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Nanomaterials in Pharmacology pp 389–412Cite as

Nanomedicine for the Treatment of Musculoskeletal Diseases

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The human adult skeletal system is comprised of 206 bones, along with a network of ligaments, tendons and cartilage. In addition to providing locomotion, the skeletal tissues serve as attachment sites for muscles and as protection for vital soft tissue organs. They harbor hematopoietic tissues (bone marrow) and act as a reservoir for calcium and phosphorus. Just as with any other organ systems, many pathological conditions are associated with musculoskeletal tissues, such as osteoporosis, arthritis, impaired fracture healing, and bone cancers, etc. These diseases affect many people, especially the geriatric population, resulting in pain, stiffness, loss of body function and even mortality. The health-related quality of life in patients with musculoskeletal diseases is significantly reduced, and the rising number of patients suffering from age-related musculoskeletal diseases can become a significant economic burden in an aging society.

To address this issue, many clinical interventions, ranging from new therapeutic treatments to novel surgical procedures, have been developed. Due to the inherent nature of the musculoskeletal system and its clinical relevance, extensive work has been done in the development of nanomaterials scaffolding and the local delivery of functional agents to improve bone repair/regeneration, osseointegration with orthopedic implants and prevention or treatment of postoperative infections. This is a rather crowded field with many high quality reviews being published (Tran and Webster. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(3): 336–351, 2009; Harvey et al. J Orthop Trauma 24(Suppl 1): S25–S30, 2010; Stylios et al. Injury 38(Suppl 1): S63–S74, 2007; Sato and Webster. Expert Rev Med Devices 1(1): 105–114, 2004; Webster and Ahn. Adv Biochem Eng Biotechnol 103: 275–308, 2007), which the readers are encouraged to explore. This chapter, however, will be mainly focused on several new directions in the field, especially on the use of nanomaterials as carriers to target therapeutic agents to the musculoskeletal lesions after systemic administration. In contrast to the local nanomaterial depot approach, of which the material design and drug release/activation are somewhat arbitrary, the systemically administered carriers would “seek out” its target and deliver the drugs according to the pathological conditions present.

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References

  1. Boskey AL, Posner AS (1984) Bone structure, composition, and mineralization. Orthop Clin North Am 15(4):597–612

    CAS  PubMed  Google Scholar 

  2. Shea JE, Miller SC (2005) Skeletal function and structure: implications for tissue-targeted therapeutics. Adv Drug Deliv Rev 57(7):945–957

    CAS  PubMed  Google Scholar 

  3. Harvey EJ, Henderson JE, Vengallatore ST (2010) Nanotechnology and bone healing. J Orthop Trauma 24(Suppl 1):S25–S30

    PubMed  Google Scholar 

  4. Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3(Suppl 3):S131–S139

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092:385–396

    CAS  PubMed  Google Scholar 

  6. Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145

    PubMed Central  CAS  PubMed  Google Scholar 

  7. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342

    CAS  PubMed  Google Scholar 

  8. Silver IA, Murrills RJ, Etherington DJ (1988) Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts. Exp Cell Res 175(2):266–276

    CAS  PubMed  Google Scholar 

  9. Delaisse JM et al (2003) Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities. Microsc Res Tech 61(6):504–513

    CAS  PubMed  Google Scholar 

  10. Anderson HC (2003) Matrix vesicles and calcification. Curr Rheumatol Rep 5(3):222–226

    PubMed  Google Scholar 

  11. Boyce BF, Xing L (2007) The RANKL/RANK/OPG pathway. Curr Osteoporos Rep 5(3):98–104

    PubMed  Google Scholar 

  12. Boyce BF, Xing L (2007) Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 9(Suppl 1):S1

    PubMed Central  PubMed  Google Scholar 

  13. Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473(2):139–146

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Takada J (2006) Application of anti-resorptive drugs for the treatment of osteoporosis. Nihon Rinsho 64(2):385–391

    PubMed  Google Scholar 

  15. Stepan JJ et al (2003) Mechanisms of action of antiresorptive therapies of postmenopausal osteoporosis. Endocr Regul 37(4):225–238

    CAS  PubMed  Google Scholar 

  16. Honig S, Rajapakse CS, Chang G (2013) Current treatment approaches to osteoporosis - 2013. Bull Hosp Jt Dis 71(3):184–188

