Drug-loaded erythrocytes: On the road toward marketing approval

Drug Design, Development and Therapy

Volumn 10, Issue , 2016, Pages 665-676

  Bourgeaux, Vanessa ^a   Lanao, José M ^b   Bax, Bridget E ^c   Godfrin, Yann ^a  

^a ERYTECH PHARMA   (France)

^b UNIVERSITY OF SALAMANCA   (Spain)

^c ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Clinical use; Drug carrier; Encapsulation method; Industrial development; Red blood cell

Indexed keywords

ADENOSINE DEAMINASE; ASPARAGINASE; CELL PENETRATING PEPTIDE; DEXAMETHASONE; DEXAMETHASONE SODIUM PHOSPHATE; DEXTRAN SULFATE; DOCUSATE SODIUM; GLUTARALDEHYDE; PHYTIC ACID; POLYLYSINE; PRODRUG; THYMIDINE PHOSPHORYLASE; DIMETHYL SULFOXIDE; DRUG CARRIER;

ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC LEUKEMIA; ADENOSINE DEAMINASE DEFICIENCY; ALLERGIC REACTION; ARTIFICIAL KIDNEY; BIOREACTOR; BLOOD GROUP ABO SYSTEM; CELL SWELLING; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL BATCH RELEASE; CONTROLLED DRUG RELEASE; COST; CROHN DISEASE; CYSTIC FIBROSIS; DIALYSIS MEMBRANE; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG LOADED ERYTHROCYTE; DRUG MANUFACTURE; DRUG MARKETING; DRUG QUALITY; ELECTROPORATION; ENCAPSULATION; ENDOCYTOSIS; ERYTHROCYTE; ERYTHROCYTE FRAGILITY; GENERAL MEDICAL DEVICE; GOOD MANUFACTURING PRACTICE; HALF LIFE TIME; HEAT TREATMENT; HUMAN; HYPOTONIC SWELLING; IN VITRO SELECTION; IN VIVO STUDY; INDUSTRIALIZATION; MNGIE SYNDROME; MONOCYTE MACROPHAGE PRECURSOR CELL; NONHUMAN; OPSONIZATION; OSMOLALITY; OSMOSIS; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY CONTROL; QUALITY CONTROL PROCEDURES; RED CELL LOADER; REPRODUCIBILITY; REVIEW; SCALE UP; SEVERE COMBINED IMMUNODEFICIENCY; STORAGE; ULCERATIVE COLITIS; CHEMISTRY; MARKETING; METABOLISM; PHARMACEUTICS;

CELL-PENETRATING PEPTIDES; DIMETHYL SULFOXIDE; DRUG CARRIERS; ELECTROPORATION; ENDOCYTOSIS; ERYTHROCYTES; HUMANS; MARKETING; OSMOSIS; TECHNOLOGY, PHARMACEUTICAL;

EID: 84958582356     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S96470     Document Type: Review

References (91)

