JBNB  Vol.2 No.5 , December 2011
Bird’s Eye View on the Recent Advances in Drug Delivery Systems
Abstract: Successful treatment of most of the diseases is limited by a lack of safe and effective methods of drug delivery. Drug delivery methods have significant effects on the pharmacological efficacy of a drug. Every drug has an optimum concentration range within which maximum benefit is derived; and concentrations above or below the range can be toxic or provide no therapeutic benefits at all. Therefore, development of an efficient drug delivery system remains an important challenge in medicine, and this can be achieved only through multidisciplinary approaches to the mechanisms of delivery of drugs to targets in tissues. Thus, several drug delivery and drug targeting systems are currently being developed. Targeting is an ability to direct the drug(s) to the desired site. There are two major mechanisms, viz., active and passive for drug targeting. Controlled drug release and subsequent biodegradation are also indispensable for developing successful formulations. Colloidal drug vehicles such as micelles, vesicles, liquid crystal dispersions, and nanomaterials consisting of miniscule nanoparticles of 5 - 200 nm diameter have shown great promise as drug delivery systems. In this context, past decades have witnessed certain major advancements. This review article emphasizes on these advances in the field of drug delivery systems.
Cite this paper: nullPrasad, P. , Pal, P. , Rao, D. , Shrivastav, T. and Ge, R. (2011) Bird’s Eye View on the Recent Advances in Drug Delivery Systems. Journal of Biomaterials and Nanobiotechnology, 2, 544-556. doi: 10.4236/jbnb.2011.225065.

[1]   V. P. Torchilin, “Lipid-Core Micelles for Targeted Drug Delivery,” Current Drug Delivery, Vol. 2, No. 4, 2005, pp. 319-327. doi:10.2174/156720105774370221

[2]   V. P. Torchilin, “Micellar Nanocarriers: Pharmaceutical Perspectives,” Pharmaceutical Research, Vol. 24, No. 1, 2007, pp. 1-16. doi:10.1007/s11095-006-9132-0

[3]   R. R. Sawant and V. P. Torchilin, “Polymeric Micelles: Polyethylene Glycol-Phosphatidylethanolamine (PEG-PE)- Based Micelles as an Example,” Methods in Molecular Biology, Vol. 624, 2010, pp. 131-149. doi:10.1007/978-1-60761-609-2_9

[4]   P. D. Reddy and D. Swarnalatha, “Recent Advances in Novel Drug Delivery Systems,” International Journal of PharmTech Research, Vol. 2, No. 3, 2010, pp. 2025- 2027.

[5]   M. Jahanshahi and Z. Babaei, “Protein Nanoparticle: A Unique System as Drug Delivery Vehicles,” African Journal of Biotechnology, Vol. 7, No. 25, 2008, pp. 4926- 4934.

[6]   F. Scherer, M. Anton, U. Schillinger, J. Henke, C. Bergemann, A. Krager, B. Gonsbacher and C. Plank, “Magnetofection: Enhancing and targeting Gene Delivery by Magnetic Force in Vitro and in Vivo,” Gene Therapy, Vol. 9, No. 2, 2002, pp. 102-109. doi:10.1038/

[7]   J. Dobson, “Gene Therapy Progress and Prospects: Magnetic Nanoparticle-Based Gene Delivery,” Gene Therapy, Vol. 13, 2006, pp. 283-287. doi:10.1038/

[8]   M. Mahmoudi, A. Simchi and M. Imani, “Recent Advances in Surface Engineering of Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications,” Journal of Iranian Chemical Society, Vol. 7, 2010, pp. S1-S27.

[9]   K.-O. Kim, B.-S. Kim and I.-S. Kim, “Self-Ssembled Core-Shell Poly(EthyleneGlycol)-POSS Nanocarriers for Drug Delivery,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, No. 3, 2011, pp. 201-206. doi:10.4236/jbnb.2011.23025

[10]   L. W. Thomas, D. T. Simpson, T. N. Val, Z. Yu, K. T. Lim, E. J. Park, R. O. Williams III and K. P. Johnston, “Encapsulation of Protein Nanoparticles into Uniform- Sized Microspheres Formed in a Spinning Oil Film,” AAPS PharmSciTech, Vol. 6, No. 4, 2005, pp. E605- E617.

