 351–362
doi: 10.1021/bc00017a001
|
|
Takakura Y, Hashida M. Macromolecular drug carriersystems in cancer chemotherapy: macromolecular prodrugs. Crit Rev in Oncol Hematol, 1995, 18: 207–231
doi: 10.1016/1040-8428(94)00131-C
|
|
Defoort J P, Nardelli B, Huang W, Ho D D, Tam J P. Macromolecular assemblage in the designof a synthetic AIDS vaccine. Proc NatlAcad Sci USA, 1992, 89: 3879–3883
doi: 10.1073/pnas.89.9.3879
|
|
Hamajima K, Bukawa H, Fukushima J, Kawamoto S, Kaneko T, Sekigawa K I, Tanaka S I, Tsukuda M, Okuda K. A macromolecular multicomponent peptide vaccine preparedusing the glutaraldehyde conjugation method with strong immunogenicityfor HIV-1. Clin Immunol Immunopathol, 1995, 77: 374–379
doi: 10.1006/clin.1995.1165
|
|
Greenberg S, Frishman W. Co-enzyme Q10: a new drugfor cardiovascular disease. J Clin Pharmacol, 1990, 30: 596–608
|
|
Torchilin V P. Targeting of drugs and drug carriers within the cardiovascular system. Adv Drug Delivery Rev, 1995, 17: 75–101
doi: 10.1016/0169-409X(95)00042-6
|
|
Chang C-T L, Liou H-Y, Tang H L, Sung H Y. Activation,purification and properties of beta-amylase from sweet potatoes (Ipomoeabatatas). Biotechnol Appl Biochem, 1996, 24: 13–18
|
|
Noda T, Furuta S, Suda I. Sweet potato [beta]-amylase immobilized on chitosan beadsand its application in the semi-continuous production of maltose. Carbohydr Polym, 2001, 44: 189–195
doi: 10.1016/S0144-8617(00)00226-5
|
|
Buchner J, Pastan I, Brinkmann U. A method for increasing the yield of properly foldedrecombinant fusion proteins: single-chain immunotoxins from renaturationof bacterial inclusion bodies. Anal Biochem, 1992, 205: 263–270
doi: 10.1016/0003-2697(92)90433-8
|
|
Chen C, Ridzon D A, Broomer A J, Zhou Z, Lee D H, Nguyen J T, Barbisin M, Xu N L, Mahuvakar V R, Andersen M R, Lao K Q, Livak K J, Guegler K J. Real-time quantificationof microRNAs by stem-loop RT-PCR. NuclAcids Res, 2005, 33: e179
doi: 10.1093/nar/gni178
|
|
Gibson U E, Heid C A, Williams P M. A novel method for real time quantitative RT-PCR. Genome Res, 1996, 6: 995–1001
doi: 10.1101/gr.6.10.995
|
|
Siebert P D, Chenchik A, Kellogg D E, Lukyanov K A, Lukyanov S A. An improved PCR method forwalking in uncloned genomic DNA. Nucl AcidsRes, 1995, 23: 1087–1088
doi: 10.1093/nar/23.6.1087
|
|
Gerrard A J, Hudson D L, Brownlee G G, Watt F M. Towardsgene therapy for haemophilia B using primary human keratinocytes. Nat Genet, 1993, 3: 180–183
doi: 10.1038/ng0293-180
|
|
Pipe S W. Coagulation factors with improved properties for hemophilia genetherapy. Semin Thromb Hemost, 2004, 30: 227–237
doi: 10.1055/s-2004-825636
|
|
Suh J S, Lee J Y, Choi Y S, Yu F, Yang V, Lee S J, Chung C P, Park Y J. Efficient labeling of mesenchymal stem cells using cellpermeable magnetic nanoparticles. BiochemBiophys Res Commun, 2009, 379: 669–675
doi: 10.1016/j.bbrc.2008.12.041
|
|
Allen T M, Cullis P R. Drug delivery systems: enteringthe mainstream. Science, 2004, 303: 1818–1822
doi: 10.1126/science.1095833
|
|
Creque H M, Langer R, Folkman J. One month of sustained release of insulin from a polymerimplant. Diabetes, 1980, 29: 37–40
doi: 10.2337/diabetes.29.1.37
|
|
Drummond D C, Meyer O, Hong K, Kirpotin D B, Papahadjopoulos D. Optimizing liposomes fordelivery of chemotherapeutic agents to solid tumors. Pharmacol Rev, 1999, 51: 691–744
|
|