    Google Scholar 

  17. Blahos J (2011) Current and future options for treatment of osteoporosis. Vnitr Lek 57(11):888–890

    CAS  PubMed  Google Scholar 

  18. Baron R, Hesse E (2012) Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab 97(2):311–325

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Donahue KE et al (2012) Drug therapy for rheumatoid arthritis in adults: an update. Agency for Healthcare Research and Quality, Rockville, MD

    Google Scholar 

  20. John M (2007) Drug therapy for rheumatoid arthritis: comparative effectiveness. In: Comparative effectiveness review summary guides for clinicians. Agency for Healthcare Research and Quality, Rockville, MD

    Google Scholar 

  21. Lima AL et al (2014) Recommendations for the treatment of osteomyelitis. Braz J Infect Dis 18:526

    PubMed  Google Scholar 

  22. Tran N, Webster TJ (2009) Nanotechnology for bone materials. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(3):336–351

    CAS  PubMed  Google Scholar 

  23. Stylios G, Wan T, Giannoudis P (2007) Present status and future potential of enhancing bone healing using nanotechnology. Injury 38(Suppl 1):S63–S74

    PubMed  Google Scholar 

  24. Sato M, Webster TJ (2004) Nanobiotechnology: implications for the future of nanotechnology in orthopedic applications. Expert Rev Med Devices 1(1):105–114

    CAS  PubMed  Google Scholar 

  25. Webster TJ, Ahn ES (2007) Nanostructured biomaterials for tissue engineering bone. Adv Biochem Eng Biotechnol 103:275–308

    CAS  PubMed  Google Scholar 

  26. Choy EH et al (2005) A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs. Ann Rheum Dis 64(9):1288–1293

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Ruggiero SL et al (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62(5):527–534

    PubMed  Google Scholar 

  28. McHorney CA et al (2007) The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates. Curr Med Res Opin 23(12):3137–3152

    CAS  PubMed  Google Scholar 

  29. Uzawa T et al (1995) Comparison of the effects of intermittent and continuous administration of human parathyroid hormone(1-34) on rat bone. Bone 16(4):477–484

    CAS  PubMed  Google Scholar 

  30. Lotinun S, Sibonga JD, Turner RT (2002) Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression. Endocrine 17(1):29–36

    CAS  PubMed  Google Scholar 

  31. de Ligny CL et al (1990) Bone seeking pharmaceuticals. Int J Rad Appl Instrum B 17(2):161–179

    PubMed  Google Scholar 

  32. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18(2):75–85

    CAS  PubMed  Google Scholar 

  33. Hengst V et al (2007) Bone targeting potential of bisphosphonate-targeted liposomes. Preparation, characterization and hydroxyapatite binding in vitro. Int J Pharm 331(2):224–227

    CAS  PubMed  Google Scholar 

  34. El-Mabhouh AA et al (2011) A conjugate of gemcitabine with bisphosphonate (Gem/BP) shows potential as a targeted bone-specific therapeutic agent in an animal model of human breast cancer bone metastases. Oncol Res 19(6):287–295

    CAS  PubMed  Google Scholar 

  35. El-Mabhouh AA, Mercer JR (2008) 188Re-labelled gemcitabine/bisphosphonate (Gem/BP): a multi-functional, bone-specific agent as a potential treatment for bone metastases. Eur J Nucl Med Mol Imaging 35(7):1240–1248

    CAS  PubMed  Google Scholar 

  36. El-Mabhouh AA et al (2006) A 99mTc-labeled gemcitabine bisphosphonate drug conjugate as a probe to assess the potential for targeted chemotherapy of metastatic bone cancer. Nucl Med Biol 33(6):715–722

    CAS  PubMed  Google Scholar 

  37. Allen MR, Ruggiero SL (2014) A review of pharmaceutical agents and oral bone health: how osteonecrosis of the jaw has affected the field. Int J Oral Maxillofac Implants 29(1):e45–e57

    PubMed  Google Scholar 

  38. Ryan P, Saleh I, Stassen LF (2009) Osteonecrosis of the jaw: a rare and devastating side effect of bisphosphonates. Postgrad Med J 85(1010):674–677

    CAS  PubMed  Google Scholar 

  39. Kasugai S et al (2000) Selective drug delivery system to bone: small peptide (Asp)6 conjugation. J Bone Miner Res 15(5):936–943