[11]   A. Chonn and P. R. Cullis, “Recent Advances in Liposomal Drug-Delivery Systems,” Current Opinion in Biotechnology, Vol. 6, No. 6, 1995, pp. 698-708. doi:10.1016/0958-1669(95)80115-4

[12]   J. Kunisawa, T. Masuda, K. Katayama, T. Yoshikawa, Y. Tsutsumi, M. Akashi, T. Mayumi and S. Nakagawa, “Fusogenic Liposome Delivers Encapsulated Nanoparticles for Cytosolic Controlled Gene Release,” Journal of Controlled Release, Vol. 105, No. 3, 2005, pp. 344-353. doi:10.1016/j.jconrel.2005.03.020

[13]   D. J. Bharali, M. Khalil, M Gurbuz, T. M. Simone and S. A. Mousa, “Nanoparticles and Cancer Therapy: A Concise Review with Emphasis on Dendrimers,” International Journal of Nanomedicine, Vol. 4, 2009, pp. 1-7.

[14]   J. E. Adrian, H. W. Morselt, R. Süss, S. Barnert, J. W. Kok, S. A. Asgeirsdóttir, M. H. Ruiters, G. Molema and J. A. Kamps, “Targeted SAINT-O-Somes for Improved Intracellular Delivery of siRNA and Cytotoxic Drugs into Endothelial Cells,” Journal of Controlled Release, Vol. 144, No. 3, 2010, pp. 341-349. doi:10.1016/j.jconrel.2010.03.003

[15]   A. Csiszar, N. Hersch, S. Dieluweit, R. Biehl, R. Merkel and B. Hoffmann, “Novel Fusogenic Liposomes for Fluorescent Cell Labeling and Membrane Modification,” Bioconjugate Chemistry, Vol. 21, No. 3, 2010, pp. 537- 543. doi:10.1021/bc900470y

[16]   M. Ferrari, “Cancer Nanotechnologies: Opportunities and Challenges,” Nature Reviews: Cancer, Vol. 5, No. 3, 2005, pp. 161-171. doi:10.1038/nrc1566

[17]   H. S. Sharma, D. F. Muresanu, A. Sharma, R. Patnaik and J. V. Lafuente, “Chapter 9—Nanoparticles Influence Pathophysiology of Spinal Cord Injury and Repair,” Progress in Brain Research, Vol. 180, 2009, pp. 154-180. doi:10.1016/S0079-6123(08)80009-X

[18]   H. S. Sharma, S. F. Ali, Z. R. Tian, R. Patnaik, S. Patnaik, A. Sharma, A. Boman, P. Lek, E. Seifert and T. Lundstedt, “Nanowired-Drug Delivery Enhances Neuroprotective Efficacy of Compounds and Reduces Spinal Cord Edema Formation and Improves Functional Outcome Following Spinal Cord Injury in the Rat,” Acta Neurochir Supplement, Vol. 106, 2010, pp. 343-350. doi:10.1007/978-3-211-98811-4_63

[19]   K. E. Fischer, B. J. Alemán, S. L. Tao, R. Hugh Daniels, E. M. Li, M. D. Bünger, G. Nagaraj, P. Singh, A. Zettl and T. A. Desai, “Biomimetic Nanowire Coatings for Next Generation Adhesive Drug Delivery Systems,” Nanotechnology Letters, Vol. 9, No. 2, 2009, pp. 716- 720.