Harrington K J, Lewanski C R, Stewart J S W. Liposomes as vehicles for targeted therapy of cancer.Part 1: Preclinical development. Clin Oncol, 2000, 12: 2–15
|
|
Lukyanov A N, Elbayoumi T A, Chakilam A R, Torchilin V P. Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomesmodified with anti-cancer antibody. J ControlledRelease, 2004, 100: 135–144
doi: 10.1016/j.jconrel.2004.08.007
|
|
Templeton N S, Lasic D D, Frederik P M, Strey H H, Roberts D D, Pavlakis G N. Improved DNA: liposome complexes for increased systemicdelivery and gene expression. Nat Biotech, 1997, 15: 647–652
doi: 10.1038/nbt0797-647
|
|
Barichello J M, Morishita M, Takayama K, Nagai T. Encapsulationof hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitationmethod. Drug Dev Ind Pharm, 1999, 25: 471–476
doi: 10.1081/DDC-100102197
|
|
Deamer D W, Barchfeld G L. Encapsulation of macromoleculesby lipid vesicles under simulated prebiotic conditions. J Mol Evol, 1982, 18: 203–206
doi: 10.1007/BF01733047
|
|
Grenha A, Seijo B, Remuñán-López C. Microencapsulated chitosannanoparticles for lung protein delivery. Eur J Pharm Sci, 25: 427–437
doi: 10.1016/j.ejps.2005.04.009
|
|
Radtchenko I L, Sukhorukov G B, Möhwald H. Incorporation of macromolecules into polyelectrolytemicro- and nanocapsules via surface controlled precipitation on colloidalparticles. Colloids SurfA, 2002, 202: 127–133
doi: 10.1016/S0927-7757(01)01104-9
|
|
Hariharan S, Bhardwaj V, Bala I, Sitterberg J, Bakowsky U, Ravi Kumar M. Design of estradiol loaded PLGA nanoparticulate formulations:a potential oral delivery system for hormone therapy. Pharm Res, 2006, 23: 184–195
doi: 10.1007/s11095-005-8418-y
|
|
Carino G P, Jacob J S, Mathiowitz E. Nanosphere based oral insulin delivery. J Controlled Release, 2000, 65: 261–269
doi: 10.1016/S0168-3659(99)00247-3
|
|
Lowman A M, Morishita M, Kajita M, Nagai T, Peppas N A. Oral delivery of insulin using pH-responsivecomplexation gels. J Pharm Sci, 1999, 88: 933–937
doi: 10.1021/js980337n
|
|
Liu X, Pettway G J, McCauley L K, Ma P X. Pulsatilerelease of parathyroid hormone from an implantable delivery system. Biomaterials, 2007, 28: 4124–4131
doi: 10.1016/j.biomaterials.2007.05.034
|
|
Song H, Liang J F, Yang V C. A prodrug approach for delivery of t-PA: constructionof the cationic t-PA prodrug by a recombinant method and preliminaryin vitro evaluation of the construct. ASAIOJ, 2000, 46: 663–668
doi: 10.1097/00002480-200011000-00005
|
|
Duncan R. Polymerconjugates for tumour targeting and intracytoplasmic delivery. TheEPR effect as a common gateway? PharmaceutSci Tech Today, 1999, 2: 441–449
doi: 10.1016/S1461-5347(99)00211-4
|
|
Maeda H. Theenhanced permeability and retention (EPR) effect in tumor vasculature:the key role of tumor-selective macromolecular drug targeting. Advances in Enzyme Regulation, 2001, 41: 189–207
doi: 10.1016/S0065-2571(00)00013-3
|
|
Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromoleculardrugs, including the EPR effect in solid tumor and clinical overviewof the prototype polymeric drug SMANCS. Journal of Controlled Release, 2001, 74: 47–61
doi: 10.1016/S0168-3659(01)00309-1
|
|
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeabilityand the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release, 2000, 65: 271–284
doi: 10.1016/S0168-3659(99)00248-5
|
|
Wu J, Akaike T, Hayashida K, Okamoto T, Okuyama A, Maeda H. Enhanced vascular permeability in solid tumor involvingperoxynitrite and matrix metalloproteinases. Cancer Science, 2001, 92: 439–451
