Pharmaceutical Research

, Volume 28, Issue 6, pp 1241–1258 | Cite as

Controlled Delivery Systems: From Pharmaceuticals to Cells and Genes

Expert Review

ABSTRACT

During the last few decades, a fair amount of scientific investigation has focused on developing novel and efficient drug delivery systems. According to different clinical needs, specific biopharmaceutical carriers have been proposed. Micro- and nanoparticulated systems, membranes and films, gels and even microelectronic chips have been successfully applied in order to deliver biopharmaceuticals via different anatomical routes. The ultimate goal is to deliver the potential drugs to target tissues, where regeneration or therapies (chemotherapy, antibiotics, and analgesics) are needed. Thereby, the bioactive molecule should be protected against environmental degradation. Delivery should be achieved in a dose- and time-correct manner. Drug delivery systems (DDS) have been conceived to provide improvements in drug administration such as ability to enhance the stability, absorption and therapeutic concentration of the molecules in combination with a long-term and controlled release of the drug. Moreover, the adverse effects related with some drugs can be reduced, and patient compliance could be improved. Recent advances in biotechnology, pharmaceutical sciences, molecular biology, polymer chemistry and nanotechnology are now opening up exciting possibilities in the field of DDS. However, it is also recognized that there are several key obstacles to overcome in bringing such approaches into routine clinical use. This review describes the present state-of-the-art DDS, with examples of current clinical applications, and the promises and challenges for the future in this innovative field.

KEY WORDS

cell encapsulation DDS routes of administration gene therapy growth factors nanotechnology regenerative medicine 

ABBREVIATIONS

BMP-2

bone morphogenetic protein 2

BSA

bovine serum albumin

cDNA

complementary DNA

DDS

drug delivery systems

ECM

extracellular matrix

HEMA-MMA

Hydroxyethylmethacrylate- Methyl methacrylate

IGF-I

insulin-like growth factor 1

PC12

cell line derived from a pheochromocytoma of the rat adrenal medulla

PDGF

platelet-derived growth factor

PLA-PEG

Polylactic acid-polyethylene glycol

PLGA-m-PEG

Poly(lactic-co-glycolic acid)-methoxy-polyethylene glycol

VEGF

vascular endothelial growth factor

Notes

ACKNOWLEDGMENTS

This work was supported through the European Union funded projects Marie Curie Host Fellowships for Early Stage Research Training (EST) “Alea Jacta EST” (MEST-CT-2004-008104), which provided E. R. Balmayor with a PhD fellowship, and the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-500283).