[20]   H. Liou, H. Lin, Y. Hwu, W. Chen, W. Liou, L. Lai, W. Lin and W. Chiou, “Synthesis and Characterization of Novel Hybrid Poly(methyl methacrylate)/Iron Nanowires for Potential Hyperthemia Therapy,” Journal of Biomaterials and Nanobiotechnology, Vol. 1, 2010, pp. 50-60. doi:10.4236/jbnb.2010.11007

[21]   G. A. Hughes, “Nanostructure-Mediated Drug Delivery,” Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 1, No. 1, 2005, pp. 22-30. doi:10.1016/j.nano.2004.11.009

[22]   M. Bikram, A. M. Gobin, R. E. Whitmire and J. L. West, “Temperature-Sensitive Hydrogels with SiO2-Au Nano-shells for Controlled Drug Delivery,” Journal of Controlled Release, Vol. 123, No. 3, 2007, pp. 219-227. doi:10.1016/j.jconrel.2007.08.013

[23]   I. Bob, “Nanoparticle Drug Delivery Systems,” Innovations in Pharmaceutical Technology, Vol. 24, 2007, pp. 58-62.

[24]   M. M. De Villiers and Y. M. Lvov, “Nanoshells for Drug Delivery,” Nanotechnologies for the Life Sciences, Published Online 15 September 2007.

[25]   K. Noh, K. S. Brammer, C. Choi, S. Kim, C. J. Frandsen and S. Jin, “A New Nano-Platform for Drug Release via Nanotubular Aluminum Oxide,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, 2011, pp. 226-233. doi:10.4236/jbnb.2011.23028

[26]   R. J. Chen and D. Hongjie, “Noncovalent Functionalization of Carbon Nanotubes for Highly Specific Electronic Biosensors,” Proceedings of National Academy of Sciences, USA, Vol. 100, No. 9, 2003, pp. 4984-4989.

[27]   A. Woolley, et al., “Direct Haplotyping of Kilobase-Size DNA Using Carbon Nanotube Probes,” Nature Biotechnology, Vol. 18, 2000, pp. 760-764. doi:10.1038/77760

[28]   A. L. Yarin, “Nanofibers, Nanofluidics, Nanoparticles and Nanobots for Drug and Protein Delivery Systems,” Scientia Pharmaceutica, Vol. 78, 2010, p. 542. doi:10.3797/scipharm.cespt.8.L02

[29]   “Nanoneedles Make Injections Painless,”

[30]   T. Vieru, “Nanoneedles May Change the Face of Medicine,” Accessed on 29 April 2009.

[31]   A. Lewcock, “Carbon Nanoneedles for Drug Delivery,” Accessed on 8 February 2007.

[32]   H. Chen, J. Han, J. Li and M. Meyyappan, “Microelectronic DNA Assay for the Detection of BRCA1 Gene Mutations,” Biomedical Microdevices, Vol. 6, No. 1, 2004, pp. 55-60. doi:10.1023/B:BMMD.0000013366.85609.dd

[33]   S. Sengupta and R. Sasisekharan, “Exploiting Nanotechnology to Target Cancer,” British Journal of Cancer, Vol. 96, No. 9, 2007, pp. 1315-1319. doi:10.1038/sj.bjc.6603707

[34]   P. A. Shashishekar, C. Jin, L. A. Curtiss, Nancy A. Monteiro-Riviere and R. J. Narayan, “Nanoporous Membranes for Medical and Biological Applications,” WIREs Nano- medicine and Nanobiotechnology, Vol. 1, No. 5, 2009, pp. 568-581. doi:10.1002/wnan.50

[35]   T. Lebold, C. Jung, J. Michaelis and C. Bra¨uchle, “Nanostructured Silica Materials as Drug-Delivery Systems for Doxorubicin: Single Molecule and Cellular Studies,” Nano Letters, Vol. 9, No. 8, 2009, pp. 2877- 2883. doi:10.1021/nl9011112

[36]   N. Darshana, K. S. Rathore, M. Bharkatiya, S. S. Sisodia and R. K. Nema, “Bucky Balls: A Novel Drug Delivery System,” Journal of Chemical and Pharmaceutical Research, Vol. 2, No. 2, 2010, pp. 240-248.

[37]   W. C. W. Chan, “Bio-Applications of Nanoparticles,” Landes Bioscience, Austin, USA, 2007.