1. Pierige F, Serafini S, Rossi L, et al. Cell-based drug delivery. Adv Drug Deliv Rev. 2008;60(2):286–295.
2. Patel RP, Patel MJ, Patel NA. An overview of resealed erythrocyte drug delivery. J Pharm Res. 2009;2(6):1008–1012.
3. Millan CG, Marinero ML, Castaneda AZ, et al. Drug, enzyme and peptide delivery using erythrocytes as carriers. J Control Release. 2004;95(1):27–49.
4. Gothoskar AV. Resealed erythrocytes: a review. Pharmaceutical Technology [serial on the internet]; 2004;140–158. Available from: http://www.pharmtech.com. Accessed December 6, 2015.
5. Harisa GE, Ibrahim MF, Alanazi FK, et al. Application and safety of erythrocytes as a novel drug delivery system. Asian J Biochem. 2011;6:309–321.
6. Muzykantov VR. Drug delivery by red blood cells: vascular carriers designed by mother nature. Expert Opin Drug Deliv. 2010;7(4):403–427.
7. Gutierrez MC, Colino Gandarillas CI, Sayalero Marinero ML, et al. Cell-based drug-delivery platforms. Ther Deliv. 2012;3(1):25–41.
8. Domenech C, Thomas X, Chabaud S, et al. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial. Br J Haematol. 2011;153:58–65.
9. Tirupathi Rao K, Suria Prabha K, Muthu Prasanna P. Resealed erythrocytes: as a specified tool in novel drug delivery carrier system. Res J Pharm Biol Chem Sci. 2011;2(4):496–512.
10. Kitao T, Hattori K. Erythrocyte entrapment of daunomycin by amphotericin B without hemolysis. Cancer Res. 1980;40(4):1351–1353.
11. Li LH, Hensen ML, Zhao YL, et al. Electrofusion between heterogeneous-sized mammalian cells in a pellet: potential applications in drug delivery and hybridoma formation. Biophys J. 1996;71(1):479–486.
12. Nicolau C, Gersonde K. Incorporation of inositol hexaphosphate into intact red blood cells. I. Fusion of effector-containing lipid vesicles with erythrocytes. Naturwissenschaften. 1979;66(11):563–566.
13. Ginn FL, Hochstein P, Trump BF. Membrane alterations in hemolysis: internalization of plasmalemma induced by primaquine. Science. 1969;164(3881):843–845.
14. Harisa GE, Ibrahim MF, Alanazi FK. Characterization of human erythrocytes as potential carrier for pravastatin: an in vitro study. Int J Med Sci. 2011;8(3):222–230.
15. Talwar N, Jain NK. Erythrocyte based delivery system of primaquine: in vitro characterization. J Microencapsul. 1992;9(3):357–364.
16. Schrier SL, Junga I. Entry and distribution of chlorpromazine and vinblastine into human erythrocytes during endocytosis. Proc Soc Exp Biol Med. 1981;168(2):159–167.
17. Greenwalt TJ, Lau FO, Swierk EM, et al. Studies of erythrocyte membrane loss produced by amphipathic drugs and in vitro storage. Br J Haematol. 1978;39(4):551–557.
18. Kwon YM, Chung HS, Moon C, et al. L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL). J Control Release. 2009;139(3):182–189.
19. He H, Ye J, Wang Y, et al. Cell-penetrating peptides meditated encapsulation of protein therapeutics into intact red blood cells and its application. J Control Release. 2014;176:123–132.
20. Franco RS, Weiner M, Wagner K, et al. Incorporation of inositol hexaphosphate into red blood cells mediated by dimethyl sulfoxide. Life Sci. 1983;32(24):2763–2768.
21. Franco R, Barker R, Mayfield G, et al. The in vivo survival of human red cells with low oxygen affinity prepared by the osmotic pulse method of inositol hexaphosphate incorporation. Transfusion. 1990;30(3):196–200.
22. Mosca A, Paleari R, Russo V, et al. IHP entrapment into human erythrocytes: comparison between hypotonic dialysis and DMSO osmotic pulse. Adv Exp Med Biol. 1992;326:19–26.
23. Tsong TY. Electroporation of cell membranes. Biophys J. 1991;60(2):297–306.
24. Tsong TY, Kinosita K Jr. Use of voltage pulses for the pore opening and drug loading, and the subsequent resealing of red blood cells. Bibl Haematol. 1985;51:108–114.
25. Mitchell DH, James GT, Kruse CA. Bioactivity of electric field-pulsed human recombinant interleukin-2 and its encapsulation into erythrocyte carriers. Biotechnol Appl Biochem. 1990;12(3):264–275.