    CAS  PubMed  Google Scholar 

  40. Takahashi-Nishioka T et al (2008) Targeted drug delivery to bone: pharmacokinetic and pharmacological properties of acidic oligopeptide-tagged drugs. Curr Drug Discov Technol 5(1):39–48

    CAS  PubMed  Google Scholar 

  41. Sekido T et al (2001) Novel drug delivery system to bone using acidic oligopeptide: pharmacokinetic characteristics and pharmacological potential. J Drug Target 9(2):111–121

    CAS  PubMed  Google Scholar 

  42. Takahashi T et al (2008) Bone-targeting of quinolones conjugated with an acidic oligopeptide. Pharm Res 25(12):2881–2888

    CAS  PubMed  Google Scholar 

  43. Nishioka T et al (2006) Enhancement of drug delivery to bone: characterization of human tissue-nonspecific alkaline phosphatase tagged with an acidic oligopeptide. Mol Genet Metab 88(3):244–255

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Pierce WM Jr, Waite LC (1987) Bone-targeted carbonic anhydrase inhibitors: effect of a proinhibitor on bone resorption in vitro. Proc Soc Exp Biol Med 186(1):96–102

    CAS  PubMed  Google Scholar 

  45. Neale JR et al (2009) Bone selective effect of an estradiol conjugate with a novel tetracycline-derived bone-targeting agent. Bioorg Med Chem Lett 19(3):680–683

    CAS  PubMed  Google Scholar 

  46. Thompson WJ, Thompson DD, Anderson PS, Rodan GA (1989) Polymalonic acids as boneaffinity agents. EP 0341961

    Google Scholar 

  47. Shimoda Y et al (1994) Calcium ion binding of three different types of oligo/polysialic acids as studied by equilibrium dialysis and circular dichroic methods. Biochemistry 33(5):1202–1208

    CAS  PubMed  Google Scholar 

  48. Segal E et al (2009) Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS One 4(4):e5233

    PubMed Central  PubMed  Google Scholar 

  49. Choi SW, Kim JH (2007) Design of surface-modified poly(D, L-lactide-co-glycolide) nanoparticles for targeted drug delivery to bone. J Control Release 122(1):24–30

    CAS  PubMed  Google Scholar 

  50. Pan H et al (2006) Water-soluble HPMA copolymer--prostaglandin E1 conjugates containing a cathepsin K sensitive spacer. J Drug Target 14(6):425–435

    CAS  PubMed  Google Scholar 

  51. Henson PM (2005) Dampening inflammation. Nat Immunol 6(12):1179–1181

    CAS  PubMed  Google Scholar 

  52. Yuan F et al (2012) Development of macromolecular prodrug for rheumatoid arthritis. Adv Drug Deliv Rev 64(12):1205–1219

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Ren K et al (2014) Early diagnosis of orthopedic implant failure using macromolecular imaging agents. Pharm Res 31:2086

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Purdue PE et al (2013) Development of polymeric nanocarrier system for early detection and targeted therapeutic treatment of peri-implant osteolysis. HSS J 9(1):79–85

    PubMed Central  PubMed  Google Scholar 

  55. Ren K et al (2014) Macromolecular prodrug of dexamethasone prevents particle-induced peri-implant osteolysis with reduced systemic side effects. J Control Release 175:1–9

    PubMed Central  CAS  PubMed  Google Scholar 

  56. Centers for Disease Control and Prevention (2009) Prevalence and most common causes of disability among adults—United States, 2005. MMWR Morb Mortal Wkly Rep 58:421–426

    Google Scholar 

  57. Quan LD et al (2008) The development of novel therapies for rheumatoid arthritis. Expert Opin Ther Pat 18(7):723–738

    PubMed Central  CAS  PubMed  Google Scholar 

  58. Tarner IH, Muller-Ladner U (2008) Drug delivery systems for the treatment of rheumatoid arthritis. Expert Opin Drug Deliv 5(9):1027–1037

    CAS  PubMed  Google Scholar 

  59. Metselaar JM et al (2003) Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis Rheum 48(7):2059–2066

    CAS  PubMed  Google Scholar 

  60. Khoury M et al (2006) Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor alpha in experimental arthritis. Arthritis Rheum 54(6):1867–1877

    CAS  PubMed  Google Scholar 

  61. Koning GA et al (2006) Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate-containing RGD peptide liposomes inhibits experimental arthritis. Arthritis Rheum 54(4):1198–1208