[38]   C. A. Mirkin, R. L. Letsinger, R. C. Mucic and J. J. Storhoff, “A DNA Based Method for Rationally Assembling Nanoparticles into Macroscopic Materials,” Nature, Vol. 382, No. 6592, 1996, pp. 607-609. doi:10.1038/382607a0

[39]   G. F. Paciotti, M. Lonnie, D. Weinreich, D. Goia, N. Pavel, R. E. McLaughlin and T. Lawrence, “Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery,” Drug Delivery, Vol. 11, No. 3, 2004, pp. 169-183. doi:10.1080/10717540490433895

[40]   X. Wu and M. P. Bruchez, “Immunofluorescent Labeling of Cancer Marker Her2 and Other Cellular Targets with Semiconductor Quantum Dots,” Nature Biotechnology, Vol. 21, 2003, pp. 41-46. doi:10.1038/nbt764

[41]   J. K. Jaiswal and S. M. Simon, “Long-Term Multiple Color Imaging of Live Cells Using Quantum Dot Bioconjugates,” Nature Biotechnology, Vol. 21, No. 1, 2003, pp. 47-51. doi:10.1038/nbt767

[42]   X. H. Gao and S. M. Nie, “Molecular Profiling of Single Cells and Tissue Specimens with Quantum Dots,” Trends in Biotechnology, Vol. 21, No. 9, 2003, pp. 371-373. doi:10.1016/S0167-7799(03)00209-9

[43]   T. M. Jovin, “Quantum Dots Finally Come of Age,” Nature Biotechnology, Vol. 21, 2003, pp. 32-33. doi:10.1038/nbt0103-32

[44]   S. K. Vashist, R. Tewari, R. P. Bajpai, L. M. Bharadwaj and R. Roberto, “Review of Quantum Dot Technologies for Cancer Detection and Treatment,” Journal of Nano- technology, Online, 13 September 2006.

[45]   L. Qi and X. Gao, “Emerging Application of Quantum Dots for Drug Delivery and Therapy,” Expert Opinion in Drug Delivery, Vol. 5, No. 3, 2008, pp. 263-267. doi:10.1517/17425247.5.3.263

[46]   A. Bianco, K. Kostarelos and M. Prato, “Applications of Carbon Nanotubes in Drug Delivery,” Current Opinion in Chemical Biology, Vol. 9, No. 6, 2005, pp. 674-679. doi:10.1016/j.cbpa.2005.10.005

[47]   L. Lacerda, A. Bianco, M. Prato and K. Kostarelos, “Carbon Nanotubes as Nanomedicines: From Toxicology to Pharmacology,” Advanced Drug Delivery Reviews, Vol. 58, No. 14, 2006, pp. 1460-1470. doi:10.1016/j.addr.2006.09.015

[48]   C. Klumpp, K. Kostarelos, M. Prato and A. Bianco, “Functionalized Carbon Nanotubes as Emerging Nanovectors for the Delivery of Therapeutics,” Biochimica et Biophysica Acta—Biomembranes, Vol. 1758, No. 3, 2006, pp. 404-412.

[49]   N. W. Kam, M. O’Connell, J. A. Wisdom and H. Dai, “Carbon Nanotubes as Multifunctional Biological Transporters and Near-Infrared Agents for Selective Cancer Cell Destruction,” Proceedings of National Academy of Sciences, USA, Vol. 102, No. 33, 2005, pp. 11600-11605. doi:10.1073/pnas.0502680102

[50]   M. Lou and E. Jonckheere, “Magnetically Levitated Nano-robots: An Application to Visualization of Nerve Cells Injuries,” Studies on Health Technology and Information, Vol. 125, 2007, pp. 310-312.

[51]   Nanotech Web, Accessed on 15 January 2009.

[52]   A. Rastogi, T. Bose, M. D. Feldman, D. Patel and S. Stavchansky, “Characterization of Nanoporous Surfaces as Templates for Drug Delivery Devices,” Journal of American Association of Pharmaceutical Scientists, Vol. 11, 2009, pp. 758-761.