26. Lizano C, Sanz S, Luque J, et al. In vitro study of alcohol dehydrogenase and acetaldehyde dehydrogenase encapsulated into human erythrocytes by an electroporation procedure. Biochim Biophys Acta. 1998;1425(2):328–336.
27. Dong Q, Jin W. Monitoring diclofenac sodium in single human erythrocytes introduced by electroporation using capillary zone electrophoresis with electrochemical detection. Electrophoresis. 2001;22(13):2786–2792.
28. Dzekunov SM, Wang SH, Hanson DH, inventors; Maxcyte Inc., assignee. Apparatus and method for electroporation of biological samples. United States patent US 7186559. 2007 Mar 6.
29. Nicolau C, Bruggemann U, Mouneimne Y, Conrad Roux E, inventors; Cbr Laboratories Inc., assignee. Method and apparatus for encapsulation of biologically-active substances. Patent EP 1466968. 2006 Oct 4.
30. Bruggemann U, Roux EC, Hannig J, et al. Low-oxygen-affinity red cells produced in a large-volume, continuous-flow electroporation system. Transfusion. 1995;35(6):478–486.
31. Rechsteiner MC. Uptake of proteins by red blood cells. Exp Cell Res. 1975;93(2):487–492.
32. Hamidi M, Zarrin AH, Foroozesh M, et al. Preparation and in vitro evaluation of carrier erythrocytes for RES-targeted delivery of interferon-alpha 2b. Int J Pharm. 2007;341(1–2):125–133.
33. Hamidi M, Tajerzadeh H, Dehpour AR, et al. In vitro characterization of human intact erythrocytes loaded by enalaprilat. Drug Deliv. 2001;8(4):223–230.
34. Magnani M, Rossi L, D’ascenzo M, et al. Erythrocyte engineering for drug delivery and targeting. Biotechnol Appl Biochem. 1998;28(pt 1):1–6.
35. Rossi L, Serafini S, Pierigé F, et al. Erythrocytes as a controlled drug delivery system: clinical evidences. J Control Release. 2006;116(2):e43–e45.
36. Biagiotti S, Paoletti MF, Fraternale A, et al. Drug delivery by red blood cells. IUBMB Life. 2011;63(8):621–631.
37. Bax BE, Bain MD, Fairbanks LD, et al. In vitro and in vivo studies with human carrier erythrocytes loaded with polyethylene glycol-conjugated and native adenosine deaminase. Br J Haematol. 2000;109(3):549–554.
38. Bax BE, Bain MD, Fairbanks LD, et al. A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency. Eur J Haematol. 2007;79(4):338–348.
39. Godfrin Y, Bax BE. Enzyme bioreactors as drugs. Drugs Future. 2012;37(4):263–272.
40. Bourgeaux V, Hequet O, Campion Y, et al. Inositol hexaphosphate-loaded red blood cells prevent in vitro sickling. Transfusion. 2010;50(10):2176–2184.
41. Banz A, Cremel M, Rembert A, et al. In situ targeting of dendritic cells by antigen-loaded red blood cells: a novel approach to cancer immunotherapy. Vaccine. 2010;28(17):2965–2972.
42. Ropars C, Nicolau C, Chassaigne M, inventors; CNRS, Centre Hospitalier Regional De Tours, Studiengesellschaft Kohle mbH, assignees. Procédé et dispositif pour l’encapsulation dans les érythrocytes d’au moins une substance à activité biologique, notamment des effecteurs allostériques de l’hémoglobine et érythrocytes ainsi obtenus [Process and device for the encapsulation in erythrocytes of at least one biologically active substance, in particular hemoglobin allosteric effectors, and erythrocytes so obtained]. Patent EP 0101341. 1986 Nov 5. French.
43. Godfrin Y, inventor; Erytech Pharma, assignee. Lysis/resealing process and device for incorporating an active ingredient, in particular asparaginase or inositol hexaphosphate, in erythrocytes. Patent WO 2006016247. 2006 Feb 16.
44. Darghouth D, Koehl B, Heilier JF, et al. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis. Haematologica. 2011;96(12):1861–1865.
45. Bernhardt I, Llory JC. Red Cell Membrane Transport in Health and Disease. Berlin: Springer-Verlag; 2003.
46. Magnani M, Rossi L, Bagiotti S, Bianchi M, inventors. Drug delivery systems. United States patent US WO2010145849 A3. 2011 Dec 15.
47. Biagiotti S, Rossi L, Bianchi M, et al. Immunophilin-loaded erythrocytes as a new delivery strategy for immunosuppressive drugs. J Control Release. 2011;154(3):306–313.
