Nano-microbicides: Challenges in drug delivery, patient ethics and intellectual property in the war against HIV/AIDS

Advanced Drug Delivery Reviews

Volumn 62, Issue 4-5, 2010, Pages 532-546

  du Toit, Lisa C ^a   Pillay, Viness ^a   Choonara, Yahya E ^a  

^a UNIVERSITY OF THE WITWATERSRAND   (South Africa)

Author keywords

Dendrimer; Drug delivery systems; Human immunodeficiency virus; Intellectual property; Microbicide; Nano enabled; Nanoparticle; Patents

Indexed keywords

DEVELOPING WORLD; DRUG DELIVERY SYSTEM; HIV/AIDS; HUMAN IMMUNODEFICIENCY VIRUS; INNOVATIVE APPROACHES; MICROBICIDE; MICROBICIDES; MOLECULAR MODE; NANOCARRIERS; NANOMEDICINES; PARADIGM SHIFTS;

BIOLOGY; DENDRIMERS; DEVELOPING COUNTRIES; DISEASES; DRUG DELIVERY; INTERNATIONAL LAW; MEDICAL NANOTECHNOLOGY; MILITARY OPERATIONS; NANOPARTICLES; PATENTS AND INVENTIONS;

VIRUSES;

ANTIVIRUS AGENT; CYCLODEXTRIN; DENDRIMER; FULLERENE DERIVATIVE; GOLD NANOPARTICLE; LIPOSOME; MICROBICIDE; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NANOCARRIER; NANOMATERIAL; NANOPARTICLE; NANOVIRICIDE; NEVIRAPINE; PLACEBO; POLYSTYRENE; SDC 1721; SILVER NANOPARTICLE; SPL 2923; SPL 6195; SPL 7304; SPL 7320; UNCLASSIFIED DRUG; VIVAGEL;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIVIRAL ACTIVITY; BINDING SITE; CLINICAL TRIAL; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG EFFICACY; DRUG FORMULATION; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; ETHICS; FEASIBILITY STUDY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROGEN BOND; NANOPHARMACEUTICS; NANOTECHNOLOGY; NONHUMAN; PATENT; PHOTOSENSITIZATION; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; VIREMIA; VIRUS INFECTIVITY; VIRUS PARTICLE; VIRUS REPLICATION; VIRUS STRAIN; VIRUS TRANSMISSION;

ANTI-HIV AGENTS; DEVELOPING COUNTRIES; DRUG DELIVERY SYSTEMS; EXCIPIENTS; HIV INFECTIONS; HIV-1; HUMANS; INTELLECTUAL PROPERTY; NANOPARTICLES; NANOTECHNOLOGY; PATENTS AS TOPIC;

EID: 76849088626     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2009.11.022     Document Type: Review

References (109)