    CAS  PubMed  Google Scholar 

  62. Gaspar MM et al (2007) Enzymosomes with surface-exposed superoxide dismutase: in vivo behaviour and therapeutic activity in a model of adjuvant arthritis. J Control Release 117(2):186–195

    CAS  PubMed  Google Scholar 

  63. Kapoor B et al (2014) Application of liposomes in treatment of rheumatoid arthritis: quo vadis. ScientificWorldJournal 2014:978351

    PubMed Central  PubMed  Google Scholar 

  64. Vanniasinghe AS, Bender V, Manolios N (2009) The potential of liposomal drug delivery for the treatment of inflammatory arthritis. Semin Arthritis Rheum 39(3):182–196

    CAS  PubMed  Google Scholar 

  65. van den Hoven JM et al (2011) Liposomal drug formulations in the treatment of rheumatoid arthritis. Mol Pharm 8(4):1002–1015

    PubMed  Google Scholar 

  66. Metselaar JM et al (2004) Liposomal targeting of glucocorticoids to synovial lining cells strongly increases therapeutic benefit in collagen type II arthritis. Ann Rheum Dis 63(4):348–353

    PubMed Central  CAS  PubMed  Google Scholar 

  67. Avnir Y et al (2008) Amphipathic weak acid glucocorticoid prodrugs remote-loaded into sterically stabilized nanoliposomes evaluated in arthritic rats and in a Beagle dog: a novel approach to treating autoimmune arthritis. Arthritis Rheum 58(1):119–129

    CAS  PubMed  Google Scholar 

  68. Danhier F et al (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161(2):505–522

    CAS  PubMed  Google Scholar 

  69. Higaki M et al (2005) Treatment of experimental arthritis with poly(D, L-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate. Ann Rheum Dis 64(8):1132–1136

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Ishihara T et al (2009) Treatment of experimental arthritis with stealth-type polymeric nanoparticles encapsulating betamethasone phosphate. J Pharmacol Exp Ther 329(2):412–417

    CAS  PubMed  Google Scholar 

  71. Crielaard BJ et al (2012) Glucocorticoid-loaded core-cross-linked polymeric micelles with tailorable release kinetics for targeted therapy of rheumatoid arthritis. Angew Chem Int Ed Engl 51(29):7254–7258

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Wilson DR et al (2014) Synthesis and evaluation of cyclosporine A-loaded polysialic acid-polycaprolactone micelles for rheumatoid arthritis. Eur J Pharm Sci 51:146–156

    CAS  PubMed  Google Scholar 

  73. Quan L et al (2014) Nanomedicines for inflammatory arthritis: head-to-head comparison of glucocorticoid-containing polymers, micelles, and liposomes. ACS Nano 8(1):458–466

    PubMed Central  CAS  PubMed  Google Scholar 

  74. Liu XM et al (2008) Synthesis and evaluation of a well-defined HPMA copolymer-dexamethasone conjugate for effective treatment of rheumatoid arthritis. Pharm Res 25(12):2910–2919

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Quan LD et al (2010) Development of a macromolecular prodrug for the treatment of inflammatory arthritis: mechanisms involved in arthrotropism and sustained therapeutic efficacy. Arthritis Res Ther 12(5):R170

    PubMed Central  PubMed  Google Scholar 

  76. Liu XM et al (2010) Syntheses of click PEG-dexamethasone conjugates for the treatment of rheumatoid arthritis. Biomacromolecules 11(10):2621–2628

    PubMed Central  CAS  PubMed  Google Scholar 

  77. Wang D et al (2002) Inhibition of cathepsin K with lysosomotropic macromolecular inhibitors. Biochemistry 41(28):8849–8859

    CAS  PubMed  Google Scholar 

  78. Lawrence RC et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 58(1):26–35

    PubMed Central  PubMed  Google Scholar 

  79. Felson DT (2014) Osteoarthritis: priorities for osteoarthritis research: much to be done. Nat Rev Rheumatol 10:447

    PubMed  Google Scholar 

  80. Gerwin N, Hops C, Lucke A (2006) Intraarticular drug delivery in osteoarthritis. Adv Drug Deliv Rev 58(2):226–242

    CAS  PubMed  Google Scholar 

  81. Hinton R et al (2002) Osteoarthritis: diagnosis and therapeutic considerations. Am Fam Physician 65(5):841–848

    PubMed  Google Scholar 

  82. Hochberg MC et al (1995) Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum 38(11):1541–1546

    CAS  PubMed  Google Scholar 

  83. George E (1998) Intra-articular hyaluronan treatment for osteoarthritis. Ann Rheum Dis 57(11):637–640

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Dingle JT et al (1978) Novel treatment for joint inflammation. Nature 271(5643):372–373