REFERENCES

  1. 1.
    Berkowitz AC, Goddard DM. Novel drug delivery systems: future directions. J Neurosci Nurs. 2009;41:115–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Orive G, Hernández RM, Gascón AR, Domínguez-Gil A, Pedraz JL. Drug delivery in biotechnology: present and future. Curr Opin Biotechnol. 2003;14:659–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Paolino D, Fresta M, Sinha P, Ferrari M. Drug Delivery Systems. In: Webster JG, editor. Encyclopedia of medical devices and instrumentation. New York: Wiley; 2006. p. 437–95.Google Scholar
  4. 4.
    Balmayor ER, Tuzlakoglu K, Azevedo HS, Reis RL. Preparation and characterization of starch-poly-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications. Acta Biomater. 2009;5:1035–45.PubMedCrossRefGoogle Scholar
  5. 5.
    Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev. 2007;59:207–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Wenk E, Wandrey AJ, Merkle HP, Meinel L. Silk fibroin spheres as a platform for controlled drug delivery. J Control Release. 2008;132:26–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Ranade W. Drug delivery systems. Implants in drug delivery. J Clin Pharmacol. 1990;30:871–89.PubMedGoogle Scholar
  8. 8.
    Nitsch MJ, Banakar UV. Implantable drug delivery. J Biomater Appl. 1994;8:247–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Pioletti DP, Gauthier O, Stadelmann VA, Bujoli B, Guicheux J, Zambelli PY, et al. Orthopedic implant used as drug delivery system: clinical situation and state of the research. Curr Drug Deliv. 2008;5:59–63.PubMedCrossRefGoogle Scholar
  10. 10.
    Parvizi J, Antoci V, Hickok NJ, Shapiro IM. Selfprotective smart orthopedic implants. Expert Rev Med Devices. 2007;4:55–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Langer R, Peppas NA. Advances in biomaterials, drug delivery, and bionanotechnology. AIChE J. 2003;49:2990–3006.CrossRefGoogle Scholar
  12. 12.
    Rosen H, Abribat T. The rise and rise of drug delivery. Nat Rev Drug Discov. 2005;4:381–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Jain KK. Strategies and technologies for drug delivery systems. Trends Pharmacol Sci. 1998;19:155–7.CrossRefGoogle Scholar
  14. 14.
    Orive G, Gascon AR, Hernandez RM, Dominguez-Gil A, Pedraz JL. Techniques: new approaches to the delivery of biopharmaceuticals. Trends Pharmacol Sci. 2004;25:382–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Arora A, Prausnitz MR, Mitragotri S. Micro-scale devices for transdermal drug delivery. Int J Pharm. 2008;364:227–36.PubMedCrossRefGoogle Scholar
  16. 16.
    Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26:1261–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3:115–24.PubMedCrossRefGoogle Scholar
  18. 18.
    Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv. 2004;4:308–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Vilivalam VD, Illum L, Iqbal K. Starch capsules: an alternative system for oral drug delivery. Pharm Sci Technolo Today. 2000;3:64–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Majuru S. Advances in the oral delivery of heparin from solid dosage forms using emisphere’s eligen® oral drug delivery technology. Drug Deliv Technol. 2004;4:9–14.Google Scholar
  21. 21.
    Hosny EA, Al-Shora HI, Elmazar MM. Oral delivery of insulin from enteric-coated capsules containing sodium salicylate: effect on relative hypoglycemia of diabetic beagle dogs. Int J Pharm. 2002;237:71–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenblatt JS, Berg RA. Collagen-based injectable drug delivery system and its use. 1998. US Patent Specification 5807581. United StateGoogle Scholar
  23. 23.
    Bernstein G. Delivery of insulin to the buccal mucosa utilizing the RapidMist™ system. Expert Opin Drug Deliv. 2008;5:1047–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Rogueda P. Novel hydrofluoroalkane suspension formulations for respiratory drug delivery. Expert Opin Drug Deliv. 2005;2:625–38.PubMedCrossRefGoogle Scholar
  25. 25.
    Yang JZ, Young AL, Chiang P-C, Thurston A, Pretzer DK. Fluticasone and budesonide nanosuspensions for pulmonary delivery: Preparation, characterization, and pharmacokinetic studies. J Pharm Sci. 2008;97:4869–78.PubMedCrossRefGoogle Scholar
  26. 26.