doi: 10.1111/j.1349-7006.2001.tb01114.x
|
|
Ahmad I, Longenecker M, Samuel J, Allen T M. Antibody-targeteddelivery of doxorubicin entrapped in sterically stabilized liposomescan eradicate lung cancer in mice. CancerRes, 1993, 53: 1484–1488
|
|
Baselga J, Norton L, Albanell J, Kim Y M, Mendelsohn J. Recombinant humanized anti-HER2antibody (herceptinTM) enhances the antitumor activity of paclitaxeland doxorubicin against HER2/neu overexpressing human breast cancerxenografts. Cancer Res, 1998, 58: 2825–2831
|
|
Tardi P, Boman N, Cullis P. Liposomal doxorubicin. Journalof Drug Targeting, 1996, 4: 129–140
doi: 10.3109/10611869609015970
|
|
Yang H M, Reisfeld R A. Doxorubicin conjugated witha monoclonal antibody directed to a human melanoma-associated proteoglycansuppresses the growth of established tumor xenografts in nude mice. Proc Natl Acad Sci USA, 1988, 85: 1189–1193
doi: 10.1073/pnas.85.4.1189
|
|
Davis T A, Grillo-Lopez A J, White C A, McLaughlin P, Czuczman M S, Link B K, Maloney D G, Weaver R L, Rosenberg J, Levy R. Rituximab anti-CD20monoclonal antibody therapy in non-hodgkin's lymphoma: safety andefficacy of re-treatment. J Clin Oncol, 2000, 18: 3135–3143
|
|
Davis T A, White C A, Grillo-Lopez A J, Velasquez W S, Link B, Maloney D G, Dillman R O, Williams M E, Mohrbacher A, Weaver R, Dowden S, Levy R. Single-agentmonoclonal antibody efficacy in bulky non-hodgkin's lymphoma: resultsof a phase II trial of rituximab. J ClinOncol, 1999, 17: 1851–1857
|
|
Jazirehi A R, Bonavida B. Cellular and molecular signaltransduction pathways modulated by rituximab (rituxan, anti-CD20 mAb)in non-Hodgkin's lymphoma: implications in chemosensitization andtherapeutic intervention. Oncogene, 2005, 24: 2121–2143
doi: 10.1038/sj.onc.1208349
|
|
Maloney D G, Grillo-Lopez A J, White C A, Bodkin D, Schilder R J, Neidhart J A, Janakiraman N, Foon K A, Liles T M, Dallaire B K, Wey K, Royston I, Davis T, Levy R. IDEC-C2B8 (rituximab) anti-CD20 monoclonalantibody therapy in patients with relapsed low-grade non-Hodgkin'slymphoma. Blood, 1997, 90: 2188–2195
|
|
Witzig T E, Flinn I W, Gordon L I, Emmanouilides C, Czuczman M S, Saleh M N, Cripe L, Wiseman G, Olejnik T, Multani P S, White C A. Treatment with ibritumomab tiuxetan radioimmunotherapyin patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol, 2002, 20: 3262–3269
doi: 10.1200/JCO.2002.11.017
|
|
Gao X, Tao W, Lu W, Zhang Q, Zhang Y, Jiang X, Fu S. Lectin-conjugated PEG-PLAnanoparticles: preparation and brain delivery after intranasal administration. Biomaterials, 2006, 27: 3482–3490
doi: 10.1016/j.biomaterials.2006.01.038
|
|
Lassalle V, Ferreira M L. PLA nano- and microparticlesfor drug delivery: an overview of the methods of preparation. Macromolecular Bioscience, 2007, 7: 767–783
doi: 10.1002/mabi.200700022
|
|
Munier S, Messai I, Delair T, Verrier B, Ataman-Önal Y. Cationic PLAnanoparticles for DNA delivery: comparison of three surface polycationsfor DNA binding, protection and transfection properties. Colloids and Surfaces B: Biointerfaces, 2005, 43: 163–173
doi: 10.1016/j.colsurfb.2005.05.001
|
|
Elvassore N, Bertucco A, Caliceti P. Production of insulin-loaded poly(ethylene glycol)/poly(1-lactide)(PEG/PLA) nanoparticles by gas antisolvent techniques. J Pharm Sci, 2001, 90: 1628–1636
doi: 10.1002/jps.1113
|
|