    CAS  PubMed  Google Scholar 

  85. Foong WC, Green KL (1988) Retention and distribution of liposome-entrapped [3H]methotrexate injected into normal or arthritic rabbit joints. J Pharm Pharmacol 40(7):464–468

    CAS  PubMed  Google Scholar 

  86. Holland TA, Mikos AG (2003) Advances in drug delivery for articular cartilage. J Control Release 86(1):1–14

    CAS  PubMed  Google Scholar 

  87. Ratcliffe JH et al (1987) Albumin microspheres for intra-articular drug delivery: investigation of their retention in normal and arthritic knee joints of rabbits. J Pharm Pharmacol 39(4):290–295

    CAS  PubMed  Google Scholar 

  88. Horisawa E et al (2002) Prolonged anti-inflammatory action of DL-lactide/glycolide copolymer nanospheres containing betamethasone sodium phosphate for an intra-articular delivery system in antigen-induced arthritic rabbit. Pharm Res 19(4):403–410

    CAS  PubMed  Google Scholar 

  89. Brown KE et al (1998) Gelatin/chondroitin 6-sulfate microspheres for the delivery of therapeutic proteins to the joint. Arthritis Rheum 41(12):2185–2195

    CAS  PubMed  Google Scholar 

  90. Iwasaki M, Soh M, Kaneko H (1991) Diagnosis, treatment and prophylaxis of catheter related sepsis. Nihon Rinsho 49(Suppl):182–187

    PubMed  Google Scholar 

  91. Holroyd C, Cooper C, Dennison E (2008) Epidemiology of osteoporosis. Best Pract Res Clin Endocrinol Metab 22(5):671–685

    PubMed  Google Scholar 

  92. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22:465–475

    Google Scholar 

  93. Cenni E et al (2008) Biocompatibility of poly(D, L-lactide-co-glycolide) nanoparticles conjugated with alendronate. Biomaterials 29(10):1400–1411

    CAS  PubMed  Google Scholar 

  94. Pignatello R et al (2009) A novel biomaterial for osteotropic drug nanocarriers: synthesis and biocompatibility evaluation of a PLGA-ALE conjugate. Nanomedicine (Lond) 4(2):161–175

    CAS  Google Scholar 

  95. Wang D et al (2006) Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers. Mol Pharm 3(6):717–725

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Zhang G et al (2012) A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med 18(2):307–314

    PubMed  Google Scholar 

  97. Sang Yoo H, Gwan Park T (2004) Biodegradable nanoparticles containing protein-fatty acid complexes for oral delivery of salmon calcitonin. J Pharm Sci 93(2):488–495

    PubMed  Google Scholar 

  98. Narayanan D et al (2013) In vitro and in vivo evaluation of osteoporosis therapeutic peptide PTH 1-34 loaded PEGylated chitosan nanoparticles. Mol Pharm 10(11):4159–4167

    CAS  PubMed  Google Scholar 

  99. Takeuchi H et al (2003) Mucoadhesive properties of carbopol or chitosan-coated liposomes and their effectiveness in the oral administration of calcitonin to rats. J Control Release 86(2-3):235–242

    CAS  PubMed  Google Scholar 

  100. Lamprecht A et al (2004) pH-sensitive microsphere delivery increases oral bioavailability of calcitonin. J Control Release 98(1):1–9

    CAS  PubMed  Google Scholar 

  101. Narayanan D et al (2014) PTH 1-34 loaded thiolated chitosan nanoparticles for osteoporosis: oral bioavailability and anabolic effect on primary osteoblast cells. J Biomed Nanotechnol 10(1):166–178

    CAS  PubMed  Google Scholar 

  102. Saini D, Fazil M, Ali MM, Baboota S, Ali J (2015) Formulation, development and optimization of raloxifeneloaded chitosan nanoparticles for treatment of osteoporosis. Drug Deliv 22:1–14. [Epub ahead of print]