[53]   Y. Cheng, J. Wang, T. Rao, X. He and T. Xu, “Pharmaceutical Applications of Dendrimers: Promising Nanocarriers for Drug Delivery,” Frontiers in Biosciences, Vol. 13, 2008, pp. 1447-1471. doi:10.2741/2774

[54]   A. Samad, M.I. Alam and K. Saxena, “Dendrimers: A Class of Polymers in the Nanotechnology for the Delivery of Active Pharmaceuticals,” Current Pharmaceuticals Design, Vol. 15, No. 25, 2009, pp. 2958-2969. doi:10.2174/138161209789058200

[55]   J. Kopecek, “Smart and Genetically Engineered Biomaterials and Drug Delivery Systems,” European Journal of Pharmaceutical Sciences, Vol. 20, No. 1, 2003, pp. 1-16. doi:10.1016/S0928-0987(03)00164-7

[56]   S. A. Agnihotri, N. N. Mallikarjuna and T. M. Aminabhavi, “Recent Advances on Chitosan-Based Micro- and Nanoparticles in Drug Delivery,” Journal of Controlled Release, Vol. 100, No. 1, 2004, pp. 5-28. doi:10.1016/j.jconrel.2004.08.010

[57]   P. Tangri and N. V. Satheesh Madhav, “Recent Advances in Oral Mucoadhesive Drug Delivery Systems: A Review,” (Online, Publication Ref No.: IJPRD/ 2011/PUB/ARTI/VOV-3/ISSUE-2/APRIL/018; ISSN 0974-9446.

[58]   M. Sadeghi, “Pectin-Based Biodegradable Hydrogels with Potential Biomedical Applications as Drug Delivery Systems,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, 2011, pp. 36-40. doi:10.4236/jbnb.2011.21005

[59]   N. Saha, A. Saarai, N. Roy, T. Kitano and P. Saha, “Polymeric Biomaterial Based Hydrogels for Biomedical Applications,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, 2011, pp. 85-90. doi:10.4236/jbnb.2011.21011

[60]   A. D. Dinsmore, M. F. Hsu, M. G. Nikolaides, M. Marquez, A. R. Bausch and D. A. Weitz, “Colloidosomes: Selectively Permeable Capsules Composed of Colloidal Particles,” Science, Vol. 298, No. 5595, 2002, pp. 1006- 1009. doi:10.1126/science.1074868

[61]   R. T. Rosenberg and N. Dan, “Self-Assembly of Colloidosome Shells on Drug-Containing Hydrogels,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, 2011, pp. 1-7. doi:10.4236/jbnb.2011.21001

[62]   “Oral Thin Films,” In: Orally Disintegrating Tablet and Film Technologies, 5th Edition, Technology Catalysts International, Falls Church, VA, 2008.

[63]   S. K. Singh, D. N. Mishra, R. Jassal and P. Soni, “Fast Disintegrating Combination Tablets of Omeprazole, and Domperidone,” Asian Journal of Pharmaceutical and Clinical Research, Vol. 2, No. 3, 2009, pp. 74-82.

[64]   D. Bhowmik, B. Chiranjib, Krishnakanth, Pankaj and R. M. Chandira, “Fast Dissolving Tablet: An Overview,” Journal of Chemical and Pharmaceutical Research, Vol. 1, No. 1, 2009, pp. 163-177.

[65]   A. Baichwall, “Culturing Innovation and Enhancing Medications Using Oral Drug Delivery,” Drug Development and Delivery, Vol. 2, 2002.

[66]   I. I. Slowing, B. G. Trewyn and V. S.-Y. Lin, “Mesoporous Silica Nanoparticles for Intracellular Delivery of Membrane-Impermeable Proteins,” Journal of American Chemical Society, Vol. 129, No. 28, 2007, pp. 8845-8849. doi:10.1021/ja0719780

[67]   F. Balas, M. Manzano, M. Colilla, et al., “L-Trp Absorption into Silica Mesoporous Materials to Promote Bone Formation,” Acta Biomaterialia, Vol. 4, No. 3, 2008, pp. 514-522. doi:10.1016/j.actbio.2007.11.009

[68]   M. Colilla, M. Manzano and M. Vallet-Regi, “Recent Advances in Ceramic Implants as Drug Delivery Systems for Biomedical Applications,” International Journal of Nanomedicine, Vol. 3, No. 4, 2008, pp. 403-414.