Janes K A, Calvo P, Alonso M J. Polysaccharide colloidal particles as delivery systemsfor macromolecules. Adv Drug Delivery Rev, 2001, 47: 83–97
doi: 10.1016/S0169-409X(00)00123-X
|
|
Chertok B, David A E, Moffat B A, Yang V C. Substantiatingin vivo magnetic brain tumor targeting of cationic iron oxide nanocarriersvia adsorptive surface masking. Biomaterials, 2009, 30: 6780–6787
doi: 10.1016/j.biomaterials.2009.08.040
|
|
Huang M, Qiao Z, Miao F, Jia N, Shen H. Biofunctional magnetic nanoparticlesas contrast agents for magnetic resonance imaging of pancreas cancer. Microchimica Acta, 2009, 167: 27–34
doi: 10.1007/s00604-009-0210-y
|
|
Zhao M, Kircher M F, Josephson L, Weissleder R. Differential conjugation of tat peptide to superparamagnetic nanoparticlesand its effect on cellular uptake. BioconjugateChemistry, 2002, 13: 840–844
doi: 10.1021/bc0255236
|
|
Needham D, Dewhirst M W. The development and testingof a new temperature-sensitive drug delivery system for the treatmentof solid tumors. Adv Drug Delivery Rev, 2001, 53: 285–305
doi: 10.1016/S0169-409X(01)00233-2
|
|
Qiu Y, Park K. Environment-sensitive hydrogelsfor drug delivery. Adv Drug Delivery Rev, 2001, 53: 321–339
doi: 10.1016/S0169-409X(01)00203-4
|
|
Morçöl T, Nagappan P, Nerenbaum L, Mitchell A, Bell S J D. Calcium phosphate-PEG-insulin-casein(CAPIC) particles as oral delivery systems for insulin. International Journal of Pharmaceutics, 2004, 277: 91–97
doi: 10.1016/j.ijpharm.2003.07.015
|
|
Agnihotri S A, Mallikarjuna N N, Aminabhavi T M. Recent advances on chitosan-based micro- and nanoparticlesin drug delivery. Journal of ControlledRelease, 2004, 100: 5–28
doi: 10.1016/j.jconrel.2004.08.010
|
|
Ceh B, Winterhalter M, Frederik P M, Vallner J J, Lasic D D. Stealth® liposomes: fromtheory to product. Adv Drug Delivery Rev, 1997, 24: 165–177
doi: 10.1016/S0169-409X(96)00456-5
|
|
Moghimi S M, Szebeni J. Stealth liposomes and longcirculating nanoparticles: critical issues in pharmacokinetics, opsonizationand protein-binding properties. Progressin Lipid Research, 2003, 42: 463–478
doi: 10.1016/S0163-7827(03)00033-X
|
|
Gupta B, Levchenko T S, Torchilin V P. Intracellular delivery of large molecules and small particlesby cell-penetrating proteins and peptides. Adv Drug Delivery Rev, 2005, 57: 637–651
doi: 10.1016/j.addr.2004.10.007
|
|
Patel L, Zaro J, Shen W C. Cell penetrating peptides: intracellular pathways andpharmaceutical perspectives. PharmaceuticalResearch, 2007, 24: 1977–1992
doi: 10.1007/s11095-007-9303-7
|
|
Snyder E, Dowdy S. Cell penetrating peptidesin drug delivery. Pharmaceutical Research, 2004, 21: 389–393
doi: 10.1023/B:PHAM.0000019289.61978.f5
|
|
Tréhin R, Merkle H P. Chances and pitfalls of cellpenetrating peptides for cellular drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 2004, 58: 209–223
doi: 10.1016/j.ejpb.2004.02.018
|
|
Fawell S, Seery J, Daikh Y, Moore C, Chen L L, Pepinsky B, Barsoum J. Tat-mediated delivery ofheterologous proteins into cells. ProcNatl Acad Sci U.S.A, 1994, 91: 664–668
doi: 10.1073/pnas.91.2.664
|
|
Frankel A D, Pabo C O. Cellular uptake of the tatprotein from human immunodeficiency virus. Cell, 1988, 55: 1189–1193
doi: 10.1016/0092-8674(88)90263-2
|
|
Green M, Loewenstein P M. Autonomous functional domainsof chemically synthesized human immunodeficiency virus tat trans-activatorprotein. Cell, 1988, 55: 1179–1188