48. Foroozesh M, Hamidi M, Zarrin A, et al. Preparation and in-vitro characterization of tramadol-loaded carrier erythrocytes for long-term intravenous delivery. J Pharm Pharmacol. 2011;63(3):322–332.
49. Tonetti M, Astroff AB, Satterfield W, et al. Pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde-treated canine erythrocytes. Am J Vet Res. 1991;52(10):1630–1635.
50. Tonetti M, Astroff B, Satterfield W, et al. Construction and characterization of adriamycin-loaded canine red blood cells as a potential slow delivery system. Biotechnol Appl Biochem. 1990;12(6):621–629.
51. DeLoach JR, Barton C. Glutaraldehyde-treated carrier erythrocytes for organ targeting of methotrexate in dogs. Am J Vet Res. 1981;42(11):1971–1974.
52. Baskurt OK. The role of spleen in suppressing the rheological alterations in circulating blood. Clin Hemorheol Microcirc. 1999;20(3):181–188.
53. Luo R, Mutukumaraswamy S, Venkatraman SS, et al. Engineering of erythrocyte-based drug carriers: control of protein release and bioactivity. J Mater Sci Mater Med. 2012;23(1):63–71.
54. Zocchi E, Guida L, Benatti U, et al. Hepatic or splenic targeting of carrier erythrocytes: a murine model. Biotechnol Appl Biochem. 1987;9(5):423–434.
55. Banz A, Cremel M, Mouvant A, et al. Tumor growth control using red blood cells as the antigen delivery system and poly(I: C). J Immunother. 2012;35(5):409–417.
56. Sprandel U, Way JL, editors. Erythrocytes as Drug Carriers in Medicine. New York, NY: Plenum Press; 1996.
57. Chiarantini L, Rossi L, Fraternale A, et al. Modulated red blood cell survival by membrane protein clustering. Mol Cell Biochem. 1995;144(1):53–59.
58. Magnani M, Rossi L, Brandi G, et al. Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies. Proc Natl Acad Sci U S A. 1992;89(14):6477–6481.
59. Magnani M, Casabianca A, Fraternale A, et al. Synthesis and targeted delivery of an azidothymidine homodinucleotide conferring protection to macrophages against retroviral infection. Proc Natl Acad Sci U S A. 1996;93(9):4403–4408.
60. Magnani M. In: Magnani M, editor. Erythrocyte Engineering for Drug Delivery and Targeting. New York, NY: Springer, Kluwer Academic/Plenum Publishers; 2003.
61. Hamidi M, Zarei N, Zarrin AH, et al. Preparation and in vitro characterization of carrier erythrocytes for vaccine delivery. Int J Pharm. 2007;338(1–2):70–78.
62. Polvani C, Gasparini A, Benatti U, et al. Murine red blood cells as efficient carriers of three bacterial antigens for the production of specific and neutralizing antibodies. Biotechnol Appl Biochem. 1991;14(3):347–356.
63. Magnani M, Chiarantini L, Vittoria E, et al. Red blood cells as an antigen-delivery system. Biotechnol Appl Biochem. 1992;16(2):188–194.
64. Cremel M, Guerin N, Horand F, et al. Red blood cells as innovative antigen carrier to induce specific immune tolerance. Int J Pharm. 2013;443(1–2):39–49.
65. Godfrin Y, Bertrand Y. L-asparaginase introduced into erythrocytes for the treatment of leukemia (ALL). Oncol News. 2006;1(1):2–4.
66. Mollër H, Oldenhof C. The active pharmaceutical ingredients starting material (APISM) and other materials in API manufacture. Drug Inf J. 1999;33:755–761.
67. European Medicines Agency (EMA). Reflection paper on clinical aspects related to tissue engineered products [report]. Report of Committee for Advanced Therapies (Draft). London; 2012. Report No 139870.
68. Burger SR. Design and operation of a current good manufacturing practices cell-engineering laboratory. Cytotherapy. 2000;2(2): 111–122.
69. Casaroli-Marano RP, Tabera J, Vilarrodona A, et al. Regulatory issues in cell-based therapy for clinical purposes. Dev Ophthalmol. 2014;53:189–200.
70. U.S. Department of Health and Human Services Food and Drug Administration. Guidance for Industry and FDA Staff: Minimal Manipulation of Structural Tissue Jurisdictional Update [guideline]. Silver Spring, MD: U.S. Department of Health and Human Services Food and Drug Administration; 2006.