1. Grant R.M., Hamer D., Hope T., Johnston R., Michael J.L., Lederman M., Lieberman J., Miller C.J., Moore J.P., Mosier D.E., Richman D.D., Schooley R.T., Springer M.S., Veazey R.S., and Wainberg M.A. Whither or wither microbicides?. Science 321 (2008) 532-534
2. HIV/AIDS Epidemiological Surveillance Report for the WHO African Region (2005) Update, http://www.who.int/hiv/pub/epidemiology/hivinafrica2005e_web.pdf
3. Coplan P.M., Mitchnick M., and Rosenberg Z.F. Regulatory challenges in microbicide development. Science 25 (2004) 1911-1912
4. World Health Organization. Microbicides (2009) www.who.int/hiv/topics/microbicides/microbicides/en/
5. Elias C.J., and Coggins C. Female-controlled methods to prevent sexual transmission of HIV. AIDS 10 (1996) s43-s51
6. Eng T.R., and Butler W.T. The hidden epidemic: confronting sexually transmitted diseases (1997), National Academy Press, Washington, D.C
7. Rosenthal S.L., Cohen S.S., and Stanberry L.R. Topical microbicides: current status and research considerations for adolescent girls. Sex. Transm. Dis. 25 (1998) 368-377
8. Stein Z.A. HIV prevention: the need for methods women can use. Am. J. Public Health 80 (1990) 460-462
9. Bourne N., Stanberry L.R., Kern E.R., Holan G., Matthews B., and Bernstein D.I. Dendrimers, a new class of candidate microbicides with activity against herpes simplex virus infection. Antimicrob. Agents Chemother. 44 (2000) 2471-2474
10. Mitchell S. HIV Microbicides Gaining Pharma's Interest (February 1 2006), United Press International UPI Senior Medical Correspondent
11. Watts C., and Vickerman P. IDU Microbicide Ver 1: a model used to explore the impact of a microbicide intervention amongst intravenous drug users. AIDS 15 (2001) S43
12. Forster M.J., Mulloy B., and Nermut M.V. Molecular modelling study of HIV p17gag (MA) protein shell utilising data from electron microscopy and X-ray crystallography. J. Mol. Biol. 298 (2000) 841-857
13. Elechiguerra J., Burt J.L., Morones J.R., Camacho-Bragado A., Gao X., Lara H.H., and Jose Yacaman M.J. Interaction of silver nanoparticles with HIV-1. Nanobiotechnology 3 (2005) 1-10
14. Arthur L.O., Bess J., Sowder R., Benveniste R., Mann D., Chermann J., and Henderson L. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science 258 (1992) 1935-1938
15. Leonard C., Spellman M., Riddle L., Harris R., Thomas J., and Gregory T. Assignment of intrachain disulfide bonds and characterisation of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J. Biol. Chem. 265 (1990) 10373-10382
16. Lederman M.M., Veazey R.S., Offord R., Mosier D.E., Dufour J., Mefford M., Piatak Jr. M., Lifson J.D., Salkowitz J.R., Rodriguez B., Blauvelt A., and Hartley O. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 306 (2004) 485-487
17. Stone A., and Microbicides A. new approach to preventing HIV and other sexually transmitted infections. Nat. Rev. Drug Discov. 1 (2002) 977-985
18. Shattock R.J., and Moore J.P. Inhibiting sexual transmission of HIV-1 infection. Nat. Rev. Microbiol. 1 (2003) 25-34
19. 89.6PD in vitro and in vivo. AIDS 15 (2001) 1563-1568
20. Microbicides Development Programme Update, www.mdp.mrc.ac.uk/downloads/MDP_statement_14Feb08_v1[1].2_FINAL.pdf (2008).
21. van de Wijgert J.H., and Shattock R.J. Vaginal microbicides: moving ahead after an unexpected setback. AIDS 21 (2007) 2369-2376
22. Hillier S.L., Moench T., Shattock R., Black R., Reichelderfer P., et al. In vitro and in vivo: the story of nonoxynol 9. J. Acquir. Immune Defic. Syndr. 39 (2005) 1-8