    Engstrom JD, Tam JM, Miller MA, Williams RO, Johnston KP. Templated open flocs of nanorods for enhanced pulmonary delivery with pressurized metered dose inhalers. Pharm Res. 2008;26:101–17.PubMedCrossRefGoogle Scholar
  27. 27.
    Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56:603–18.PubMedCrossRefGoogle Scholar
  28. 28.
    Smith EW, Maibach HI. In: Smith EW, Maibach HI, editors. Percutaneous penetration enhancers. Boca Raton: CRC Press. Taylor & Francis Group; 2006. p. 4–14.Google Scholar
  29. 29.
    Vaddi HK, Ho PC, Chan SY. Terpenes in propylene glycol as skin-penetration enhancers: Permeation and partition of haloperidol, fourier transform infrared spectroscopy, and differential scanning calorimetry. J Pharm Sci. 2002;91:1639–51.PubMedCrossRefGoogle Scholar
  30. 30.
    Tang H, Blankschtein D, Langer R. Effects of low-frequency ultrasound on the transdermal permeation of mannitol: Comparative studies with in vivo and in vitro skin. J Pharm Sci. 2002;91:1776–94.PubMedCrossRefGoogle Scholar
  31. 31.
    McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles for gene and drug delivery. Annu Rev Biomed Eng. 2000;2:289–313.PubMedCrossRefGoogle Scholar
  32. 32.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci USA. 2003;100:13755–60.PubMedCrossRefGoogle Scholar
  33. 33.
    Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87:922–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Lin W, Cormier M, Samiee A, Griffin A, Johnson B, Teng CL, et al. Transdermal delivery of antisense oligonucleotides with microprojection patch (Macroflux) technology. Pharm Res. 2001;18:1789–93.PubMedCrossRefGoogle Scholar
  35. 35.
    Martanto W, Davis SP, Holiday NR, Wang J, Gill HS, Prausnitz MR. Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004;21:947–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Cormier M, Daddona PE. Macroflux technology for transdermal delivery of therapeutic proteins and vaccines. In: Rathbone MJ, Hadgraft J, Roberts MS, editors. Modified-release drug delivery technology. New York: Marcel Dekker, Inc.; 2003. p. 589–98.Google Scholar
  37. 37.
    Kaushik S, Hord AH, Denson DD, McAllister DV, Smitra S, Allen MG, et al. Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001;92:502–4.PubMedCrossRefGoogle Scholar
  38. 38.
    Laurent PE, Bonnet S, Alchas P, Regolini P, Mikszta JA, Pettis R, et al. Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system. Vaccine. 2007;25:8833–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Wermeling DP, Banks SL, Hudson DA, Gill HS, Gupta J, Prausnitz MR, et al. Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci USA. 2008;105:2058–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Dean CH, Alarcon JB, Waterston AM, Draper K, Early R, Guirakhoo F, et al. Cutaneous delivery of a live, attenuated chimeric flavivirus vaccine against Japanese encephalitis (ChimeriVax)-JE) in non-human primates. Hum Vaccin. 2005;1:106–11.PubMedCrossRefGoogle Scholar
  41. 41.
    Mutwiri G, Bowersock TL, Babiuk LA. Microparticles for oral delivery of vaccines. Expert Opin Drug Deliv. 2005;2:791–806.PubMedCrossRefGoogle Scholar
  42. 42.
    Lavelle EC, O’Hagan DT. Delivery systems and adjuvants for oral vaccines. Expert Opin Drug Deliv. 2006;3:747–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Maroni A, Zema L, Cerea M, Sangalli ME. Oral pulsatile drug delivery systems. Expert Opin Drug Deliv. 2005;2:855–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Rhodes CT, Porter SC. Coatings for controlled release drug delivery systems. Drug Dev Ind Pharm. 1998;24:1139–54.PubMedCrossRefGoogle Scholar
  45. 45.
    Lambkin I, Pinilla C. Targeting approaches to oral drug delivery. Expert Opin Biol Ther. 2002;2:67–73.PubMedCrossRefGoogle Scholar
  46. 46.
    Peppas NA, Robinson JR. Bioadhesives for optimization of drug delivery. J Drug Target. 1995;3:183–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Simone EA, Dziubla TD, Muzykantov VR. Polymeric carriers: role of geometry in drug delivery. Expert Opin Drug Deliv. 2008;5:1283–300.PubMedCrossRefGoogle Scholar
  48. 48.
    Anderson RU, Mobley D, Blank B, Saltzstein D, Susset J, Brown JS. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. OROS Oxybutynin Study Group. J Urol. 1999;161:1809–12.PubMedCrossRefGoogle Scholar