    Google Scholar 

  103. Fazil M et al (2013) Exploring drug delivery systems for treating osteoporosis. Expert Opin Drug Deliv 10(8):1123–1136

    CAS  PubMed  Google Scholar 

  104. Low SA, Kopecek J (2012) Targeting polymer therapeutics to bone. Adv Drug Deliv Rev 64(12):1189–1204

    PubMed Central  CAS  PubMed  Google Scholar 

  105. Society AC (2008) Cancer facts and figures 2008. American Cancer Society. Retrieved on March 13, 2008

    Google Scholar 

  106. Hughes DP (2009) Strategies for the targeted delivery of therapeutics for osteosarcoma. Expert Opin Drug Deliv 6(12):1311–1321

    PubMed Central  CAS  PubMed  Google Scholar 

  107. Gabizon A, Martin F (1997) Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours. Drugs 54(Suppl 4):15–21

    CAS  PubMed  Google Scholar 

  108. Alberts DS, Garcia DJ (1997) Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Drugs 54(Suppl 4):30–35

    CAS  PubMed  Google Scholar 

  109. Skubitz KM (2003) Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. Cancer Invest 21(2):167–176

    CAS  PubMed  Google Scholar 

  110. Judson I et al (2001) Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 37(7):870–877

    CAS  PubMed  Google Scholar 

  111. Kamba SA et al (2013) In vitro delivery and controlled release of Doxorubicin for targeting osteosarcoma bone cancer. Molecules 18(9):10580–10598

    CAS  PubMed  Google Scholar 

  112. Susa M et al (2009) Doxorubicin loaded Polymeric Nanoparticulate Delivery System to overcome drug resistance in osteosarcoma. BMC Cancer 9:399

    PubMed Central  PubMed  Google Scholar 

  113. Federman N et al (2012) Enhanced growth inhibition of osteosarcoma by cytotoxic polymerized liposomal nanoparticles targeting the alcam cell surface receptor. Sarcoma 2012:126906

    PubMed Central  PubMed  Google Scholar 

  114. Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12(20 Pt 2):6243s–6249s

    PubMed  Google Scholar 

  115. Guise T (2010) Examining the metastatic niche: targeting the microenvironment. Semin Oncol 37(Suppl 2):S2–S14

    CAS  PubMed  Google Scholar 

  116. Clezardin P, Benzaid I, Croucher PI (2011) Bisphosphonates in preclinical bone oncology. Bone 49(1):66–70

    CAS  PubMed  Google Scholar 

  117. Coleman R (2011) The use of bisphosphonates in cancer treatment. Ann N Y Acad Sci 1218:3–14

    CAS  PubMed  Google Scholar 

  118. Gnant M (2009) Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. Curr Cancer Drug Targets 9(7):824–833

    CAS  PubMed  Google Scholar 

  119. Coleman RE, McCloskey EV (2011) Bisphosphonates in oncology. Bone 49(1):71–76

    CAS  PubMed  Google Scholar 

  120. Ramanlal Chaudhari K et al (2012) Bone metastasis targeting: a novel approach to reach bone using Zoledronate anchored PLGA nanoparticle as carrier system loaded with Docetaxel. J Control Release 158(3):470–478

    CAS  PubMed  Google Scholar 

  121. Miller K et al (2009) Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate. Angew Chem Int Ed Engl 48(16):2949–2954

    CAS  PubMed  Google Scholar 

  122. Miller K et al (2011) Antiangiogenic antitumor activity of HPMA copolymer-paclitaxel-alendronate conjugate on breast cancer bone metastasis mouse model. Mol Pharm 8(4):1052–1062

    CAS  PubMed  Google Scholar 

  123. Daubine F et al (2009) Nanostructured polyelectrolyte multilayer drug delivery systems for bone metastasis prevention. Biomaterials 30(31):6367–6373

    CAS  PubMed  Google Scholar 

  124. Wang D et al (2007) Osteotropic Peptide that differentiates functional domains of the skeleton. Bioconjug Chem 18(5):1375–1378

    CAS  PubMed  Google Scholar 

  125. Gogia JS et al (2009) Local antibiotic therapy in osteomyelitis. Semin Plast Surg 23(2):100–107

    PubMed Central  PubMed  Google Scholar 

  126. Diana Gomes MP, Bettencourt AF (2013) Osteomyelitis: an overview of antimicrobial therapy. Braz J Pharm Sci 49(1):13–27