23. Feldblum P.J., Adeiga A., Bakare R., Wevill S., Lendvay A., Obadaki F., Onikepe Olayemi M., Wang L., Nanada K., and Rountree W. SAVVY Vaginal Gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria. PLoS One 3 (2008) e1474
24. Moulard M., Lortat-Jacob H., Mondor I., Roca G., Wyatt R., Sodroski J., Zhao L., Olsen W., Kwong P.D., and Sattentau Q.J. Selective interaction of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120. J. Virol. 74 (2000) 1948-1960
25. Shattock R.J., and Doms R.W. AIDS models: microbicides could learn from vaccines. Nat. Med. 8 (2002) 425
26. Tao W., Richards C., and Hamer D. Enhancement of HIV Infection by cellulose sulphate. AIDS Res. Hum. Retrovir. 24 (2008) 1-5
27. Flexner C., Baarditch-Crovo P.A., Kornhauser D.M., Farzadegan H., Nerhood L.J., Chaisson R.E., Bell K.M., Lorentsen K.J., Hendrix C.W., and Petty B.G. Pharmacokinetics, toxicity, and activity of intravenous dextran sulphate in human immunodeficiency virus infection. Antimicrob. Agents Chemother. 35 (1991) 2544-2550
28. Meylan P.R., Kornbluth R.S., Zbinden I., and Richman D.D. Influence of host cell type and V3 loop of the surface glycoprotein susceptibility of human immunodeficiency virus type 1 to polyanion compounds. Antimicrob. Agents Chemother. 38 (1994) 2910-2916
29. News Release, University of Toronto, Joint Centre for Bioethics, 31 March 2005.
30. Mathiowitz E., Chickering D., Jacob J.S., and Santos C. Bioadhesive drug delivery systems. In: Mathiowitz E. (Ed). Encyclopedia of Controlled Drug Delivery vol. 1 (1999), Wiley, New York 9-44
31. Vasir J.K., Tambwekar K., and Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int. J. Pharm. 255 (2003) 13-32
32. ETC Group. Development Dossier: An Introduction to Nano-scale Technologies and the Implications for the Global South, produced by the United Nations Non-Governmental Liaison Service (NGLS), Geneva, Switzerland (2008) 1-98
33. R. Bawa, Nanotechnology patents and challenges, ipFrontline.com (2004).
34. Tomalia D.A. Birth of a new macromolecular architecture: dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry. Prog. Polym. Sci. 30 (2005) 294-324
35. Anderson P.W. More is different. Science 177 (1972) 393-396
36. European Science Foundation. Nanomedicine, an ESF - European Medical Research Councils (EMRC) Forward Look Report (2005)
37. Barker T.F., Fatehi L., Lesnick M.T., Mealey T.J., and Raimond R.R. Nanotechnology and the poor: opportunities and risks for developing countries. In: Allhof F., and Lin P. (Eds). Nanotechnology and Society: Current and Emerging Ethical Issues (2008), Springer, Netherlands 243-263
38. Bowman M.-C., Ballard T.E., Ackerson C.J., Feldheim D.L., Margolis D.M., and Melander C. Inhibition of HIV fusion with multivalent gold nanoparticles. J. Am. Chem. Soc. 130 (2008) 6896-6897
39. Mammen M., Choi S.K., and Whitesides G.M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem., Int. Ed. Engl. 37 (1998) 2755-2794
40. Caruthers S.D., Wickline S.A., and Lanza G.M. Nanotechnological applications in medicine. Curr. Opin. Biotechnol. 18 (2007) 26-30
41. Gorelik J., Shevchuk A., Ramalho M., Elliot M., Lei C., Higgins C.F., Lab M.J., Klenerman D., Krauzewicz N., and Korchev Y. Scanning surface confocal microscopy for simultaneous topographical and fluorescence imaging: application to single virus-like particle entry into a cell. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 16018-16023
42. Shevchuk A.I., Hobson P., Lab M.J., Klenerman D., Krauzewicz N., and Korchev Y.E. Imaging single virus particles on the surface of cell membranes by high-resolution scanning surface confocal microscopy. Biophys. J. 94 (2008) 4089-4094