  49. 49.
    Versi E, Appell R, Mobley D, Patton W, Saltzstein D. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group. Obstet Gynecol. 2000;95:718–21.PubMedCrossRefGoogle Scholar
  50. 50.
    Swanson J, Gupta S, Lam A, Shoulson I, Lerner M, Modi N, et al. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies. Arch Gen Psychiatry. 2003;60:204–11.PubMedCrossRefGoogle Scholar
  51. 51.
    Conte U, Maggi L, Colombo P, Lamanna A. Multilayered hydrophilic matrices as constant release devices (Geomatrix(Tm) Systems). J Control Release. 1993;26:39–47.CrossRefGoogle Scholar
  52. 52.
    Conte U, Maggi L. Modulation of the dissolution profiles from Geomatrix multi-layer matrix tablets containing drugs of different solubility. Biomaterials. 1996;17:889–96.PubMedCrossRefGoogle Scholar
  53. 53.
    Ozsoy Y, Gungor S, Cevher E. Nasal delivery of high molecular weight drugs. Molecules. 2009;14:3754–79.PubMedCrossRefGoogle Scholar
  54. 54.
    Jain SK, Chourasia MK, Jain AK, Jain RK, Shrivastava AK. Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery. Drug Deliv. 2004;11:113–22.PubMedCrossRefGoogle Scholar
  55. 55.
    Gungor S, Okyar A, Erturk-Toker S, Baktir G, Ozsoy Y. Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes. Drug Dev Ind Pharm. 2010;36:806–13.PubMedCrossRefGoogle Scholar
  56. 56.
    Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85:1017–25.PubMedCrossRefGoogle Scholar
  57. 57.
    Merkus FWHM, Verhoef JC, Marttin E, Romeijn SG, van der Kuy PHM, Hermens WAJJ, et al. Cyclodextrins in nasal drug delivery. Adv Drug Deliv Rev. 1999;36:41–57.PubMedCrossRefGoogle Scholar
  58. 58.
    Hayes RP, Muchmore D, Schmitke J. Effect of inhaled insulin on patient-reported outcomes and treatment preference in patients with type 1 diabetes. Curr Med Res Opin. 2007;23:435–42.PubMedCrossRefGoogle Scholar
  59. 59.
    Otulana B, Okikawa J, Linn L, Morishige R, Thipphawong J. Safety and pharmacokinetics of inhaled morphine delivered using the AERx system in patients with moderate-to-severe asthma. Int J Clin Pharmacol Ther Toxicol. 2004;42:456–62.Google Scholar
  60. 60.
    Davison S, Thipphawong J, Blanchard J, Liu K, Morishige R, Gonda I, et al. Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women. J Clin Pharmacol. 2005;45:177–84.PubMedCrossRefGoogle Scholar
  61. 61.
    Jiang RG, Pan WS, Wang CL, Liu H. Use of recrystallized lactose as carrier for inhalation powder of interferon a2b. Pharmazie. 2005;60:632–3.PubMedGoogle Scholar
  62. 62.
    Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymers. 2008;49:1993–2007.CrossRefGoogle Scholar
  63. 63.
    Malafaya PB, Silva GA, Baran ET, Reis RL. Drug delivery therapies II.: strategies for delivering bone regenerating factors. Curr Opin Solid State Mater Sci. 2002;6:297–312.CrossRefGoogle Scholar
  64. 64.
    Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101:1869–79.PubMedCrossRefGoogle Scholar
  65. 65.
    Thompson I. Market trends: disposable mono-dose auto-injectors and pen-injectors. ONdrugDelivery. 2008;15–17.Google Scholar
  66. 66.
    Young M. The next generation of auto-injectors. ONdrugDelivery. 2010:4–7.Google Scholar
  67. 67.
    Dey-Pharma. EpiPen Autoinjector. www.dey.com; www.epipen.com (accessed December 2010).
  68. 68.
    EMD Serono Inc. and Pfizer Inc. Rebif. www.rebif.com (accessed December 2010).
  69. 69.
    Amgen and Pfizer Inc. SureClick. www.enbrel.com (accessed December 2010).
  70. 70.
    Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov. 2004;3:785–96.PubMedCrossRefGoogle Scholar
  71. 71.
    Jia L, Wong H, Cerna C, Weitman SD. Effect of nanonization on absorption of 301029: ex vivo and in vivo pharmacokinetic correlations determined by liquid chromatography/mass spectrometry. Pharm Res. 2002;19:1091–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Liversidge GG, Cundy KC. Particle-size reduction for improvement of oral bioavailability of hydrophobic drugs.1. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm. 1995;125:91–7.CrossRefGoogle Scholar
  73. 73.
    Liversidge GG, Conzentino P. Drug particle-size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats. Int J Pharm. 1995;125:309–13.CrossRefGoogle Scholar
  74. 74.