[69]   M. Vallet-Regi, M. Colilla and I. Izquierdo-Barba, “Bioactive Mesoporous Silica as Controlled Delivery Systems: Application in Bone Tissue Regeneration,” Journal of Biomedical Nanotechnology, Vol. 4, No. 3, 2008, pp. 1-15.

[70]   S. R. Milligan and P. E. Cohen, “Silastic Implants for Delivering Physiological Concentrations of Progesterone to Mice,” Reproduction Fertility and Development, Vol. 6, No. 2, 1994, pp. 235-239. doi:10.1071/RD9940235

[71]   R. Sitruk-Ware, M. Small, N. Kumar, Y. Y. Tsong, K. Sundaram and T. Jackanicz, “Nestorone: Clinical Applications for Contraception and HRT,” Steroids, Vol. 68, No. 10, 2003, pp. 907-913. doi:10.1016/S0039-128X(03)00140-5

[72]   W. E. Lynch, G. P. Sartiano and A. Ghaffar, “Erythrocytes as Carriers of Chemotherapeutic Agents for Targeting the Reticuloendothelial System,” American Journal of Hematology, Vol. 9, No. 3, 1980, pp. 249-259. doi:10.1002/ajh.2830090303

[73]   P. D. Patel, N. Dand, R. S. Hirlekar and V. J. Kadam, “Drug Loaded Erythrocytes: As Novel Drug Delivery System,” Current Pharmaceutical Design, Vol. 14, No. 1, 2008, pp. 63-70. doi:10.2174/138161208783330772

[74]   A. Pathak, V. Jain, A. K. Nagariya, R. Singh, S. Nayak, P. Bansal, V. Gupta, S. Kumar and H. Singh, “Recent Advances in Self Emulsifying Drug Delivery System—A Review,” Drug Invention Today, Vol. 2, No. 2, 2010, pp. 123-129.

[75]   A. Spernath and A. Aserin, “Microemulsions as Carriers for Drugs and Nutraceuticals,” Advances in Colloid Interface Sciences, Vol. 128-130, 2006, pp. 47-64. doi:10.1016/j.cis.2006.11.016

[76]   T. Manabe, H. Okino, R. Maeyama, K. Mizumoto, E. Nagai, et al., “Novel Strategic Therapeutic Approaches for Prevention of Local Recurrence of Pancreatic Cancer after Resection: Trans-Tissue, Sustained Local Drug-Delivery Systems,” Journal of Controlled Release, Vol. 100, No. 3, 2004, pp. 317-330. doi:10.1016/j.jconrel.2004.09.007

[77]   C. B. Packhaeuser, J. Schnieders, C. G. Oster and T. Kissel, “In Situ Forming Parenteral Drug Delivery Systems: An Overview,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 58, No. 2, 2004, pp. 445-455. doi:10.1016/j.ejpb.2004.03.003

[78]   M. Cobleigh, V. K. Langmuir, G. W. Sledge, K. D. Miller, L. Haney, et al., “A Phase I/II Dose-Escalation Trial of Bevacizumab in Previously Treated Metastatic Breast Cancer,” Seminars in Oncology, Vol. 30, No. 5, 2003, pp. 117-124. doi:10.1053/j.seminoncol.2003.08.013

[79]   V. P. Torchilin, “Multifunctional Nanocarriers,” Advances in Drug Delivery Reviews, Vol. 58, No. 14, 2006, pp. 1532-1555. doi:10.1016/j.addr.2006.09.009

[80]   G. P. Andrews, et al., “Mucoadhesive Polymeric Platforms for Controlled Drug Delivery,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 71, No. 3, 2009, pp. 505-518. doi:10.1016/j.ejpb.2008.09.028