43. M.J. Yacaman, J.L. Elechiquerra, H.H. Lara, J.L. Burt, Protein-noble metal nanoparticles, US Patent Application 20060115495.
44. Role of nanotechnology in developing antiviral agents, extract from report on 'Antiviral therapeutics - technologies, markets and companies', Jain PharmaBiotech, May 2009.
45. Jang W.-D., Kamruzzaman Selim K.M., Lee C.-H., and Kang I.-K. Bioinspired application of dendrimers: from bio-mimicry to biomedical applications. Prog. Polym. Sci. 34 (2009) 1-23
46. Tomalia D.A., Baker H., Dewald J., Hall M., Kallos G., Martin S., Roeck J., Ryder J., and Smith P. A new class of polymers: starburst-dendritic macromolecules. Polym. J. 17 (1985) 117-132
47. Bosman A.W., Janssen H.M., and Meijer E.W. About dendrimers: structure, physical properties, and applications. Chem. Rev. 99 (1999) 1665-1688
48. McCarthy T.D., Karellas P., Henderson S.A., Giannis M., O'Keefe D.F., Heery G., Paull J.R.A., Matthews B.R., and Holan G. Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention. Mol. Pharmacol. 2 (2005) 312-318
49. Marx V. Poised to branch out. Nat. Biotechnol. 26 (2008) 729-732
50. Barnard D.L., Sidwell R.W., Gage T.L., Okleberry K.M., Matthews B., and Holan G. Anti-respiratory syncytial virus activity of dendrimer polyanions. Antivir. Res. 34 (1997) A88
51. Witrouw M., Pannecouque C., Mathews B., Schols D., Andrei G., Snoeck R., Neyts J., Leyssen P., Desmyter J., Raff J., De Clercq E., and Holan G. Dendrimers inhibit the replication of human immunodeficiency virus by a dual mechanism of action. Antivir. Res. 41 (1999) A25
52. B.R. Matthews, G. Holan, Antiviral dendrimers, US Patent No. 6 190 650, 2001.
53. Luscher-Mattli M. Polyanions as a lost chance in the fight against HIV and other virus diseases?. Antivir. Chem. Chemother. 11 (2000) 249-259
54. Starpharma Info Centre, www.starpharma.com/info-centre.asp.
55. Mashino T., Shimotohno K., Ikegami N., Nishikawa D., Okuda K., Takahashi K., Nakamura S., and Mochizuki M. Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg. Med. Chem. Lett. 15 (2005) 1107-1109
56. Tang Y.J., Ashcroft J.M., Chen D., Min G., Kim C.-H., Murkhejee B., Larabell C., Keasling J.D., and Chen F.F. Charge-associated effects of fullerene derivatives on microbial structural integrity and central metabolism. Nano Lett. 7 (2007) 754-760
57. Marcorin G.L., Da Ros T., and Castellano S. Design and synthesis of novel [60] fullerene derivatives as potential HIV aspartic protease inhibitors. Org. Lett. 2 (2000) 3955-3958
58. Bakry R., Vallant R.M., Najam-ul-Haq M., Rainer M., Szabo Z., Huck C.W., and Bonn G.K. Medicinal applications of fullerenes. Int. J. Nanomedicine 2 (2007) 639-649
59. Marchesan S., Da Ros T., Spalluto G., Balzarini J., and Prato M. Anti-HIV properties of cationic fullerene derivatives. Bioorg. Med. Chem. Lett. 15 (2005) 3615-3618
60. Friedman S.H., Ganapathi P.S., Rubin Y., and Kenyon G.L. J. Med. Chem. 41 (1998) 2424
61. Zhu Z., Schuster D.I., and Tuckerman M.E. Molecular dynamics study of the connection between flap closing and binding of fullerene-based inhibitors of the HIV-1 protease. Biochemistry 42 (2003) 1326-1333
62. Bosi S., Da Ros T., Spalluto G., Balzarini J., and Prato M. Synthesis and anti-HIV properties of new water-soluble bis-functionalized [60]fullerene derivatives. Bioorg. Med. Chem. Lett. 13 (2003) 4437
63. Burlaka A.P., Sidorik Y.P., Prylutska S.V., Matyshevska O.P., Golub O.A., and Scharff P. Catalytic system of the reactive oxygen species on the C60 fullerene basis. Exp. Oncol. 26 (2004) 326-327
64. Sayes C.M., Fortner J.D., Guo W., Lyon D., Boyd A.M., Ausman K.D., Tao Y.J., Sitharaman B., Wilson L.J., Hughes J.B., West J.L., and Colvin V.L. The differential cytotoxicity of water-soluble fullerenes. Nano Lett. 4 (2004) 1881-1887