    Kraft WK, Steiger B, Beussink D, Quiring JN, Fitzgerald N, Greenberg HE, et al. The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers. J Clin Pharmacol. 2004;44:67–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol Sci. 2009;30:592–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov. 2003;2:347–60.PubMedCrossRefGoogle Scholar
  77. 77.
    Qiu LY, Bae YH. Polymer architecture and drug delivery. Pharm Res. 2006;23:1–30.PubMedCrossRefGoogle Scholar
  78. 78.
    Win KY, Feng SS. In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D, L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation. Biomaterials. 2006;27:2285–91.PubMedCrossRefGoogle Scholar
  79. 79.
    Gryparis EC, Hatziapostolou M, Papadimitriou E, Avgoustakis K. Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells. Eur J Pharm Biopharm. 2007;67:1–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Bajpai AK, Shukla SK, Bhanu S, Kankane S. Responsive polymers in controlled drug delivery. Prog Polym Sci. 2008;33:1088–118.CrossRefGoogle Scholar
  81. 81.
    Frutos G, Prior-Cabanillas A, París R, Quijada-Garrido I. A novel controlled drug delivery system based on pH-responsive hydrogels included in soft gelatin capsules. Acta Biomater. 2010;6:4650–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Guo B-L, Gao Q-Y. Preparation and properties of a pH/temperature-responsive carboxymethyl chitosan/poly(N-isopropylacrylamide)semi-IPN hydrogel for oral delivery of drugs. Carbohydr Res. 2007;342:2416–22.PubMedCrossRefGoogle Scholar
  83. 83.
    Suedee R, Jantarat C, Lindner W, Viernstein H, Songkro S, Srichana T. Development of a pH-responsive drug delivery system for enantioselective-controlled delivery of racemic drugs. J Control Release. 2010;142:122–31.PubMedCrossRefGoogle Scholar
  84. 84.
    Zhang K, Wu XYXY. Temperature and pH-responsive polymeric composite membranes for controlled delivery of proteins and peptides. Biomaterials. 2004;25:5281–91.PubMedCrossRefGoogle Scholar
  85. 85.
    Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, et al. PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release. 2006;114:343–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Li H, Carter JD, LaBean TH. Nanofabrication by DNA self-assembly. Mater Today. 2009;12:24–32.CrossRefGoogle Scholar
  87. 87.
    Ozin GA, Hou K, Lotsch BV, Cademartiri L, Puzzo DP, Scotognella F, et al. Nanofabrication by self-assembly. Mater Today. 2009;12:12–23.CrossRefGoogle Scholar
  88. 88.
    Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60:1615–26.PubMedCrossRefGoogle Scholar
  89. 89.
    Shah P. Use of nanotechnologies for drug delivery. MRS Bull. 2006;31:894–9.CrossRefGoogle Scholar
  90. 90.
    Kaiser LR. The future of multihospital systems. Top Health Care Financ. 1992;18:32–45.PubMedGoogle Scholar
  91. 91.
    Anitua E, Sanchez M, Orive G, Andia I. Delivering growth factors for therapeutics. Trends Pharmacol Sci. 2008;29:37–41.PubMedCrossRefGoogle Scholar
  92. 92.
    Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83:835–70.PubMedGoogle Scholar
  93. 93.
    Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med. 2008;2:1–13.PubMedCrossRefGoogle Scholar
  94. 94.
    Wound Biotechnology, Department of Dermatology, School of Medicine, Boston University. Growth factors: their development and testing. http://www.bu.edu/woundbiotech/growthfactors/gfdevtest.html (accessed January 2011).
  95. 95.
    Alaoui-Ismaili MH, Falb D. Design of second generation therapeutic recombinant bone morphogenetic proteins. Cytokine Growth Factor Rev. 2009;20:501–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Fortier LA, Mohammed HO, Lust G, Nixon AJ. Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg. 2002;84:276–88.CrossRefGoogle Scholar
  97. 97.
    Silva EA, Mooney DJ. Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis. J Thromb Haemost. 2007;5:590–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Chen RR, Silva EA, Yuen WW, Mooney DJ. Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharm Res. 2007;24:258–64.PubMedCrossRefGoogle Scholar
  99. 99.
    Meinel L, Zoidis E, Zapf J, Hassa P, Hottiger MO, Auer JA, et al. Localized insulin-like growth factor I delivery to enhance new bone formation. Bone. 2003;33:660–72.PubMedCrossRefGoogle Scholar
  100. 100.