71. National Institute of Health Science (NIHS). Guideline for Quality and Safety Assurance of Pharmaceuticals and Medical devices Based on Human Autologous Cells or Tissue. Research Triangle Park, NC: National Institute of Health Science (NIHS); 2008. [guideline in Japanese].
72. Sparrow RL, Sran A, Healey G, et al. In vitro measures of membrane changes reveal differences between red blood cells stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired study. Transfusion. 2014;54(3):560–568.
73. Sowemimo-Coker SO. Evaluation of an experimental filter designed for improving the quality of red blood cells (RBCs) during storage by simultaneously removing white blood cells and immunomodulators and improving RBC viscoelasticity and Band 3 proteins. Transfusion. 2014;54(3):592–601.
74. Brandenberger R, Burger S, Campbell A, et al. Cell therapy bioprocessing. Integrating process and product development for the next generation of biotherapeutics. BioProcess Int. 2011;9(S1):30–37.
75. Bessis M, Mohandas N, Feo C. Automated ektacytometry: a new method of measuring red cell deformability and red cell indices. Blood Cells. 1980;6(3):315–327.
76. Lamarre Y, Bourgeaux V, Pichon A, et al. Effect of inositol hexaphosphate-loaded red blood cells (RBCs) on the rheology of sickle RBCs. Transfusion. 2013;53(3):627–636.
77. Dacie JV, Lond MB, Vaughan JM, et al. The fragility of the red blood cells: its measurement and significance. J Pathol Bacteriol. 1938;46(2):341–356.
78. Guarnone R, Centenara E, Barosi G. Performance characteristics of Hemox-Analyzer for assessment of the hemoglobin dissociation curve. Haematologica. 1995;80(5):426–430.
79. Moroff G, Sohmer PR, Button LN. Proposed standardization of methods for determining the 24-hour survival of stored red cells. Transfusion. 1984;24(2):109–114.
80. International Committee for Standardization in Haematology. Recommended method for radioisotope red-cell survival studies. Br J Haematol. 1980;45(4):659–666.
81. Valeri CR, MacGregor H, Giorgio A, et al. Comparison of radioisotope methods and a nonradioisotope method to measure the RBC volume and RBC survival in the baboon. Transfusion. 2003;43(10):1366–1373.
82. Zeiler T, Muller J, Kretschmer V. Flow cytometric determination of survival time and 24-hour recovery of transfused Red blood cells. Transfus Med Hemother. 2003;30:14–19.
83. Boucher L, Chassaigne M, Ropars C. Internalization and distribution of inositol hexakisphosphate in red blood cells. Biotechnol Appl Biochem. 1996;24(pt 1):73–78.
84. Hunault-Berger M, Leguay T, Huguet F, et al. A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: the GRASPALL/GRAALL-SA2-2008 study. Am J Hematol. 2015;90(9):811–818.
85. Bourgeaux V, Aufradet E, Campion Y, et al. Efficacy of homologous inositol hexaphosphate-loaded red blood cells in sickle transgenic mice. Br J Haematol. 2012;157:357–369.
86. Rossi L, Serafini S, Cenerini L, et al. Erythrocyte-mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease. Biotechnol Appl Biochem. 2001;33(pt 2):85–89.
87. Rossi L, Castro M, D’Orio F, et al. Low doses of dexamethasone constantly delivered by autologous erythrocytes slow the progression of lung disease in cystic fibrosis patients. Blood Cells Mol Dis. 2004;33(1):57–63.
88. Castro M, Rossi L, Papadatou B, et al. Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease. J Pediatr Gastroenterol Nutr. 2007;44(4):423–426.
89. Menotta M, Biagiotti S, Bianchi M, et al. Dexamethasone partially rescues ataxia telangiectasia-mutated (ATM) deficiency in ataxia telangiectasia by promoting a shortened protein variant retaining kinase activity. J Biol Chem. 2012;287(49):41352–41363.
90. Chessa L, Leuzzi V, Plebani A, et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial. Orphanet J Rare Dis. 2014;9(1):5.
91. Leuzzi V, Micheli R, D’Agnano D, et al. Positive effect of erythrocyte-delivered dexamethasone in ataxia-telangiectasia. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e98.