65. Tegos G.P., Demidova T.N., Arcila-Lopez D., Lee H., Wharton T., Gali H., and Hamblin M.R. Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem. Biol. 12 (2005) 1127-1135
66. Nanotechnology-based targeted antiviral therapeutics, http://www.nanoviricides.com/index.html.
67. A. Schuon, Positive Initial Results Pave the Way for Definitive Follow-Up Studies. Anti-HIV nanoviricide drug candidate demonstrates significant therapeutic efficacy in animal trials, Posted 5 May 2008, Nanotechnology Now, http://www.nanotech-now.com/news.cgi?story_id=29215.
68. Yang H., Parniak M., Isaacs C., Hillier S., and Rohan L. Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781. AAPS J. 10 (2008) 606-613
69. Barbaro G., Scozzafava A., Mastrolorenzo A., and Supuran C.T. Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Curr. Pharm. Des. 11 (2005) 1805-1843
70. Mintek Annual Report, 2005: Technical review.
71. http://www.engineeringnews.co.za/eng/news/breaking/?show=67605.
72. Gold Bulletin (2005) www.goldbulletin.org
73. Cho K., Park J., Osaka T., and Park S. The study of antimicrobial activity and preservative effects of nanosilver ingredient. Electrochim. Acta 51 (2005) 956-960
74. Pal S., Tak Y.K., and Song J.M. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 73 (2007) 1712-1720
75. Akagi T., Kawamura M., Ueno M., Hiraishi K., Adachi M., Serizawa T., Akashi M., and Baba M. Mucosal immunization with inactivated HIV-1-capturing nanospheres induces a significant HIV-1-specific vaginal antibody response in mice. J. Med. Virol. 69 (2003) 163-172
76. Hayakawa T., Kawamura M., Okamoto M., Baba M., Niikawa T., Satoshi T., Serizawa T., and Akashi M. Concanavalin A-immobilized polystyrene nanospheres capture HIV-1 virions and gp120: potential approach towards prevention of viral transmission. J. Med. Virol. 56 (1998) 327-331
77. P.F. Kiser, D.F. Katz, R.J. Stewart, Bioresponsive polymer system for delivery of microbicides, United States Patent Application 20070166382.
78. P.F. Kiser. A molecular condom against AIDS. http://unews.utah.edu/p/?r=111706-2, 1-3 (2006).
79. Ahuja A., Khar R.K., and Ali J. Mucoadhesive drug delivery systems. Drug Dev. Ind. Pharm. 23 (1997) 489-515
80. Ghezzo E., Benedetti L., Rochira N., Biviano F., and Callegaro L. Hyaluronane derivative microsphere as NGF delivery device: preparation methods and in vitro release characterisation. Int. J. Pharm. 87 (1992) 21-29
81. Patel J. Bioadhesive microspheres and their pharmaceutical applications. Drug Del. Tech. 7 (2007) 54-61
82. Richardson J.L., Whetstone J., Fisher N.F., Watts P., Farraj N.F., Hinchcliffe M., Benedetti L., and Illum L. Gamma scintigraphy as a novel method to study the distribution and retention of a bioadhesive vaginal delivery system in sheep. J. Control. Release 42 (1996) 133-142
83. Richardson J.L., and Armstrong T.I. Vaginal delivery of calcitonin by hyaluronic acid formulations. In: Mathiowitz E., Chickering D.E., and Lehr C.M. (Eds). Bioadhesive Drug-Delivery Systems - Fundamentals, Novel Approaches and Development '98 (1999), Marcel Dekker, New York 563-599
84. A. Greiner, T. Rocker, Polyethylenimine nanoparticle-containing microbicidal electrospun polymer fibers for textile applications, WO Application 2008/049250.
85. Pavelić Z., Skalko-Basnet N., and Jalsenjak I. Liposomes containing drugs for treatment of vaginal infections. Eur. J. Pharm. Sci. 8 (1999) 345-351
86. Ndesendo V.M.K., Pillay V., Choonara Y.E., Buchmann E., Bayever D.N., and Meyer L.C.R. A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV/AIDS and prevention of sexually transmitted infections. AAPS PharmSciTech 9 (2008) 205-210