    Patel ZS, Young S, Tabata Y, Jansen JA, Wong ME, Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone. 2008;43:931–40.PubMedCrossRefGoogle Scholar
  101. 101.
    Holland TA, Tabata Y, Mikos AG. In vitro release of transforming growth factor-beta 1 from gelatin microparticles encapsulated in biodegradable, injectable oligo(poly(ethylene glycol) fumarate) hydrogels. J Control Release. 2003;91:299–313.PubMedCrossRefGoogle Scholar
  102. 102.
    Langer R, Tirrell DA. Designing materials for biology and medicine. Nature. 2004;428:487–92.PubMedCrossRefGoogle Scholar
  103. 103.
    Orive G, Gascon AR, Hernandez RM, Igartua M, Pedraz JL. Cell microencapsulation technology for biomedical purposes: novel insights and challenges. Trends Pharmacol Sci. 2003;24:207–10.PubMedCrossRefGoogle Scholar
  104. 104.
    Orive G, Hernandez RM, Gascon AR, Igartua M, Pedraz JL. Encapsulated cell technology: from research to market. Trends Biotechnol. 2002;20:382–7.PubMedCrossRefGoogle Scholar
  105. 105.
    Orive G, Hernandez RM, Gascon AR, Calafiore R, Chang TMS, de Vos P, et al. History, challenges and perspectives of cell microencapsulation. Trends Biotechnol. 2004;22:87–92.PubMedCrossRefGoogle Scholar
  106. 106.
    Murua A, Portero A, Orive G, Hernandez RM, de Castro M, Pedraz JL. Cell microencapsulation technology: towards clinical application. J Control Release. 2008;132:76–83.PubMedCrossRefGoogle Scholar
  107. 107.
    de Vos P, Andersson A, Tam SK, Faas MM, Hallé JP. Advances and barriers in mammalian cell encapsulation for treatment of diabetes. Immunol Endocr Metab Agents Med Chem. 2006;6:139–53.CrossRefGoogle Scholar
  108. 108.
    Sakai S, Hashimoto I, Kawakami K. Development of alginate-agarose subsievesize capsules for subsequent modification with a polyelectrolyte complex membrane. Biochem Eng J. 2006;30:76–81.CrossRefGoogle Scholar
  109. 109.
    Baruch L, Machluf M. Alginate-chitosan complex coacervation for cell encapsulation: effect on mechanical properties and on long-term viability. Biopolymers. 2006;82:570–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Wu TJ, Huang HH, Hsu YM, Lyu SR, Wang YJ. A novel method of encapsulating and cultivating adherent mammalian cells within collagen microcarriers. Biotechnol Bioeng. 2007;98:578–85.PubMedCrossRefGoogle Scholar
  111. 111.
    Chung C, Mesa J, Miller GJ, Randolph MA, Gill TJ, Burdick JA. Effects of auricular chondrocyte expansion on neocartilage formation in photocrosslinked hyaluronic acid networks. Tissue Eng. 2006;12:2665–73.PubMedCrossRefGoogle Scholar
  112. 112.
    Ferreira LS, Gerecht S, Fuller J, Shieh HF, Vunjak-Novakovic G, Langer R. Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. Biomaterials. 2007;28:2706–17.PubMedCrossRefGoogle Scholar
  113. 113.
    Black SP, Constantinidis I, Cui H, Tucker-Burden C, Weber CJ, Safley SA. Immune responses to an encapsulated allogeneic islet beta-cell line in diabetic NOD mice. Biochem Biophys Res Commun. 2006;340:236–43.PubMedCrossRefGoogle Scholar
  114. 114.
    Dufrane D, Goebbels RM, Saliez A, Guiot Y, Gianello P. Six-month survival of microencapsulated pig islets and alginate biocompatibility in primates: proof of concept. Transplantation. 2006;81:1345–53.PubMedCrossRefGoogle Scholar
  115. 115.
    Calafiore R, Basta G, Luca G, Lemmi A, Racanicchi L, Mancuso F, et al. Standard technical procedures for microencapsulation of human islets for graft into nonimmunosuppressed patients with type 1 diabetes mellitus. Transplant Proc. 2006;38:1156–7.PubMedCrossRefGoogle Scholar
  116. 116.
    Calafiore R, Basta G, Luca G, Lemmi A, Montanucci MP, Calabrese G, et al. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes - First two cases. Diab Care. 2006;29:137–8.CrossRefGoogle Scholar
  117. 117.
    Hong Y, Song HQ, Gong YH, Mao ZW, Gao CY, Shen JC. Covalently crosslinked chitosan hydrogel: properties of in vitro degradation and chondrocyte encapsulation. Acta Biomater. 2007;3:23–31.PubMedCrossRefGoogle Scholar
  118. 118.
    Inanc B, Elcin AE, Koc A, Balos K, Parlar A, Elcin YM. Encapsulation and osteoinduction of human periodontal ligament fibroblasts in chitosan-hydroxyapatite microspheres. J Biomed Mater Res A. 2007;82A:917–26.CrossRefGoogle Scholar
  119. 119.