    Google Scholar 

  127. Verhelle N et al (2003) How to deal with bone exposure and osteomyelitis: an overview. Acta Orthop Belg 69(6):481–494

    PubMed  Google Scholar 

  128. Lang S (1996) Osteomyelitis. A pathomorphologic overview. Radiologe 36(10):781–785

    CAS  PubMed  Google Scholar 

  129. Mouzopoulos G et al (2011) Management of bone infections in adults: the surgeon’s and microbiologist’s perspectives. Injury 42(Suppl 5):S18–S23

    PubMed  Google Scholar 

  130. Kanellakopoulou K, Giamarellos-Bourboulis EJ (2000) Carrier systems for the local delivery of antibiotics in bone infections. Drugs 59(6):1223–1232

    CAS  PubMed  Google Scholar 

  131. Holtom PD, Patzakis MJ (2003) Newer methods of antimicrobial delivery for bone and joint infections. Instr Course Lect 52:745–749

    PubMed  Google Scholar 

  132. Nelson CL et al (1992) In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads. Clin Orthop Relat Res 284:303–309

    PubMed  Google Scholar 

  133. Mader JT, Calhoun J, Cobos J (1997) In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads. Antimicrob Agents Chemother 41(2):415–418

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Gitelis S, Brebach GT (2002) The treatment of chronic osteomyelitis with a biodegradable antibiotic-impregnated implant. J Orthop Surg (Hong Kong) 10(1):53–60

    Google Scholar 

  135. Desai TA, Uskokovic V (2013) Calcium phosphate nanoparticles: a future therapeutic platform for the treatment of osteomyelitis? Ther Deliv 4(6):643–645

    PubMed Central  CAS  PubMed  Google Scholar 

  136. Singh N et al (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30(23-24):3891–3914

    CAS  PubMed  Google Scholar 

  137. Uskokovic V, Desai TA (2013) Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. II. Antibacterial and osteoblastic response. J Biomed Mater Res A 101(5):1427–1436

    PubMed Central  PubMed  Google Scholar 

  138. Uskokovic V, Desai TA (2013) Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release. J Biomed Mater Res A 101(5):1416–1426

    PubMed Central  PubMed  Google Scholar 

  139. Uskokovic V et al (2013) Effect of calcium phosphate particle shape and size on their antibacterial and osteogenic activity in the delivery of antibiotics in vitro. ACS Appl Mater Interfaces 5(7):2422–2431

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Uskokovic V et al (2013) Osteogenic and antimicrobial nanoparticulate calcium phosphate and poly-(D, L-lactide-co-glycolide) powders for the treatment of osteomyelitis. Mater Sci Eng C Mater Biol Appl 33(6):3362–3373

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Fang T et al (2012) Poly (epsilon-caprolactone) coating delays vancomycin delivery from porous chitosan/beta-tricalcium phosphate composites. J Biomed Mater Res B Appl Biomater 100(7):1803–1811

    PubMed  Google Scholar 

  142. Samit Kumar Nandi PM, Roy S, Kundu B, De Kumar D, Basu D (2009) Local antibiotic delivery systems for the treatment of osteomyelitis – a review. Mater Sci Eng C 29(8):2478–2485

    Google Scholar 

  143. Oldham JB et al (2000) Biological activity of rhBMP-2 released from PLGA microspheres. J Biomech Eng 122(3):289–292

    CAS  PubMed  Google Scholar 

  144. Cao L et al (2014) Vascularization and bone regeneration in a critical sized defect using 2-N,6-O-sulfated chitosan nanoparticles incorporating BMP-2. Biomaterials 35(2):684–698

    CAS  PubMed  Google Scholar 

  145. Raftery R, O’Brien FJ, Cryan SA (2013) Chitosan for gene delivery and orthopedic tissue engineering applications. Molecules 18(5):5611–5647

    CAS  PubMed  Google Scholar 

  146. Gentile P et al (2014) An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci 15(3):3640–3659

    PubMed Central  CAS  PubMed  Google Scholar 

  147. Puppi D et al (2011) Optimized electro- and wet-spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite. J Tissue Eng Regen Med 5(4):253–263

    CAS  PubMed  Google Scholar 

  148. Nie H, Wang CH (2007) Fabrication and characterization of PLGA/HAp composite scaffolds for delivery of BMP-2 plasmid DNA. J Control Release 120(1-2):111–121