doi: 10.1016/0092-8674(88)90262-0
|
|
Derossi D, Joliot A H, Chassaing G, Prochiantz A. The third helix of the Antennapedia homeodomain translocates throughbiological membranes. Journal of BiologicalChemistry, 1994, 269: 10444–10450
|
|
Phelan A, Elliott G, O'Hare P. Intercellular delivery of functional p53 by the herpesvirusprotein VP22. Nat Biotech, 1998, 16: 440–443
doi: 10.1038/nbt0598-440
|
|
Byun Y, Chang L C, Lee L M, Han I S, Singh V K,Yang V C. Low molecular weight protamine: a potent but nontoxic antagonistto heparin/low molecular weight protamine. ASAIO Journal, 2000, 46: 435–439
doi: 10.1097/00002480-200007000-00013
|
|
Byun Y, Singh V K, Yang V C. Low molecular weight protamine: a potential nontoxicheparin antagonist. Thrombosis Research, 1999, 94: 53–61
doi: 10.1016/S0049-3848(98)00201-1
|
|
Chang L C, Lee H F, Yang Z, Yang V. Low molecularweight protamine (LMWP) as nontoxic heparin/low molecular weight heparinantidote (I): Preparation and characterization. The AAPS Journal, 2001, 3: 7–14
|
|
Chang L C, Liang J, Lee H F, Lee L, Yang V. Low molecular weight protamine (LMWP)as nontoxic heparin/low molecular weight heparin antidote (II): Invitro evaluation of efficacy and toxicity. The AAPS Journal, 2001, 3: 15–23
|
|
Chang L C, Wrobleski S, Wakefield T, Lee L, Yang V. Low molecular weight protamine as nontoxicheparin/low molecular weight heparin antidote (III): Preliminary invivo evaluation of efficacy and toxicity using a canine model. The AAPS Journal, 2001, 3: 24–31
|
|
Liang J F, Zhen L, Chang L C, Yang V C. A less toxicheparin antagonist—low molecular weight protamine. Biochemistry (Moscow), 2003, 68: 116–120
doi: 10.1023/A:1022109905487
|
|
Park Y J, Chang L C, Liang J F, Moon C, Chung C P, Yang V C. Nontoxic membrane translocation peptide from protamine, low molecularweight protamine (LMWP), for enhanced intracellular protein delivery:in vitro and in vivo study. FASEB J, 2005, 19: 1555–1557
|
|
Park Y J, Liang J F, Ko K S, Kim S W, Yang V C. Low molecular weight protamine as anefficient and nontoxic gene carrier: in vitro study. The Journal of Gene Medicine, 2003, 5: 700–711
doi: 10.1002/jgm.402
|
|
Schwarze S R, Ho A, Vocero-Akbani A, Dowdy S F. In vivo protein transduction: delivery of a biologically active proteininto the mouse. Science, 1999, 285: 1569–1572
doi: 10.1126/science.285.5433.1569
|
|
Kwon Y M, Li Y, Naik S, Liang J F, Huang Y, Park Y J, Yang V C. The ATTEMPTS delivery systemsfor macromolecular drugs. Expert Opinionon Drug Delivery, 2008, 5: 1255–1266
doi: 10.1517/17425240802498059
|
|
Li Y T, Kwon Y M, Spangrude G J, Liang J F, Chung H S, Park Y J, Yang V C. Preliminary in vivo evaluationof the protein transduction domain-modified ATTEMPTS approach in enhancingasparaginase therapy. Journal of BiomedicalMaterials Research Part A, 2009, 91A: 209–220
doi: 10.1002/jbm.a.32204
|
|
Liang J F, Li Y T, Song H, Park Y J, Naik S S, Yang V C. ATTEMPTS: a heparin/protamine-based delivery system for enzyme drugs. Journal of Controlled Release, 2002, 78: 67–79
doi: 10.1016/S0168-3659(01)00484-9
|
|
Park Y J, Liang J F, Song H, Li Y T, Naik S, Yang V C. ATTEMPTS: a heparin/protamine-based triggered release system forthe delivery of enzyme drugs without associated side-effects. Adv Drug Delivery Rev, 2003, 55: 251–265
doi: 10.1016/S0169-409X(02)00181-3
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|