    Sakai S, Hashimoto I, Kawakami K. Production of cell-enclosing hollow-core agarose microcapsules via jetting in water-immiscible liquid paraffin and formation of embryoid body-like spherical tissues from mouse ES cells enclosed within these microcapsules. Biotechnol Bioeng. 2008;99:235–43.PubMedCrossRefGoogle Scholar
  120. 120.
    Sakai S, Hashimoto I, Kawakami K. Agarose-gelatin conjugate for adherent cell-enclosing capsules. Biotechnol Lett. 2007;29:731–5.PubMedCrossRefGoogle Scholar
  121. 121.
    Emerich DF, Thanos CG, Goddard M, Skinner SJM, Geany MS, Bell WJ, et al. Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys. Neurobiol Dis. 2006;23:471–80.PubMedCrossRefGoogle Scholar
  122. 122.
    Kaigler D, Krebsbach PH, Wang Z, West ER, Horger K, Mooney DJ. Transplanted endothelial cells enhance orthotopic bone regeneration. J Dent Res. 2006;85:633–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Chang TMS. Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov. 2005;4:221–35.PubMedCrossRefGoogle Scholar
  124. 124.
    Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng. 2006;8:343–75.PubMedCrossRefGoogle Scholar
  125. 125.
    Chancellor MB, Yoshimura N, Pruchnic R, Huard J. Gene therapy strategies for urological dysfunction. Trends Mol Med. 2001;7:301–6.PubMedCrossRefGoogle Scholar
  126. 126.
    Adachi N, Pelinkovic D, Lee CW, Fu FH, Huard J. Gene therapy and the future of cartilage repair. Oper Tech Orthop. 2001;11:138–44.CrossRefGoogle Scholar
  127. 127.
    Wright VJ, Peng HR, Huard J. Muscle-based gene therapy and tissue engineering for the musculoskeletal system. Drug Discov Today. 2001;6:728–33.PubMedCrossRefGoogle Scholar
  128. 128.
    Huard J, Li Y, Peng HR, Fu FH. Gene therapy and tissue engineering for sports medicine. J Gene Med. 2003;5:93–108.PubMedCrossRefGoogle Scholar
  129. 129.
    Kimelman N, Pelled G, Helm GA, Huard J, Schwarz EM, Gazit D. Review: gene- and stem cell-based therapeutics for bone regeneration and repair. Tissue Eng. 2007;13:1135–50.PubMedCrossRefGoogle Scholar
  130. 130.
    Usas A, Huard J. Muscle-derived stem cells for tissue engineering and regenerative therapy. Biomaterials. 2007;28:5401–6.PubMedCrossRefGoogle Scholar
  131. 131.
    Sakai T, Ling Y, Payne TR, Huard J. The use of ex vivo gene transfer based on muscle-derived stem cells for cardiovascular medicine. Trends Cardiovasc Med. 2002;12:115–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Meinel L, Hofmann S, Betz O, Fajardo R, Merkle HP, Langer R, et al. Osteogenesis by human mesenchymal stem cells cultured on silk biomaterials: comparison of adenovirus mediated gene transfer and protein delivery of BMP-2. Biomaterials. 2006;27:4993–5002.PubMedCrossRefGoogle Scholar
  133. 133.
    Hosseinkhani H, Yamamoto M, Inatsugu Y, Hiraoka Y, Inoue S, Shimokawa H, et al. Enhanced ectopic bone formation using a combination of plasmid DNA impregnation into 3-D scaffold and bioreactor perfusion culture. Biomaterials. 2006;27:1387–98.PubMedCrossRefGoogle Scholar
  134. 134.
    Tirney S, Mattes CE, Yoshimura N, Yokayama T, Ozawa H, Tzeng E, et al. Nitric oxide synthase gene therapy for erectile dysfunction: comparison of plasmid, adenovirus, and adenovirus-transduced myoblast vectors. Mol Urol. 2001;5:37–43.PubMedCrossRefGoogle Scholar
  135. 135.
    Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K, et al. Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther. 2005;12:1171–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Nixon AJ, Haupt JL, Frisbie DD, Morisset SS, McIlwraith CW, Robbins PD, et al. Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy. Gene Ther. 2005;12:177–86.PubMedCrossRefGoogle Scholar
  137. 137.
    Steinert AF, Nöth U, Tuan RS. Concepts in gene therapy for cartilage repair. Inj Int J Care Injured. 2008;39:S97–S113.Google Scholar
  138. 138.
    Jo J, Tabata Y. Non-viral gene transfection technologies for genetic engineering of stem cells. Eur J Pharm Biopharm. 2008;68:90–104.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.3B’s Research Group—Biomaterials, Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering & Regenerative MedicineUniversity of MinhoGuimarãesPortugal
  2. 2.Institute for Biotechnology and BioengineeringPT Government Associated LaboratoryGuimarãesPortugal

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