    CAS  PubMed  Google Scholar 

  149. Mouthuy PA et al (2010) Physico-chemical characterization of functional electrospun scaffolds for bone and cartilage tissue engineering. Proc Inst Mech Eng H 224(12):1401–1414

    CAS  PubMed  Google Scholar 

  150. Lin G et al (2012) Injectable and thermosensitive PLGA-g-PEG hydrogels containing hydroxyapatite: preparation, characterization and in vitro release behavior. Biomed Mater 7(2):024107

    PubMed  Google Scholar 

  151. Lee TJ et al (2010) Apatite-coated porous poly(lactic-co-glycolic acid) microspheres as an injectable bone substitute. J Biomater Sci Polym Ed 21(5):635–645

    CAS  PubMed  Google Scholar 

  152. Shi X et al (2009) Enhancing alendronate release from a novel PLGA/hydroxyapatite microspheric system for bone repairing applications. Pharm Res 26(2):422–430

    CAS  PubMed  Google Scholar 

  153. Wang Q et al (2013) Hybrid hydroxyapatite nanoparticle colloidal gels are injectable fillers for bone tissue engineering. Tissue Eng Part A 19(23-24):2586–2593

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Yao Y, Shi X, Chen F (2014) The effect of gold nanoparticles on the proliferation and differentiation of murine osteoblast: a study of MC3T3-E1 cells in vitro. J Nanosci Nanotechnol 14(7):4851–4857

    CAS  PubMed  Google Scholar 

  155. Rose FR, Hou Q, Oreffo RO (2004) Delivery systems for bone growth factors - the new players in skeletal regeneration. J Pharm Pharmacol 56(4):415–427

    CAS  PubMed  Google Scholar 

  156. Nguyen LT, Min YK, Lee BT (2015) Nanoparticle biphasic calcium phosphate loading on gelatin-pectin scaffold for improved bone regeneration. Tissue Eng Part A 21:1376

    CAS  PubMed  Google Scholar 

  157. Hu J et al (2014) Effect of nano-hydroxyapatite coating on the osteoinductivity of porous biphasic calcium phosphate ceramics. BMC Musculoskelet Disord 15:114

    PubMed Central  PubMed  Google Scholar 

  158. Kawazoe N, Chen G, Tateishi T (2008) Development of novel biomaterials for bone and cartilage tissue engineering. Clin Calcium 18(12):1713–1720

    CAS  PubMed  Google Scholar 

  159. Zhou YN, Xia LG, Xu YJ (2014) Research progress of nano-hydroxyapatite complexes in bone tissue regeneration. Shanghai Kou Qiang Yi Xue 23(2):248–252

    PubMed  Google Scholar 

  160. Matassi F et al (2011) New biomaterials for bone regeneration. Clin Cases Miner Bone Metab 8(1):21–24

    PubMed Central  PubMed  Google Scholar 

  161. Perez-Sanchez MJ et al (2010) Biomaterials for bone regeneration. Med Oral Patol Oral Cir Bucal 15(3):e517–e522

    PubMed  Google Scholar 

  162. Allo BA et al (2012) Bioactive and biodegradable nanocomposites and hybrid biomaterials for bone regeneration. J Funct Biomater 3(2):432–463

    PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, COP 3026, 986025 Nebraska Medical Center, Omaha, NE, 68198-6025, USA

    Ke Ren, Xin Wei & Dong Wang Ph.D.

  2. Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 69198, USA

    Lingli Zhang

  3. West China Second University Hospital, Sichuan University, No. 20, Third Section, Renmin Nan Lu, Chengdu, Sichuan, 610041, P. R. China

    Lingli Zhang

Authors
  1. Ke Ren
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  2. Xin Wei
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  3. Lingli Zhang
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  4. Dong Wang Ph.D.
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Corresponding author

Correspondence to Dong Wang Ph.D. .

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Editors and Affiliations

  1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA

    Zheng-Rong Lu

  2. Laboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan

    Shinji Sakuma

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Ren, K., Wei, X., Zhang, L., Wang, D. (2016). Nanomedicine for the Treatment of Musculoskeletal Diseases. In: Lu, ZR., Sakuma, S. (eds) Nanomaterials in Pharmacology. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3121-7_20

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  • DOI: https://doi.org/10.1007/978-1-4939-3121-7_20

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3120-0

  • Online ISBN: 978-1-4939-3121-7

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