[81]   I. S. Fraser, E. Weisberg, N. Kumar, A. J. Humberstone, L. McCrossin, et al., “An Initial Pharmacokinetic Study with a Metered Dose Transdermal System for Delivery of the Progestogen Nestorone as a Possible Future Contraceptive,” Contraception, Vol. 76, No. 6, 2007, pp. 432- 438. doi:10.1016/j.contraception.2007.08.006

[82]   A. Bakshi, A. Bajaj, G. Malhotra, M. Madan and N. Amrutiya, “A Novel Metered Dose Transdermal Spray Formulation for Oxybutynin,” Indian Journal of Pharmaceutical Sciences, Vol. 70, No. 6, 2008, pp. 733-739. doi:10.4103/0250-474X.49094

[83]   S. Shaikh, S. Nazim, T. Khan, A. Shaikh, A. Zameeruddin and A. Quazi, “Recent Advances in Pulmonary Drug Delivery System: A Review,” International Journal of Applied Pharmaceutics, Vol. 2, 2010, pp. 27-31.

[84]   Lewis Jr., et al., “Acoustic Targeted Drug Delivery in Neurological Tissue,” 2007,

[85]   Lewis Jr., et al., “Acoustic Chemotherapy and Brain Cancer,” 2007.

[86]   N. Jovanovic, A. Bouchard, G. W. Hofland, G. J. Witkamp, D. J. Crommelin and W. Jiskoot, “Stabilization of Proteins in Dry Powder Formulations Using Supercritical Fluid Technology,” Pharmaceutical Research, Vol. 21, No. 11, 2004, pp. 1955-1969. doi:10.1023/B:PHAM.0000048185.09483.e7

[87]   A. R. Duarte, M. S. Costa, A. L. Simplício, M. M. Cardoso and C. M. Duarte, “Preparation of Controlled Release Microspheres Using Supercritical Fluid Technology for Delivery of Anti-Inflammatory Drugs,” International Journal of Pharmacology, Vol. 308, 2006, pp. 168-174. doi:10.1016/j.ijpharm.2005.11.012

[88]   K. Byrappa, S. Ohara and T. Adschiri, “Nanoparticles Synthesis Using Supercritical Fluid Technology—Towards Biomedical Applications,” Advanced Drug Delivery Reviews, Vol. 60, No. 3, 2008, pp. 299-327. doi:10.1016/j.addr.2007.09.001

[89]   T. Yasuji, H. Takeuchi and Y. Kawashima, “Particle Design of Poorly Water-Soluble Drug Substances Using Supercritical Fluid Technologies,” Advanced Drug Delivery Reviews, Vol. 60, No. 3, 2008, pp. 388-398. doi:10.1016/j.addr.2007.03.025

[90]   S. P. Cape, J. A. Villa, E. T. S. Huang, T. Yang, J. F. Carpenter and R. E. Sievers, “Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids,” Pharmaceutical Research, Vol. 25, No. 9, 2008, pp. 1967-1990. doi:10.1007/s11095-008-9575-6

[91]   BCC Research LLC, 49 Walnut Park, Building 2, Wellesley, MA 02481, USA.

[92]   B. C. Blount, M. J. Silva, S. P. Caudill, L. L. Needham, J. L. Prikle, E. J. Sampson, G. W. Lucier, R. J. Jackson and J. W. Brock, “Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population,” Environmental Health Perspectives, Vol. 108, No. 10, 2000, pp. 979-982. doi:10.1289/ehp.00108979

[93]   NTP-CERHR, “Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP),” NTP CERHR MON, 2003, Apr(4), i-III90.

[94]   H. M. Koch, H. Drexler and J. Angerer, “Internal Exposure of Nursery-School Children and Their Parents and Teachers to Di-(2-ethyl hexyl) Phthalate (DEHP),” International Journal of Hygiene and Environmental Health, Vol. 207, No. 1, 2004, pp. 15-22. doi:10.1078/1438-4639-00270

[95]   S. H. Swan, K. M. Main, F. Liu, S. L. Stewart, R. L. Kruse, et al., “Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure,” Environmental Health Perspectives, Vol. 113, 2005, pp. 1056-1061. doi:10.1289/ehp.8100