87. Cristofaro P., and Ramratnam B. Prevention Strategies: Vaccines and Microbicides 12th Conference on Retrovirus and Opportunistic Infections. Boston, USA (2005) 22-25
88. Phillips D.M., Sudol K.M., Taylor C.L., Guichard L., Elsen R., and Maguire R.A. Lubricants containing N-9 may enhance rectal transmission of HIV and other STIs. Contraception 70 (2004) 107-110
89. Mnyusiwalla A., Daar A.S., and Singer P.A. "Mind the gap": science and ethics in nanotechnology. Nanotechnology 14 (2003) R9-R13
90. Faunce T.A. Nanotherapeutics: new challenges for safety and cost-effectiveness regulation in Australia. Nanotechnology MJA 186 (2007) 189-191
91. Linkov I., Satterstrom F.K., and Corey L.M. Nanotoxicology and nanomedicine: making hard decisions. Nanomed. Nanotech. Biol. Med. 4 (2008) 167-171
92. Aitken R.J., Creely K.S., and Tran C.L. Nanoparticles: An Occupational Hygiene Review (2004), Institute of Occupational Medicine for the Health and Safety Executive, Edinburgh http://www.hse.gov.uk/research/rrhtm/rr274.htm
93. Nel A., Xia T., Maedler L., and Li N. Toxic potential of materials at the nanolevel. Science 311 (2006) 622-627
94. Australian Department of Employment and Workplace Relations, Submission to inquiry into workplace exposure to toxic dusts and nanoparticles, Canberra, DEWR (2005) .
95. Garber C. The Potential and the Pitfalls of Nanomedicine (May 7 2007), Nanowerk LLC
96. Nordan M.M., and Holman M.W. A prudent approach to nanotechnology environmental, health and safety risks. Ind. Biotechnol. 1 (2005) 146-149
97. Chaudhry Q., Blackburn J., Floyd P., George C., Nwaogu T., Boxall A., and Aitken R.J. A scoping study to identify gaps in environmental regulation for the products and applications of nanotechnologies (2006), UK Department of Environment, Food and Rural Affairs, London
98. Donaldson K., Aitken R., Tran L., Stone V., Duffin R., Forrest G., and Alexander A. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol. Sci. 92 (2006) 5-22
99. Lacerda L., Bianco A., Prato M., and Kostarelos K. Carbon nanotubes as nanomedicines: from toxicology to pharmacology. Adv. Drug Deliv. Rev. 58 (2006) 1460-1470
100. Potts M., and Short R.V. Using microbicides to fight the spread of HIV. Science 300 (2003) 431
101. Trager R.S. Microbicides: raising new barriers against HIV infection. Science 299 (2003) 39
102. Mullally M.V., and Winn D.R. Patenting Nanotechnology: a Unique Challenge to IP Bar (July 6 2004), N. Y. L. J
103. Maclurcan D.C. AZojono, an AZo Open Access Rewards System Article, Nanotechnology and Developing Countries Part 1 and 2: What Possibilities? (September 30 2005) http://www.azonano.com/oars.asp
104. Harris D., Hermann K., Bawa R., Cleveland J.T., and O'Neill S. Strategies for resolving patent disputes over nanoparticle drug delivery systems. Nanotech. Law Bus. J. 1 (2004) 1-18
105. Nanomarkets, Nano Drug Delivery: The Impact of Nanotechnology in Drug Delivery: Global Developments, Market Analysis and Future Prospects (March 21 2005)
106. Wood S., Jones R., and Geldart A. Nanotechnology: from the science to the social. The Social, Ethical and Economic Aspects of the Debate. A Report for the Economic and Social Research Council (2007)
107. VivaGel Market Update, www.starpharma.com/data/061113%20VivaGel%20Market%20Update.pdf.
108. Forbes/Wolfe Nanotech Report. VivaGel Could Cure Starpharma's Stock vol. 5 (2006) 1-2
109. Milstien J., and Belgharbi L. Regulatory pathways for vaccines for developing countries. Bull. W.H.O. 82 (2004) 128